At a glance
What is it—and why does it matter?
Orforglipron is an oral small-molecule (non-peptide) GLP-1 receptor agonist. Orforglipron activates the GLP-1 receptor (it is a GLP-1 receptor agonist). In adults with obesity without diabetes, taking orforglipron once daily for 72 weeks reduced body weight more than placebo. After a single 0.3 to 6 mg dose, the mean half-life was 24.6 to 35.3 hours.
Sources for this introduction: [1] [2] [3] [4]
This published profile is a reference in progress. Findings retain their source context; missing topics are marked below.
Simple guide
Orforglipron, in plain English
The main points from the published research. Each one links to the source it comes from.
What it is
Orforglipron is a small-molecule, once-daily, oral, non-peptide GLP-1 receptor agonist.
Source for this finding
“Orforglipron is a novel small-molecule, once daily oral non-peptide GLP-1 receptor agonist.”
Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials.
What the research looks like
Most published findings come from studies in people.
- 93 People 71%
- 6 Animals or lab 5%
- 32 Other or unclear 24%
Counts show where findings come from, not how strong they are. Animal and lab findings are counted together because study types have not been labelled for this profile yet.
What studies in people found
With 12 mg, the estimated treatment difference vs placebo at week 72 was -4·5 (95% CI -5·5 to -3·6); p<0·0001.
Source for this finding
With 6 mg, the estimated treatment difference vs placebo at week 72 was -2·7 (95% CI -3·7 to -1·6); p<0·0001.
Source for this finding
“estimated treatment difference [ETD] -2·7 [95% CI -3·7 to -1·6]; p<0·0001”
Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial.For HbA1c at week 40, each orforglipron dose was superior to placebo: treatment differences were -0.78% (3 mg), -1.08% (12 mg), and -1.03% (36 mg), with P < .001 for all.
Source for this finding
“Each dosage of orforglipron was superior to placebo (estimated treatment differences: 3 mg once daily, -0.78% [95% CI, -1.02% to -0.55%]; 12 mg once daily, -1.08% [95% CI, -1.33% to -0.83%]; 36 mg once daily, -1.03% [95% CI, -1.28% to -0.77%]; P < .001 for all).”
Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial.Comparators included placebo, oral semaglutide, dapagliflozin, and insulin glargine.
Source for this finding
“pooled comparator [placebo, oral semaglutide, dapagliflozin, insulin glargine]”
Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials.The conclusion states orforglipron and high-dose oral semaglutide had the most consistent, substantial weight reductions, but comparisons are limited by low-to-moderate certainty and no head-to-head trials.
Source for this finding
“HiD oral semaglutide and orforglipron demonstrated the most consistent and substantial weight reductions though low-to-moderate certainty and lack of head-to-head comparisons constrain comparative inference.”
Role of Oral Glucagon-Like Peptide-1 Receptor Agonists in Weight Management for Individuals With Overweight or Obesity Without Diabetes: A Network Meta-Analysis of Randomized Controlled Trials.
What animal and lab studies suggest
Not proven in people. Results in animals or cells often do not hold up in humans.
In diet-induced obese Glp1rS33W rats, oral orforglipron was associated with weight loss versus subcutaneous semaglutide.
Source for this finding
“Diet-induced obesity inGlp1rS33Wrats enabled studies showing weight loss in animals orally administered orforglipron versus subcutaneous injection of GLP-1R agonist semaglutide.”
The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron.In a human microglial cell line, orforglipron reduced LPS- and glutamate-induced secretion of IL-6, IL-8, and MCP-1.
Source for this finding
“Additionally, orforglipron effectively mitigated LPS- and glutamate-induced proinflammatory protein secretion (IL-6, IL-8, and MCP-1) from a human microglial cell line.”
Orforglipron, a Small-Molecule Glucagon-like Peptide-1 Receptor Agonist (GLP-1RA), Has Neuroprotective and Anti-Inflammatory Effects.In mice with human GLP-1R, low receptor occupancy by orforglipron was enough to produce a full biological response.
Source for this finding
“These experiments revealed that low GLP-1R occupancy by orforglipron is sufficient to yield a full biological response.”
The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron.
Safety
No safety findings are published in this profile yet. Missing safety data does not mean it is safe.
What we don't know
- Not yet covered in this profile: administration, contraindications, interactions, regulatory status, safety.
A missing finding does not mean something is safe or effective.
See all 154 findings and sourcesEvery finding, grouped by topic, with its exact source passages
What is it?
A molecule, not a product name.
Identity
Orforglipron is a small-molecule, once-daily, oral, non-peptide GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron is a novel small-molecule, once daily oral non-peptide GLP-1 receptor agonist.”
Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials. · AIMS
Identity
Orforglipron is an orally bioavailable small-molecule medicine.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron is a small molecule orally bioavailable medicine”
The role of GLP-1 and GIP receptor agonists in the treatment of diabetes and obesity. · Abstract
Identity
Orforglipron is described as the first non-peptide oral GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“This medication class now includes oral formulations including oral semaglutide and the first non-peptide oral GLP-1RA, orforglipron”
Integrating glucagon-like peptide-1 receptor agonists into dermatology practice: Safety and monitoring strategies. · Abstract
Identity
Orforglipron is a small-molecule (non-peptide) GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“true small-molecule, non-peptide GLP-1 receptor agonists (e.g., orforglipron)”
Small-Molecule Oral Versus Injectable Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists: Comparative Efficacy, Safety, and Future Clinical Perspectives. · Abstract
Identity
Orforglipron (LY3502970) is an oral, non-peptide GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“orforglipron (LY3502970), an oral, non‐peptide glucagon‐like peptide‐1 receptor agonist (GLP‐1RA)”
Orforglipron ( <scp>LY3502970</scp> ), a novel, oral non‐peptide glucagon‐like peptide‐1 receptor agonist: A Phase 1a, blinded, placebo‐controlled, randomized, single‐ and multiple‐ascending‐dose study in healthy participants · Abstract
Identity
Orforglipron is a once-daily oral, nonpeptide GLP-1 receptor agonist.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron, a once-daily oral nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist”
Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. · Abstract
Identity
Orforglipron is an oral, nonpeptide small-molecule GLP-1 receptor agonist developed for type 2 diabetes and obesity.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron is an oral, nonpeptide, small-molecule glucagon-like peptide-1 receptor agonist developed for type 2 diabetes and obesity.”
Comparative Positioning of Orforglipron Among Selected GLP-1 Receptor Agonist Benchmarks: A Narrative Review. · Abstract
Identity
Orforglipron is a non-peptidyl oral GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Non-peptidyl oral GLP-1 RAs such as orforglipron, offer novel formulation strategies to enhance treatment accessibility and adherence.”
Engineered nutrient-stimulated hormonal multi-agonists for precision targeting of obesity and metabolic disorders. · Abstract
Identity
Orforglipron is an oral GLP-1 agonist mentioned in this review.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Oral GLP-1 agonists, including orforglipron, offer comparable efficacy to injectables while potentially improving global accessibility by eliminating cold-chain requirements and simplifying manufacturing.”
Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators, perspectives and controversies. · Abstract
Identity
Orforglipron is a nonpeptide GLP-1 receptor agonist.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Data are needed regarding the efficacy and safety of the nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist orforglipron as a once-daily oral therapy for weight reduction in adults with obesity.”
Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. · Abstract
Identity
Orforglipron is a once-daily oral, non-peptide GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron is a novel once-daily oral non-peptide glucagon-like peptide-1 receptor agonist”
Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis. · BACKGROUND
Identity
Orforglipron (Foundayo™) is an oral, non-peptide GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron (Foundayo™) is an orally administered, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist”
Orforglipron: First Approval. · Abstract
Identity
Orforglipron is a novel oral small-molecule GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“This study assesses the efficacy and safety of the novel oral small molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) danuglipron and orforglipron”
The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis. · OBJECTIVE
Identity
Orforglipron is an oral, non-peptide GLP-1 receptor agonist.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“This study assessed the efficacy and safety of orforglipron, an oral, non-peptide GLP-1 receptor agonist, versus dapagliflozin, an oral SGLT2 inhibitor, in participants with type 2 diabetes and inadequate glycaemic control with metformin.”
Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial. · BACKGROUND
Identity
Orforglipron (LY3502970) is an oral, nonpeptide GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Oforglipron (LY3502970) is an oral, nonpeptide glucagon-like peptide-1 receptor (GLP-1R) agonist”
IUPHAR ligand commentary · General comments
Identity
Orforglipron (OFG) is an oral, non-peptide GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron (OFG), an oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1 RAs)”
Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta-Analysis of Randomised Clinical Trials. · BACKGROUND AND AIM
Identity
Orforglipron is an orally bioavailable, synthetic nonpeptide GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“One of the first molecules in the emerging class of GLP-1R NPAs is orforglipron”
The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. · Abstract
Identity
Orforglipron is a non-peptide, oral GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron is a non-peptide, oral glucagon-like peptide 1 receptor agonist”
Disposition and Absolute Bioavailability of Orally Administered Orforglipron in Healthy Participants. · Abstract
Identity
Orforglipron (OFG) is an oral, non-peptide GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron (OFG), an oral, non‐peptide glucagon‐like peptide‐1 receptor agonist (GLP‐1 RAs)”
Metabolic and Glycemic Effects of Orforglipron, a <scp>GLP</scp> ‐1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta‐Analysis of Randomised Clinical Trials · Abstract
Identity
Orforglipron is a once-daily oral GLP-1 receptor agonist.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron, a once daily oral glucagon-like-peptide-1 receptor agonist, may offer a more feasible and accepted therapeutic option.”
Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial. · INTRODUCTION
Identity
This article is a narrative review comparing where orforglipron fits among marketed GLP-1 receptor agonists using multiple types of evidence.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“This narrative review evaluates its comparative positioning among marketed GLP-1 receptor agonists by integrating structural, pharmacological, clinical, and practical evidence.”
Comparative Positioning of Orforglipron Among Selected GLP-1 Receptor Agonist Benchmarks: A Narrative Review. · Abstract
Identity
Orforglipron is a synthetic nonpeptide agonist of the GLP-1 receptor (GLP-1R).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“One of the first molecules in the emerging class of GLP-1R NPAs is orforglipron”
The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron · Abstract
Identity
Orforglipron is an oral small-molecule (non-peptide) GLP-1 receptor agonist.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“We aimed to evaluate orforglipron, an oral small-molecule (non-peptide) GLP-1 receptor agonist”
Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. · BACKGROUND
Identity
Orforglipron is an oral GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“oral glucagon-like peptide-1 receptor agonists (danuglipron vs orforglipron)”
Mechanistically resolved prediction of compound hepatotoxicity using primary human liver spheroids-Application to recent real-world cases. · Abstract
Identity
Orforglipron is an oral, non-peptide GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron, a novel small-molecule, non-peptide, oral glucagon-like peptide-1 receptor agonist (GLP-1 RA)”
Orforglipron for obesity treatment in older patients ≥65 years with or without type 2 diabetes: A post hoc subgroup analysis of the ATTAIN-1 and ATTAIN-2 trials. · BACKGROUND
Identity
Orforglipron (ORF) is an orally bioavailable, non-peptide GLP-1 receptor agonist that has completed Phase 3 clinical trials.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron (ORF), the first orally bioavailable non-peptide glucagon-like peptide-1 receptor (GLP-1R) agonist to complete Phase 3 clinical trials”
Variant-specific pharmacophoric shifts in glucagon-like peptide-1 receptor-orforglipron complexes revealed by Boltz-2 co-folding and membrane molecular dynamics. · BACKGROUND
Identity
Orforglipron is an oral, once-daily, non-peptide small-molecule GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron is a novel oral, once-daily, non-peptide small-molecule GLP-1 RA”
Potential nephroprotective mechanisms of orforglipron, an oral non-peptide GLP-1 receptor agonist. · Abstract
Identity
The review screened 245 records, removed 88 duplicates, assessed 157 unique records, and kept 35 sources focused on orforglipron.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“From 245 screened records, 88 duplicates were removed, 157 unique records were assessed, and 35 orforglipron-focused sources were retained.”
Comparative Positioning of Orforglipron Among Selected GLP-1 Receptor Agonist Benchmarks: A Narrative Review. · Abstract
Identity
Orforglipron’s molecular weight is 882.97.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Molecular weight: 882.97”
ORFORGLIPRON · Molecular properties
Identity
Orforglipron is included in the GLP-1 receptor agonist medication class.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“This medication class now includes oral formulations including oral semaglutide and the first non-peptide oral GLP-1RA, orforglipron”
Integrating glucagon-like peptide-1 receptor agonists into dermatology practice: Safety and monitoring strategies. · Abstract
Identity
Orforglipron’s molecular formula is C48H48F2N10O5.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Molecular formula: C48H48F2N10O5”
ORFORGLIPRON · Molecular properties
Identity
Orforglipron is a small-molecule, nonpeptide, oral GLP-1 receptor agonist.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron, a small-molecule, nonpeptide oral glucagon-like peptide-1 (GLP-1) receptor agonist”
Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. · Abstract
Identity
Orforglipron (LY3502970) is an oral, nonpeptide GLP-1 receptor agonist.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron (LY3502970) is a novel, orally available, nonpeptide glucagon-like peptide-1 receptor agonist (GLP-1 RA)”
Orforglipron: A Comprehensive Review of an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity and Type 2 Diabetes. · Abstract
Identity
Orforglipron is an oral small-molecule (non-peptide) GLP-1 receptor agonist.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“We aimed to evaluate orforglipron, an oral small-molecule (non-peptide) GLP-1 receptor agonist, for obesity treatment in adults with type 2 diabetes.”
Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. · BACKGROUND
Identity
Orforglipron is an oral, nonpeptide GLP-1 receptor agonist.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“The effects of orforglipron, an oral, nonpeptide glucagon-like peptide 1 receptor agonist, added to insulin glargine for treatment of type 2 diabetes have not been described.”
Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. · IMPORTANCE
Identity
Orforglipron is a small-molecule, nonpeptide, oral GLP-1 receptor agonist.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron, a small-molecule, nonpeptide oral glucagon-like peptide-1 (GLP-1) receptor agonist, is being investigated as a treatment for obesity.”
Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. · BACKGROUND
How does it work?
Target, response, and disposition.
Mechanism
Orforglipron binds the GLP-1 receptor at the upper helical bundle, not the usual orthosteric peptide site.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Unlike its predecessors, which bind an orthosteric peptide site, orforglipron binds the upper helical bundle of the same receptor.”
Potential nephroprotective mechanisms of orforglipron, an oral non-peptide GLP-1 receptor agonist. · Abstract
Mechanism
In binding tests, orforglipron bound human GLP-1R with high affinity (Ki = 1 nM) and was selective.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Competition binding experiments using either [125I]GLP-1(7-36)NH2or [3H]orforglipron indicated that orforglipron is a high-affinity [inhibition constant (Ki) = 1 nM], selective ligand of the human GLP-1R.”
The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. · Abstract
Mechanism
Orforglipron’s direct effects within the kidney are uncertain.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“The direct, intrarenal effects remain a point of uncertainty”
Potential nephroprotective mechanisms of orforglipron, an oral non-peptide GLP-1 receptor agonist. · Abstract
Mechanism
In binding experiments, orforglipron bound human GLP-1R with high affinity (Ki = 1 nM) and was selective.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Competition binding experiments using either [ 125 I]GLP-1(7-36)NH 2 or [ 3 H]orforglipron indicated that orforglipron is a high-affinity [inhibition constant ( K i ) = 1 nM], selective ligand of the human GLP-1R.”
The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron · Abstract
Mechanism
The authors say OFG dose–response on weight-related measures and glycemic outcomes has not been fully analyzed.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Its dose-response effects on body weight-related parameters and glycemic outcomes remain incompletely analysed.”
Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta-Analysis of Randomised Clinical Trials. · BACKGROUND AND AIM
Mechanism
They state that stronger binding alone doesn’t fully describe pharmacophoric quality.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Binding enhancement alone is insufficient to characterize pharmacophoric quality.”
Variant-specific pharmacophoric shifts in glucagon-like peptide-1 receptor-orforglipron complexes revealed by Boltz-2 co-folding and membrane molecular dynamics. · CONCLUSIONS
Mechanism
CHEMBL4446782 acts as a positive allosteric modulator at human GLP-1R in PSC-HEK293 cells (HTRF cAMP assay, 30 mins).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Assay: Positive allosteric modulator activity at human GLP-1R expressed in PSC-HEK293 cells in presence of EC20 level of GLP1(9-36)NH2 incubated for 30 mins by HTRF cAMP assay relative to control”
ChEMBL activities for CHEMBL4446782 · Activity 19054367
Mechanism
Orforglipron is a partial GLP-1R agonist that favors G protein signaling and does not recruit β-arrestin.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“It is a partial agonist (relative to native GLP-1), that biases GLP-1R signalling towards G protein activation and is devoid of β-arrestin recruitment activity.”
IUPHAR ligand commentary · General comments
Mechanism
In PSC-HEK293 cells expressing human GLP-1R, CHEMBL4446782 had EC50 600.0 nM as a positive allosteric modulator (30 min HTRF cAMP assay; EC20 GLP1(9-36)NH2).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
2 cited passages across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Standard result: EC50 = 600.0 nM”
ChEMBL activities for CHEMBL4446782 · Activity 19054382
- supports · Source-backed record
“Standard result: EC50 = 300.0 nM”
ChEMBL activities for CHEMBL4446782 · Activity 19054407
Mechanism
In signaling assays, orforglipron produced negligible β-arrestin recruitment.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“and negligible β-arrestin recruitment.”
The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. · Abstract
Mechanism
The drugs studied are oral small-molecule GLP-1 receptor agonists.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“We performed a meta-analysis of randomized controlled trials assessing the efficacy and safety of oral small-molecule GLP-1RAs in adults with T2D or obesity.”
Investigation into the efficacy and safety profile of oral small-molecule GLP-1 receptor agonists in type 2 diabetes and obesity: a systematic review and meta-analysis. · METHODS
Mechanism
CHEMBL4446782 was tested as a positive allosteric modulator at human GLP-1R by how it shifts GLP1(9-36)NH2 EC50 at 10 uM (30 mins, HTRF cAMP assay).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Assay: Positive allosteric modulator activity at human GLP-1R expressed in PSC-HEK293 cells assessed as potentiation of GLP1(9-36)NH2-induced cAMP accumulation by measuring shift in EC50 of endogenous GLP1(9-36)NH2 at 10 uM incubated for 30 mins by HTRF cAMP assay relative to control”
ChEMBL activities for CHEMBL4446782 · Activity 19054371
Mechanism
In signaling assays, orforglipron had low intrinsic efficacy and negligible β-arrestin recruitment.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Signal transduction assays showed that orforglipron has low intrinsic efficacy for effector activation and negligible β-arrestin recruitment.”
The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron · Abstract
Mechanism
Orforglipron is a G-protein-biased partial agonist that increases cyclic AMP, with little β-arrestin recruitment and less receptor internalization.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“It acts as a G-protein-biased partial agonist that stimulates cyclic AMP production, with minimal β-arrestin recruitment and decreased receptor internalization.”
Potential nephroprotective mechanisms of orforglipron, an oral non-peptide GLP-1 receptor agonist. · Abstract
Mechanism
Orforglipron is a G-protein-biased partial agonist that increases cyclic AMP, with minimal β-arrestin recruitment and less receptor internalization.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“It acts as a G-protein-biased partial agonist that stimulates cyclic AMP production, with minimal β-arrestin recruitment and decreased receptor internalization.”
Potential nephroprotective mechanisms of orforglipron, an oral non-peptide GLP-1 receptor agonist. · Abstract
Mechanism
They used random-effects models and reported OR, MD, and SMD with 95% CIs.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Random-effects models expressed OFG effects as odds ratios (OR), mean difference (MD) and standardised mean difference (SMD) with 95% confidence intervals (95% CI).”
Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta-Analysis of Randomised Clinical Trials. · METHODS
Mechanism
Orforglipron activates the GLP-1 receptor.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“oral glucagon-like peptide-1 receptor agonist (GLP-1 RA)”
Orforglipron for obesity treatment in older patients ≥65 years with or without type 2 diabetes: A post hoc subgroup analysis of the ATTAIN-1 and ATTAIN-2 trials. · BACKGROUND
Mechanism
In PSC-HEK293 cells expressing human GLP-1R, CHEMBL4446782 at 10 uM yielded a Ratio EC50 of 1681.0 in a 30 min HTRF cAMP potentiation assay (relative to control).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Standard result: Ratio EC50 = 1681.0”
ChEMBL activities for CHEMBL4446782 · Activity 19054371
Mechanism
Orforglipron was treated as an oral GLP-1 receptor agonist in this analysis.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Nine RCTs (N= 5766; 20-72 weeks) evaluating oral semaglutide, orforglipron, danuglipron, and lotiglipron were included.”
Role of Oral Glucagon-Like Peptide-1 Receptor Agonists in Weight Management for Individuals With Overweight or Obesity Without Diabetes: A Network Meta-Analysis of Randomized Controlled Trials. · RESULTS
Mechanism
Orforglipron binds the upper helical bundle of the GLP-1 receptor, not the usual orthosteric peptide site.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Unlike its predecessors, which bind an orthosteric peptide site, orforglipron binds the upper helical bundle of the same receptor.”
Potential nephroprotective mechanisms of orforglipron, an oral non-peptide GLP-1 receptor agonist. · Abstract
Mechanism
Orforglipron does not work at rodent receptors.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“and it is inactive at rodent receptors.”
Potential nephroprotective mechanisms of orforglipron, an oral non-peptide GLP-1 receptor agonist. · Abstract
Mechanism
In human-derived cell lines, orforglipron activated cAMP signaling.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Herein, we utilized human-derived neuronal and microglial cell lines to investigate these properties. Orforglipron activated cAMP signaling”
Orforglipron, a Small-Molecule Glucagon-like Peptide-1 Receptor Agonist (GLP-1RA), Has Neuroprotective and Anti-Inflammatory Effects. · Abstract
Mechanism
Orforglipron activates the GLP-1 receptor (it is a GLP-1 receptor agonist).
9 cited sources · 2 linked study IDs · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
12 cited passages across 9 source records. 5 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“glucagon-like peptide-1 (GLP-1) receptor agonist”
Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. · Abstract
- supports · Source-backed record
“Orforglipron, a once-daily oral nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist”
Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. · Abstract
- supports · Source-backed record
“Orforglipron (OFG), an oral, non‐peptide glucagon‐like peptide‐1 receptor agonist (GLP‐1 RAs)”
Metabolic and Glycemic Effects of Orforglipron, a <scp>GLP</scp> ‐1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta‐Analysis of Randomised Clinical Trials · Abstract
- supports · Source-backed record
“Embase, PubMed, Web of Science and Scopus were searched for randomised controlled trials.”
Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta-Analysis of Randomised Clinical Trials. · METHODS
- supports · Source-backed record
“Orforglipron (OFG), an oral, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1 RAs)”
Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta-Analysis of Randomised Clinical Trials. · BACKGROUND AND AIM
- supports · Source-backed record
“PRISMA guidelines were followed in our study.”
Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta-Analysis of Randomised Clinical Trials. · METHODS
- supports · Source-backed record
“orforglipron is a small-molecule biased GLP-1 receptor agonist”
Oral Incretin-Based Therapies for Weight Management. · RECENT FINDINGS
- supports · Source-backed record
“We employed an integrative computational framework that combines Boltz-2 deep learning co-folding for variant complex generation, 500 ns all-atom molecular dynamics simulations in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer, MM/GBSA binding free-energy decomposition, and protein ligand hydrogen-bond occupancy analysis.”
Variant-specific pharmacophoric shifts in glucagon-like peptide-1 receptor-orforglipron complexes revealed by Boltz-2 co-folding and membrane molecular dynamics. · METHODS
- supports · Source-backed record
“binds a distinct extracellular vestibule pocket not engaged by peptide GLP-1RAs.”
Variant-specific pharmacophoric shifts in glucagon-like peptide-1 receptor-orforglipron complexes revealed by Boltz-2 co-folding and membrane molecular dynamics. · BACKGROUND
- context · Source-backed record
“glucagon-like peptide 1 receptor agonists (GLP-1RAs) orforglipron and danuglipron”
Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: systematic review and meta-analysis of randomized controlled trials. · AIMS
- supports · Source-backed record
“Individual patient data from OASIS 4 and aggregate data from ATTAIN-1 informed anchored indirect treatment comparisons (ITCs).”
Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison. · MATERIALS AND METHODS
- supports · Source-backed record
“The synthesis was organized by comparative domains, including molecular structure, receptor pharmacology, early clinical pharmacology, direct comparative evidence, contextual comparator evidence, and practical administration.”
Comparative Positioning of Orforglipron Among Selected GLP-1 Receptor Agonist Benchmarks: A Narrative Review. · Abstract
Mechanism
In ATTAIN-OSA, people are randomized to placebo or an orforglipron capsule.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
2 cited passages across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Participants are randomly assigned to placebo or orforglipron capsule formulation”
Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial. · METHODS
- supports · Source-backed record
“Participants are randomly assigned to placebo or orforglipron capsule formulation at maximum tolerated dose (12, 24, or 36 mg) for 52 weeks following a standardized dose escalation schedule.”
Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial. · METHODS
Mechanism
The comparator, dapagliflozin, is described as an oral SGLT2 inhibitor.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“This study assessed the efficacy and safety of orforglipron, an oral, non-peptide GLP-1 receptor agonist, versus dapagliflozin, an oral SGLT2 inhibitor, in participants with type 2 diabetes and inadequate glycaemic control with metformin.”
Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial. · BACKGROUND
Mechanism
In signaling assays, orforglipron had low intrinsic efficacy for activating effectors.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Signal transduction assays showed that orforglipron has low intrinsic efficacy for effector activation”
The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. · Abstract
Mechanism
In PSC-HEK293 cells expressing human GLP-1R, CHEMBL4446782 acted as a positive allosteric modulator with Emax 91.0% (30 min HTRF cAMP assay; EC20 GLP1(9-36)NH2; relative to control).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
2 cited passages across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Standard result: Emax = 100.0 %”
ChEMBL activities for CHEMBL4446782 · Activity 19054408
- supports · Source-backed record
“Standard result: Emax = 91.0 %”
ChEMBL activities for CHEMBL4446782 · Activity 19054367
Pharmacokinetics
After a single 0.3 to 6 mg dose, the mean half-life was 24.6 to 35.3 hours.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“the mean t 1/2 was 24.6 to 35.3 hours after a single dose (0.3‐6 mg).”
Orforglipron ( <scp>LY3502970</scp> ), a novel, oral non‐peptide glucagon‐like peptide‐1 receptor agonist: A Phase 1a, blinded, placebo‐controlled, randomized, single‐ and multiple‐ascending‐dose study in healthy participants · Abstract
Pharmacokinetics
Two phase 1 open-label studies tested how orforglipron is handled by the body and its absolute bioavailability in healthy adults.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Two phase 1, open-label studies evaluated the disposition and absolute bioavailability of orforglipron in healthy adults.”
Disposition and Absolute Bioavailability of Orally Administered Orforglipron in Healthy Participants. · Abstract
Pharmacokinetics
Most [14C]-orforglipron-related radioactivity was eliminated in feces (87% ± 2.8%), with little in urine (0.2% ± 0.02%).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“The primary route of elimination for [14C]-orforglipron-related radioactivity was via the feces (87% ± 2.8%) with minimal urinary excretion (0.2% ± 0.02%).”
Disposition and Absolute Bioavailability of Orally Administered Orforglipron in Healthy Participants. · Abstract
Pharmacokinetics
On Day 28 (2 to 24 mg), the mean half-life was 48.1 to 67.5 hours.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“On Day 28, the mean t 1/2 was 48.1 to 67.5 hours across the dose range (2‐24 mg).”
Orforglipron ( <scp>LY3502970</scp> ), a novel, oral non‐peptide glucagon‐like peptide‐1 receptor agonist: A Phase 1a, blinded, placebo‐controlled, randomized, single‐ and multiple‐ascending‐dose study in healthy participants · Abstract
Pharmacokinetics
In study B, orforglipron was extensively oxidized and then its oxadiazolone ring underwent microbial metabolism.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Metabolite profiling from study B showed that orforglipron underwent extensive oxidative metabolism, followed by microbial metabolism of the oxadiazolone ring.”
Disposition and Absolute Bioavailability of Orally Administered Orforglipron in Healthy Participants. · Abstract
Pharmacokinetics
Orforglipron is metabolized almost entirely by the liver.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
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- supports · Source-backed record
“Its metabolism is almost entirely hepatic”
Potential nephroprotective mechanisms of orforglipron, an oral non-peptide GLP-1 receptor agonist. · Abstract
What has been studied?
What the evidence says.
Comparative evidence
With 12 mg, the estimated treatment difference vs placebo at week 72 was -4·5 (95% CI -5·5 to -3·6); p<0·0001.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“ETD -4·5 [-5·5 to -3·6]; p<0·0001”
Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. · FINDINGS
Comparative evidence
With 6 mg, the estimated treatment difference vs placebo at week 72 was -2·7 (95% CI -3·7 to -1·6); p<0·0001.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
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- supports · Source-backed record
“estimated treatment difference [ETD] -2·7 [95% CI -3·7 to -1·6]; p<0·0001”
Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. · FINDINGS
Comparative evidence
For HbA1c at week 40, each orforglipron dose was superior to placebo: treatment differences were -0.78% (3 mg), -1.08% (12 mg), and -1.03% (36 mg), with P < .001 for all.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
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- supports · Source-backed record
“Each dosage of orforglipron was superior to placebo (estimated treatment differences: 3 mg once daily, -0.78% [95% CI, -1.02% to -0.55%]; 12 mg once daily, -1.08% [95% CI, -1.33% to -0.83%]; 36 mg once daily, -1.03% [95% CI, -1.28% to -0.77%]; P < .001 for all).”
Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. · RESULTS
Comparative evidence
Comparators included placebo, oral semaglutide, dapagliflozin, and insulin glargine.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
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- supports · Source-backed record
“pooled comparator [placebo, oral semaglutide, dapagliflozin, insulin glargine]”
Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials. · MATERIALS AND METHODS
Comparative evidence
The conclusion states orforglipron and high-dose oral semaglutide had the most consistent, substantial weight reductions, but comparisons are limited by low-to-moderate certainty and no head-to-head trials.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“HiD oral semaglutide and orforglipron demonstrated the most consistent and substantial weight reductions though low-to-moderate certainty and lack of head-to-head comparisons constrain comparative inference.”
Role of Oral Glucagon-Like Peptide-1 Receptor Agonists in Weight Management for Individuals With Overweight or Obesity Without Diabetes: A Network Meta-Analysis of Randomized Controlled Trials. · CONCLUSION
Comparative evidence
In diet-induced obese Glp1rS33W rats, oral orforglipron was associated with weight loss versus subcutaneous semaglutide.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Diet-induced obesity inGlp1rS33Wrats enabled studies showing weight loss in animals orally administered orforglipron versus subcutaneous injection of GLP-1R agonist semaglutide.”
The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. · Abstract
Comparative evidence
With 36 mg, the estimated treatment difference vs placebo at week 72 was -7·1 (95% CI -8·2 to -6·1); p<0·0001.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“ETD -7·1 [-8·2 to -6·1]; p<0·0001”
Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. · FINDINGS
Comparative evidence
The trials compared oral GLP-1 receptor agonists with placebo in adults without diabetes.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
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- supports · Source-backed record
“A frequentist random-effects NMA of RCTs comparing oral GLP-1 RAs with placebo in adults without diabetes was conducted by searching databases through 30 April 2026.”
Role of Oral Glucagon-Like Peptide-1 Receptor Agonists in Weight Management for Individuals With Overweight or Obesity Without Diabetes: A Network Meta-Analysis of Randomized Controlled Trials. · METHODS
Comparative evidence
Limitations included no comparator arm with continued injectable obesity medicines and a 1-year duration.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Trial limitations include the absence of a comparator arm involving continued use of injectable obesity-management medications and the trial's 1-year duration.”
Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. · Abstract
Study findings
By week 26, average weight change was -8.6% to -12.6% with orforglipron and -2.0% with placebo.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“At week 26, the mean change from baseline in body weight ranged from -8.6% to -12.6% across the orforglipron dose cohorts and was -2.0% in the placebo group.”
Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. · Abstract
Study findings
In cohort 1, maintained weight reduction at week 52 was 74.7% with orforglipron vs 49.2% with placebo (difference 25.5%; 95% CI 14.5 to 36.5; P < 0.001).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
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“Cohort 1 participants who achieved body weight plateau maintained a model-based estimate (MBE) of 74.7% (s.e.m. 4.05) of body weight reduction with orforglipron compared with an MBE of 49.2% (s.e.m. 3.92) with placebo, resulting in an estimated treatment difference of MBE 25.5% (95% confidence interval 14.5 to 36.5); P < 0.001; treatment-regimen estimand) at week 52.”
Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. · Abstract
Study findings
In meta-analysis, orforglipron lowered fasting plasma glucose (MD: -26.91; 95% CI: -31.05, -22.78).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“FPG (MD: -26.91; 95% CI: -31.05, -22.78)”
The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis. · RESULTS
Study findings
With follow-up up to 36 weeks, 36 mg/day orforglipron reduced percent body weight more than placebo (MD -8.84%).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“36 mg/day (MD -8.84%, 95% CI [-11.68, -6.00],p< 0.01)”
Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis. · RESULTS
Study findings
The analysis included six RCTs with 4878 participants.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Six RCTs comprising 4878 participants were included.”
Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta-Analysis of Randomised Clinical Trials. · RESULTS
Study findings
At week 72, mean bodyweight change was -5·1% with orforglipron 6 mg and -2·5% with placebo (treatment regimen estimand).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“For the treatment regimen estimand, the mean percent change in bodyweight from baseline to week 72 was -5·1% (95% CI -6·0 to -4·2) with 6 mg”
Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. · FINDINGS
Study findings
Oral small-molecule GLP-1RAs reduced body weight (MD=-3.93, 95% CI -4.78 to -3.09).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
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- supports · Source-backed record
“Oral small-molecule GLP-1RAs significantly reduced body weight (MD=-3.93, 95%CI:-4.78 to -3.09)”
Investigation into the efficacy and safety profile of oral small-molecule GLP-1 receptor agonists in type 2 diabetes and obesity: a systematic review and meta-analysis. · RESULTS
Study findings
In adults aged 65 years or older with obesity (with or without type 2 diabetes), orforglipron led to greater weight loss than placebo at Week 72.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“In this post hoc analysis of adults ≥65 years of age with obesity with or without type 2 diabetes, once-daily orforglipron was associated with significantly greater reductions in body weight vs. placebo at Week 72.”
Orforglipron for obesity treatment in older patients ≥65 years with or without type 2 diabetes: A post hoc subgroup analysis of the ATTAIN-1 and ATTAIN-2 trials. · CONCLUSION
Study findings
By week 40, HbA1c fell by -1.88% with orforglipron 12 mg once daily vs -0.79% with placebo.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“At week 40, the mean changes from baseline in HbA1c were -1.58%, -1.88%, and -1.82% with orforglipron, 3 mg, 12 mg, and 36 mg once daily, respectively, vs -0.79% with placebo.”
Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. · RESULTS
Study findings
By week 36, average weight change was -9.4% to -14.7% with orforglipron and -2.3% with placebo.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“At week 36, the mean change ranged from -9.4% to -14.7% with orforglipron and was -2.3% with placebo.”
Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. · Abstract
Study findings
At week 40, HbA1c fell by -1·56% with orforglipron 36 mg vs -0·81% with dapagliflozin; the difference was -0·75% (95% CI -0·96 to -0·55; p<0·0001).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
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“Change from baseline in mean HbA1cwas -1·23% (SE 0·08), -1·50% (0·08), and -1·56% (0·09) with orforglipron 3 mg, 12 mg, and 36 mg, respectively, versus -0·81% (0·07) with dapagliflozin 10 mg; estimated treatment difference versus dapagliflozin was -0·42% (95% CI -0·62 to -0·23), -0·70% (-0·90 to -0·49), and -0·75% (-0·96 to -0·55) with orforglipron 3 mg, 12 mg, and 36 mg, respectively (all p<0·0001).”
Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial. · FINDINGS
Study findings
Orforglipron was associated with mean reductions in ALT and AST.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron treatment was associated with mean reductions in ALT/AST.”
Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials. · RESULTS
Study findings
With follow-up up to 36 weeks, 45 mg/day orforglipron reduced percent body weight more than placebo (MD -8.24%).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“45 mg/day (MD -8.24%, 95% CI [-12.84, -3.63],p< 0.01)”
Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis. · RESULTS
Study findings
Over 72 weeks in adults with obesity, orforglipron reduced body weight significantly more than placebo.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“In adults with obesity, 72-week treatment with orforglipron led to significantly greater reductions in body weight than placebo”
Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. · Abstract
Study findings
More people achieved >15% weight loss with 24 mg/day orforglipron than with placebo (OR 21.90).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“The percentage of patients being able to achieve >15% weight loss from baseline was significantly higher with orforglipron 24 mg/day [Odds ratio (OR) 21.90 (95% CI [4.06, 118.15],p= 0.0003)”
Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis. · RESULTS
Study findings
Orforglipron lowered fasting glucose from Days 1 to 28.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron decreased fasting glucose levels across Days 1 to 28”
Orforglipron ( <scp>LY3502970</scp> ), a novel, oral non‐peptide glucagon‐like peptide‐1 receptor agonist: A Phase 1a, blinded, placebo‐controlled, randomized, single‐ and multiple‐ascending‐dose study in healthy participants · Abstract
Study findings
CHEMBL4446782 had an EC50 of 600.0 nM at human GLP-1R in a PSC-HEK293 HTRF cAMP assay (30 mins, with EC20 GLP1(9-36)NH2).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
2 cited passages across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Standard result: EC50 = 300.0 nM”
ChEMBL activities for CHEMBL4446782 · Activity 19054407
- supports · Source-backed record
“Standard result: EC50 = 600.0 nM”
ChEMBL activities for CHEMBL4446782 · Activity 19054382
Study findings
In a meta-analysis, once-daily oral orforglipron reduced body weight in a dose-dependent way in obese adults with and without diabetes.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron produced consistent, dose-dependent reductions in body weight”
Efficacy and Safety of Oral GLP-1 RA Orforglipron on Weight and Glycemic Control According to Diabetes Status: A Systematic Review and Meta-Analysis. · Abstract
Study findings
High-dose orforglipron had an estimated absolute weight loss of -12.2 kg versus placebo in this network meta-analysis.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron HiD produced the greatest absolute weight loss (MD -12.2 kg), whereas semaglutide HiD reduced BMI (MD -4.7 kg/m2) and waist circumference (MD -10.0 cm) the most.”
Role of Oral Glucagon-Like Peptide-1 Receptor Agonists in Weight Management for Individuals With Overweight or Obesity Without Diabetes: A Network Meta-Analysis of Randomized Controlled Trials. · RESULTS
Study findings
OFG reduced body weight, BMI, and waist circumference across all follow-ups.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“OFG demonstrated reductions in body weight, BMI and waist circumference across all follow-ups.”
Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta-Analysis of Randomised Clinical Trials. · RESULTS
Study findings
The analysis pooled six RCTs with 4878 participants.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Six RCTs comprising 4878 participants were included.”
Metabolic and Glycemic Effects of Orforglipron, a <scp>GLP</scp> ‐1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta‐Analysis of Randomised Clinical Trials · Abstract
Study findings
All orforglipron doses beat placebo on HbA1c at week 40 (treatment differences: -0.78%, -1.08%, and -1.03%; P < .001 for all).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Each dosage of orforglipron was superior to placebo (estimated treatment differences: 3 mg once daily, -0.78% [95% CI, -1.02% to -0.55%]; 12 mg once daily, -1.08% [95% CI, -1.33% to -0.83%]; 36 mg once daily, -1.03% [95% CI, -1.28% to -0.77%]; P < .001 for all).”
Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. · RESULTS
Study findings
In a human microglial cell line, orforglipron reduced LPS- and glutamate-induced secretion of IL-6, IL-8, and MCP-1.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Additionally, orforglipron effectively mitigated LPS- and glutamate-induced proinflammatory protein secretion (IL-6, IL-8, and MCP-1) from a human microglial cell line.”
Orforglipron, a Small-Molecule Glucagon-like Peptide-1 Receptor Agonist (GLP-1RA), Has Neuroprotective and Anti-Inflammatory Effects. · Abstract
Study findings
ATTAIN-OSA randomized 712 participants (Study 1: 363; Study 2: 349) to orforglipron or placebo.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Overall, 712 participants have been randomized to orforglipron or placebo (Study 1, n = 363; Study 2, n = 349).”
Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial. · RESULTS
Study findings
ATTAIN-OSA was created to test oral orforglipron’s efficacy and safety in adults with moderate-to-severe OSA.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“ATTAIN-OSA was developed to evaluate the efficacy and safety of oral orforglipron in adults with moderate-to-severe OSA.”
Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial. · INTRODUCTION
Study findings
By week 40, all tested orforglipron doses were non-inferior to dapagliflozin for lowering HbA1c.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“At week 40, for the treatment regimen estimand, all orforglipron doses were non-inferior to dapagliflozin in reducing HbA1c.”
Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial. · FINDINGS
Study findings
At week 40, HbA1c fell by -1·23% with orforglipron 3 mg vs -0·81% with dapagliflozin; the difference was -0·42% (95% CI -0·62 to -0·23; p<0·0001).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Change from baseline in mean HbA1cwas -1·23% (SE 0·08), -1·50% (0·08), and -1·56% (0·09) with orforglipron 3 mg, 12 mg, and 36 mg, respectively, versus -0·81% (0·07) with dapagliflozin 10 mg; estimated treatment difference versus dapagliflozin was -0·42% (95% CI -0·62 to -0·23), -0·70% (-0·90 to -0·49), and -0·75% (-0·96 to -0·55) with orforglipron 3 mg, 12 mg, and 36 mg, respectively (all p<0·0001).”
Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial. · FINDINGS
Study findings
In meta-analysis, orforglipron reduced weight (MD: -6.28; 95% CI: -8.45, -4.11).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“weight (MD: -6.28; 95% CI: -8.45, -4.11)”
The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis. · RESULTS
Study findings
At week 72, mean bodyweight change was -9·6% with orforglipron 36 mg (treatment regimen estimand).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“-9·6% (-10·5 to -8·7) with 36 mg orforglipron”
Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. · FINDINGS
Study findings
In ATTAIN-1 participants aged 65 years or older, orforglipron reduced body weight more than placebo at Week 72.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“At Week 72, the percent change in weight from baseline among participants from ATTAIN-1 was -7.9% (95% CI: -10.0, -5.9), -11.3% (-13.4, -9.3), and -13.0% (-15.7, -10.4) with orforglipron 5.5 mg, 9 mg, and 17.2 mg, respectively, vs. -1.6% (-3.2, 0.1) with placebo (all p < 0.001)”
Orforglipron for obesity treatment in older patients ≥65 years with or without type 2 diabetes: A post hoc subgroup analysis of the ATTAIN-1 and ATTAIN-2 trials. · RESULTS
Study findings
More people achieved >15% weight loss with 45 mg/day orforglipron than with placebo (OR 23.17).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“45 mg/day (OR 23.17, 95% CI [4.37, 123.03],p= 0.0002)”
Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis. · RESULTS
Study findings
By week 36, 46 to 75% on orforglipron achieved at least 10% weight loss vs 9% on placebo.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“A weight reduction of at least 10% by week 36 occurred in 46 to 75% of the participants who received orforglipron, as compared with 9% who received placebo.”
Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. · Abstract
Study findings
By week 40, HbA1c fell by -1.82% with orforglipron 36 mg once daily vs -0.79% with placebo.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“At week 40, the mean changes from baseline in HbA1c were -1.58%, -1.88%, and -1.82% with orforglipron, 3 mg, 12 mg, and 36 mg once daily, respectively, vs -0.79% with placebo.”
Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. · RESULTS
Study findings
In mice with human GLP-1R, low receptor occupancy by orforglipron was enough to produce a full biological response.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“These experiments revealed that low GLP-1R occupancy by orforglipron is sufficient to yield a full biological response.”
The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. · Abstract
Study findings
More people achieved >15% weight loss with 36 mg/day orforglipron than with placebo (OR 17.43).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“36 mg/day (OR 17.43, 95% CI [3.18, 95.66],p= 0.001)”
Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis. · RESULTS
Study findings
CHEMBL4446782 reached an Emax of 91.0 % (relative to control) in a human GLP-1R HTRF cAMP assay (30 mins).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
2 cited passages across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Standard result: Emax = 100.0 %”
ChEMBL activities for CHEMBL4446782 · Activity 19054408
- supports · Source-backed record
“Standard result: Emax = 91.0 %”
ChEMBL activities for CHEMBL4446782 · Activity 19054367
Study findings
By week 40, HbA1c fell by -1.58% with orforglipron 3 mg once daily vs -0.79% with placebo.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“At week 40, the mean changes from baseline in HbA1c were -1.58%, -1.88%, and -1.82% with orforglipron, 3 mg, 12 mg, and 36 mg once daily, respectively, vs -0.79% with placebo.”
Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. · RESULTS
Study findings
Across six RCTs, orforglipron lowered body weight, BMI, and waist circumference at the follow-up times studied.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“OFG demonstrated reductions in body weight, BMI and waist circumference across all follow‐ups.”
Metabolic and Glycemic Effects of Orforglipron, a <scp>GLP</scp> ‐1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta‐Analysis of Randomised Clinical Trials · Abstract
Study findings
At week 40, HbA1c fell by -1·50% with orforglipron 12 mg vs -0·81% with dapagliflozin; the difference was -0·70% (95% CI -0·90 to -0·49; p<0·0001).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Change from baseline in mean HbA1cwas -1·23% (SE 0·08), -1·50% (0·08), and -1·56% (0·09) with orforglipron 3 mg, 12 mg, and 36 mg, respectively, versus -0·81% (0·07) with dapagliflozin 10 mg; estimated treatment difference versus dapagliflozin was -0·42% (95% CI -0·62 to -0·23), -0·70% (-0·90 to -0·49), and -0·75% (-0·96 to -0·55) with orforglipron 3 mg, 12 mg, and 36 mg, respectively (all p<0·0001).”
Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial. · FINDINGS
Study findings
ATTAIN-OSA was developed to test the efficacy and safety of oral orforglipron in adults with moderate-to-severe OSA.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“ATTAIN-OSA was developed to evaluate the efficacy and safety of oral orforglipron in adults with moderate-to-severe OSA.”
Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial. · INTRODUCTION
Study findings
In human-derived neuronal cells, orforglipron protected cells from excitotoxic glutamate and oxidative stress.
1 cited source · Study independence not established
Animal or laboratory findings do not establish benefit or safety in people.
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron activated cAMP signaling and shielded neuronal cells from excitotoxic glutamate and oxidative stress, which are common in neurodegenerative diseases and injuries.”
Orforglipron, a Small-Molecule Glucagon-like Peptide-1 Receptor Agonist (GLP-1RA), Has Neuroprotective and Anti-Inflammatory Effects. · Abstract
Study findings
In meta-analysis, orforglipron lowered HbA1c (MD: -1.02; 95% CI: -1.18, -0.86).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Orforglipron also showed significant positive effects on HbA1c (MD: -1.02; 95% CI: -1.18, -0.86)”
The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis. · RESULTS
Study findings
In meta-analysis, orforglipron reduced BMI (MD: -2.64; 95% CI: -3.38, -1.89).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“BMI (MD: -2.64; 95% CI: -3.38, -1.89)”
The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis. · RESULTS
Study findings
With follow-up up to 36 weeks, 24 mg/day orforglipron reduced percent body weight more than placebo (MD -8.51%).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“24 mg/day (MD -8.51%, 95% confidence interval (CI) [-9.88, -7.14],p< 0.01)”
Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis. · RESULTS
Study findings
In ATTAIN-2 participants aged 65 years or older, orforglipron reduced body weight more than placebo at Week 72.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“which was similar for those in ATTAIN-2 (orforglipron 5.5 mg: -7.5% [-9.1, -5.9]; 9 mg: -8.3% [-9.7, -6.8]; 17.2 mg: -12.2% [-13.9, -10.6]; placebo: -2.3% [-3.1, -1.4]; all p < 0.001)”
Orforglipron for obesity treatment in older patients ≥65 years with or without type 2 diabetes: A post hoc subgroup analysis of the ATTAIN-1 and ATTAIN-2 trials. · RESULTS
Study findings
At week 72, mean bodyweight change was -7·0% with orforglipron 12 mg (treatment regimen estimand).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“-7·0% (-7·8 to -6·2) with 12 mg”
Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. · FINDINGS
Study findings
In this network meta-analysis of RCTs in adults without diabetes, orforglipron reduced percent body weight more than placebo (MD -11.8%).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“All agents except low-dose (LoD) lotiglipron outperformed placebo in percent body weight reduction; high-dose (HiD) semaglutide (MD -11.6%) and orforglipron (MD -11.8%) showed the greatest effects.”
Role of Oral Glucagon-Like Peptide-1 Receptor Agonists in Weight Management for Individuals With Overweight or Obesity Without Diabetes: A Network Meta-Analysis of Randomized Controlled Trials. · RESULTS
Study findings
Gastric emptying was delayed on Day 28.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“gastric emptying was delayed on Day 28.”
Orforglipron ( <scp>LY3502970</scp> ), a novel, oral non‐peptide glucagon‐like peptide‐1 receptor agonist: A Phase 1a, blinded, placebo‐controlled, randomized, single‐ and multiple‐ascending‐dose study in healthy participants · Abstract
Study findings
By week 40, HbA1c fell by -1.58%, -1.88%, and -1.82% with orforglipron 3 mg, 12 mg, and 36 mg once daily, versus -0.79% with placebo.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“At week 40, the mean changes from baseline in HbA1c were -1.58%, -1.88%, and -1.82% with orforglipron, 3 mg, 12 mg, and 36 mg once daily, respectively, vs -0.79% with placebo.”
Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. · RESULTS
Study findings
Key secondary endpoints include hypoxic burden, PROMIS sleep-related impairment, hs-CRP, and body weight.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Key secondary endpoints include sleep apnea-specific hypoxic burden, Patient-Reported Outcomes Measurement Information System sleep-related impairment, high-sensitivity C-reactive protein, and body weight”
Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial. · RESULTS
Study findings
In adults with obesity without diabetes, taking orforglipron once daily for 72 weeks reduced body weight more than placebo.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“The mean change in body weight from baseline to week 72 was -7.5% (95% confidence interval [CI], -8.2 to -6.8) with 6 mg of orforglipron, -8.4% (95% CI, -9.1 to -7.7) with 12 mg of orforglipron, and -11.2% (95% CI, -12.0 to -10.4) with 36 mg of orforglipron, as compared with -2.1% (95% CI, -2.8 to -1.4) with placebo (P < 0.001 for all comparisons with placebo).”
Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. · Abstract
Study findings
Daily oral orforglipron was associated with weight loss.
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Daily oral orforglipron, a nonpeptide GLP-1 receptor agonist, was associated with weight reduction.”
Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. · Abstract
Study findings
With follow-up up to 36 weeks, 12 mg/day orforglipron reduced percent body weight more than placebo (MD -5.48%).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Evidence boundary: Applies only to the source-defined population, formulation, dose, and assessment period.
Exact passages, locators, and provenance
- supports · Source-backed record
“Compared to placebo, patients receiving orforglipron 12 mg/day (mean difference (MD), MD -5.48%, 95% CI [-7.64, -3.33],p< 0.01)”
Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis. · RESULTS
Risks and interactions
Risks, organized for scanning.
This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.
Products and regulatory status
Same ingredient. Different records.
This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.
Administration context
The practical clinical context.
This profile does not yet contain a published summary for this topic. This is a coverage gap, not evidence that no research exists.
Additional research & classification gaps
23 archived statements are kept separate from drug-effect findings. Media studies, economic models, methods, and records with unresolved scope are not used as medical-effect evidence.
Inspect contextual research (23)
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
2 cited passages across 1 source record. 1 publication group(s) lack a resolved study identity.
Oral semaglutide 25 mg reduced body weight more than orforglipron 36 mg (mean difference -3.0%-points; 95% CI -5.8, -0.3; efficacy estimand).
Research context only—not evidence of a treatment effect.
- Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison.
Population-adjusted analyses showed a significantly greater percentage change from baseline in body weight with oral semaglutide 25 mg than with orforglipron 36 mg, with mean differences (MDs) of -3.2%-points (95% confidence intervals [CIs]: -5.9, -0.4; treatment-regimen estimand)
- Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison.
and -3.0%-points (95% CI: -5.8, -0.3; efficacy estimand).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The review also selected seven comparator trials to benchmark oral semaglutide (in type 2 diabetes and obesity), danuglipron, and injectable semaglutide.
Research context only—not evidence of a treatment effect.
- Comparative Positioning of Orforglipron Among Selected GLP-1 Receptor Agonist Benchmarks: A Narrative Review.
Seven additional comparator trials were selected through targeted citation verification because they represented clinically relevant benchmarks for oral semaglutide in type 2 diabetes and obesity, danuglipron as another oral small-molecule GLP-1 receptor agonist, and injectable semaglutide as a high-efficacy class comparator.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
The review says orforglipron has emerging comparative evidence and should not be seen as a broadly superior replacement for existing agents.
Research context only—not evidence of a treatment effect.
- Comparative Positioning of Orforglipron Among Selected GLP-1 Receptor Agonist Benchmarks: A Narrative Review.
At present, orforglipron should be viewed as an oral small-molecule GLP-1 receptor agonist with emerging comparative evidence, rather than as a broadly superior replacement for existing agents.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Indirect comparisons are limited because studies differ in populations, doses, follow-up duration, comparators, and endpoints.
Research context only—not evidence of a treatment effect.
- Comparative Positioning of Orforglipron Among Selected GLP-1 Receptor Agonist Benchmarks: A Narrative Review.
However, indirect comparisons remain limited by differences in populations, doses, follow-up duration, comparators, and endpoints.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
There is direct comparator evidence for orforglipron versus dulaglutide and versus oral semaglutide.
Research context only—not evidence of a treatment effect.
- Comparative Positioning of Orforglipron Among Selected GLP-1 Receptor Agonist Benchmarks: A Narrative Review.
Current evidence identifies several domains relevant to the comparative positioning of orforglipron, including its nonpeptide small-molecule structure, receptor pharmacology, once-daily oral dosing profile, and direct comparator evidence against dulaglutide and oral semaglutide.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Oral small-molecule GLP-1RAs increased the chance of achieving at least 5%, 10%, or 15% weight loss (RRs 2.68, 4.14, and 10.61, respectively).
Research context only—not evidence of a treatment effect.
- Investigation into the efficacy and safety profile of oral small-molecule GLP-1 receptor agonists in type 2 diabetes and obesity: a systematic review and meta-analysis.
These agents increased likelihood of achieving weight loss, including ≥5% (RR = 2.68, 95% CI: 2.24 to 3.20), ≥10% (RR = 4.14, 95% CI: 3.19 to 5.36), and ≥15% body weight reduction (RR = 10.61, 95% CI: 7.76 to 14.49).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
CHEMBL4446782 had an EC50 of 1.2 nM in the hGLP1R-HEK293 cAMP assay entry.
Research context only—not evidence of a treatment effect.
- ChEMBL activities for CHEMBL4446782
Standard result: EC50 = 1.2 nM
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
The main outcome was percent change in body weight from baseline to week 72 (intention-to-treat, treatment-regimen estimand).
Research context only—not evidence of a treatment effect.
- Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment.
The primary end point was the percent change in body weight from baseline to week 72, as assessed according to the treatment-regimen estimand in the intention-to-treat population.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
In animal models, oral LY3502970 lowers glucose comparably to injectable exenatide.
Research context only—not evidence of a treatment effect.
- IUPHAR ligand commentary
Orally administered LY3502970 has glucose lowering effects in animal models that are comparable to the effects of injectable peptide agonist exenatide
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Mean body-weight change at week 72 was -11.2% with 36 mg orforglipron vs -2.1% with placebo.
Research context only—not evidence of a treatment effect.
- Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment.
The mean change in body weight from baseline to week 72 was -7.5% (95% confidence interval [CI], -8.2 to -6.8) with 6 mg of orforglipron, -8.4% (95% CI, -9.1 to -7.7) with 12 mg of orforglipron, and -11.2% (95% CI, -12.0 to -10.4) with 36 mg of orforglipron, as compared with -2.1% (95% CI, -2.8 to -1.4) with placebo (P<0.001 for all comparisons with placebo).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
It is not known if orforglipron’s metabolic similarity to semaglutide leads to similar kidney protection.
Research context only—not evidence of a treatment effect.
- Potential nephroprotective mechanisms of orforglipron, an oral non-peptide GLP-1 receptor agonist.
It is unknown whether this metabolic similarity manifests with comparable nephroprotection
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Mean body-weight change at week 72 was -8.4% with 12 mg orforglipron vs -2.1% with placebo.
Research context only—not evidence of a treatment effect.
- Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment.
The mean change in body weight from baseline to week 72 was -7.5% (95% confidence interval [CI], -8.2 to -6.8) with 6 mg of orforglipron, -8.4% (95% CI, -9.1 to -7.7) with 12 mg of orforglipron, and -11.2% (95% CI, -12.0 to -10.4) with 36 mg of orforglipron, as compared with -2.1% (95% CI, -2.8 to -1.4) with placebo (P<0.001 for all comparisons with placebo).
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Orforglipron is being studied as a treatment for obesity.
Research context only—not evidence of a treatment effect.
- Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment.
Orforglipron, a small-molecule, nonpeptide oral glucagon-like peptide-1 (GLP-1) receptor agonist, is being investigated as a treatment for obesity.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Orforglipron (as an oral GLP-1 agonist) may improve global access because it could avoid cold-chain needs and simplify manufacturing.
Research context only—not evidence of a treatment effect.
- Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators, perspectives and controversies.
Oral GLP-1 agonists, including orforglipron, offer comparable efficacy to injectables while potentially improving global accessibility by eliminating cold-chain requirements and simplifying manufacturing.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Oral small-molecule GLP-1RAs lowered fasting blood glucose (MD=-24.59, 95% CI -28.80 to -20.37) and HbA1c (MD=-0.94, 95% CI -1.09 to -0.79).
Research context only—not evidence of a treatment effect.
- Investigation into the efficacy and safety profile of oral small-molecule GLP-1 receptor agonists in type 2 diabetes and obesity: a systematic review and meta-analysis.
Oral small-molecule GLP-1RAs significantly reduced body weight (MD=-3.93, 95%CI:-4.78 to -3.09), body mass index (MD=-2.39, 95%CI:-3.02 to -1.77), waist circumference (MD=-4.62, 95%CI:-6.09 to -3.16), fasting blood glucose (MD=-24.59, 95%CI:-28.80 to -20.37), and HbA1c (MD=-0.94, 95%CI: -1.09 to -0.79), while fasting insulin was not significantly changed (MD = 1.21, 95%CI: -0.77 to 3.19).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
CHEMBL4446782 had an EC50 of 1.2 nM in the HEK293 HTRF assay entry for agonist activity.
Research context only—not evidence of a treatment effect.
- ChEMBL activities for CHEMBL4446782
Standard result: EC50 = 1.2 nM
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Orforglipron (as an oral GLP-1 agonist) is said to have efficacy comparable to injectable options.
Research context only—not evidence of a treatment effect.
- Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators, perspectives and controversies.
Oral GLP-1 agonists, including orforglipron, offer comparable efficacy to injectables while potentially improving global accessibility by eliminating cold-chain requirements and simplifying manufacturing.
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Oral small-molecule GLP-1RAs did not significantly change fasting insulin (MD=1.21, 95% CI -0.77 to 3.19).
Research context only—not evidence of a treatment effect.
- Investigation into the efficacy and safety profile of oral small-molecule GLP-1 receptor agonists in type 2 diabetes and obesity: a systematic review and meta-analysis.
Oral small-molecule GLP-1RAs significantly reduced body weight (MD=-3.93, 95%CI:-4.78 to -3.09), body mass index (MD=-2.39, 95%CI:-3.02 to -1.77), waist circumference (MD=-4.62, 95%CI:-6.09 to -3.16), fasting blood glucose (MD=-24.59, 95%CI:-28.80 to -20.37), and HbA1c (MD=-0.94, 95%CI: -1.09 to -0.79), while fasting insulin was not significantly changed (MD = 1.21, 95%CI: -0.77 to 3.19).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Orforglipron was developed for antidiabetic and anti-obesity potential.
Research context only—not evidence of a treatment effect.
- IUPHAR ligand commentary
Oforglipron (LY3502970) is an oral, nonpeptide glucagon-like peptide-1 receptor (GLP-1R) agonist that was developed for antidiabetic and anti-obesity potential
1 cited source · 1 linked study ID
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record.
Mean body-weight change at week 72 was -7.5% with 6 mg orforglipron vs -2.1% with placebo.
Research context only—not evidence of a treatment effect.
- Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment.
The mean change in body weight from baseline to week 72 was -7.5% (95% confidence interval [CI], -8.2 to -6.8) with 6 mg of orforglipron, -8.4% (95% CI, -9.1 to -7.7) with 12 mg of orforglipron, and -11.2% (95% CI, -12.0 to -10.4) with 36 mg of orforglipron, as compared with -2.1% (95% CI, -2.8 to -1.4) with placebo (P<0.001 for all comparisons with placebo).
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Orforglipron is also known as LY-3502970 (including capitalization variants).
Research context only—not evidence of a treatment effect.
- ORFORGLIPRON
LY-3502970; Ly3502970; LY3502970; Orforglipron
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Orforglipron is described as an oral agent among emerging therapies.
Research context only—not evidence of a treatment effect.
- Childhood obesity and cardiac risk in youth: Emerging challenges toward 2050.
Emerging therapies including cagrilintide plus semaglutide, oral agents such as orforglipron and danuglipron, and the triagonist retatrutide
1 cited source · Study independence not established
How to read this evidence
Sources and study IDs describe provenance, not clinical strength. Several articles can report the same study; one study can support several distinct findings. No clinical strength rating has been assigned here.
1 cited passage across 1 source record. 1 publication group(s) lack a resolved study identity.
Orforglipron is a small molecule in ChEMBL (ID: CHEMBL4446782).
Research context only—not evidence of a treatment effect.
- ORFORGLIPRON
ChEMBL ID: CHEMBL4446782 Preferred name: ORFORGLIPRON Molecule type: Small molecule
Research status + gaps
What still needs better answers?
- Not yet covered in this profile: administration, contraindications, interactions, regulatory status, safety.
- Some extracted findings are not shown because they did not pass Peplexicon's automated evidence checks.
These are the limits of this profile, not an exhaustive list of scientific uncertainties.
References + discovery
Open the records yourself.
- ChEMBL activities for CHEMBL4446782 ↗
chembl-activities · published August 28, 2026 · retrieved August 28, 2026
- ORFORGLIPRON ↗
chembl-molecule · published August 28, 2026 · retrieved August 28, 2026
- Metabolic and Glycemic Effects of Orforglipron, a <scp>GLP</scp> ‐1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta‐Analysis of Randomised Clinical Trials ↗
doi · published July 1, 2026 · retrieved September 9, 2026
- Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. ↗
doi · published June 23, 2023 · retrieved September 8, 2026
- Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. ↗
doi · published September 16, 2025 · retrieved September 8, 2026
- Orforglipron ( <scp>LY3502970</scp> ), a novel, oral non‐peptide glucagon‐like peptide‐1 receptor agonist: A Phase 1a, blinded, placebo‐controlled, randomized, single‐ and multiple‐ascending‐dose study in healthy participants ↗
doi · published June 21, 2023 · retrieved September 8, 2026
- The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron ↗
doi · published December 18, 2024 · retrieved September 9, 2026
- IUPHAR ligand commentary ↗
iuphar-comments · published August 28, 2026 · retrieved August 28, 2026
- Safety and efficacy of the new, oral, small-molecule, GLP-1 receptor agonists orforglipron and danuglipron for the treatment of type 2 diabetes and obesity: systematic review and meta-analysis of randomized controlled trials. ↗
pubmed · published December 1, 2023 · retrieved September 9, 2026
- Orforglipron, a novel non-peptide oral daily glucagon-like peptide-1 receptor agonist as an anti-obesity medicine: A systematic review and meta-analysis. ↗
pubmed · published April 1, 2024 · retrieved September 9, 2026
- The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron. ↗
pubmed · published December 18, 2024 · retrieved September 8, 2026
- Disposition and Absolute Bioavailability of Orally Administered Orforglipron in Healthy Participants. ↗
pubmed · published January 1, 2026 · retrieved September 9, 2026
- Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. ↗
pubmed · published November 6, 2025 · retrieved September 8, 2026
- Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. ↗
pubmed · published December 20, 2026 · retrieved August 28, 2026
- Engineered nutrient-stimulated hormonal multi-agonists for precision targeting of obesity and metabolic disorders. ↗
pubmed · published April 1, 2026 · retrieved September 2, 2026
- The efficacy and safety of danuglipron and orforglipron in patients with type 2 diabetes and obesity: a systematic review and meta-analysis. ↗
pubmed · published January 1, 2025 · retrieved September 3, 2026
- Efficacy and Safety of Oral GLP-1 RA Orforglipron on Weight and Glycemic Control According to Diabetes Status: A Systematic Review and Meta-Analysis. ↗
pubmed · published August 1, 2026 · retrieved September 5, 2026
- Orforglipron: A Comprehensive Review of an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity and Type 2 Diabetes. ↗
pubmed · published January 30, 2026 · retrieved September 9, 2026
- Childhood obesity and cardiac risk in youth: Emerging challenges toward 2050. ↗
pubmed · published June 1, 2026 · retrieved August 26, 2026
- Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators, perspectives and controversies. ↗
pubmed · published June 1, 2026 · retrieved August 25, 2026
- Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial. ↗
pubmed · published July 1, 2026 · retrieved September 5, 2026
- Small-Molecule Oral Versus Injectable Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists: Comparative Efficacy, Safety, and Future Clinical Perspectives. ↗
pubmed · published April 1, 2026 · retrieved September 12, 2026
- Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison. ↗
pubmed · published August 1, 2026 · retrieved September 8, 2026
- Orforglipron Added to Titrated Insulin Glargine in Type 2 Diabetes: The ACHIEVE-5 Randomized Clinical Trial. ↗
pubmed · published August 4, 2026 · retrieved August 28, 2026
- Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial. ↗
pubmed · published July 11, 2026 · retrieved September 5, 2026
- Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials. ↗
pubmed · published September 1, 2026 · retrieved September 2, 2026
- Orforglipron for the treatment of moderate-to-severe obstructive sleep apnea in adults with obesity or overweight: Study design and baseline characteristics of ATTAIN-OSA, a phase 3 trial. ↗
pubmed · published August 1, 2026 · retrieved August 20, 2026
- Comparative Positioning of Orforglipron Among Selected GLP-1 Receptor Agonist Benchmarks: A Narrative Review. ↗
pubmed · published June 1, 2026 · retrieved August 26, 2026
- Mechanistically resolved prediction of compound hepatotoxicity using primary human liver spheroids-Application to recent real-world cases. ↗
pubmed · published August 1, 2026 · retrieved August 27, 2026
- Variant-specific pharmacophoric shifts in glucagon-like peptide-1 receptor-orforglipron complexes revealed by Boltz-2 co-folding and membrane molecular dynamics. ↗
pubmed · published September 1, 2026 · retrieved September 5, 2026
- Orforglipron: First Approval. ↗
pubmed · published July 21, 2026 · retrieved September 5, 2026
- Investigation into the efficacy and safety profile of oral small-molecule GLP-1 receptor agonists in type 2 diabetes and obesity: a systematic review and meta-analysis. ↗
pubmed · published January 1, 2026 · retrieved August 26, 2026
- Metabolic and Glycemic Effects of Orforglipron, a GLP-1 Receptor Agonist, in Adults With or Without Diabetes: A Network Meta-Analysis of Randomised Clinical Trials. ↗
pubmed · published July 1, 2026 · retrieved September 5, 2026
- Orforglipron, a Small-Molecule Glucagon-like Peptide-1 Receptor Agonist (GLP-1RA), Has Neuroprotective and Anti-Inflammatory Effects. ↗
pubmed · published July 21, 2026 · retrieved September 5, 2026
- The role of GLP-1 and GIP receptor agonists in the treatment of diabetes and obesity. ↗
pubmed · published September 1, 2026 · retrieved August 27, 2026
- Integrating glucagon-like peptide-1 receptor agonists into dermatology practice: Safety and monitoring strategies. ↗
pubmed · published August 6, 2026 · retrieved September 12, 2026
- Role of Oral Glucagon-Like Peptide-1 Receptor Agonists in Weight Management for Individuals With Overweight or Obesity Without Diabetes: A Network Meta-Analysis of Randomized Controlled Trials. ↗
pubmed · published August 1, 2026 · retrieved August 18, 2026
- Orforglipron for obesity treatment in older patients ≥65 years with or without type 2 diabetes: A post hoc subgroup analysis of the ATTAIN-1 and ATTAIN-2 trials. ↗
pubmed · published September 1, 2026 · retrieved August 28, 2026
- Potential nephroprotective mechanisms of orforglipron, an oral non-peptide GLP-1 receptor agonist. ↗
pubmed · published January 1, 2026 · retrieved August 22, 2026
- Oral Incretin-Based Therapies for Weight Management. ↗
pubmed · published September 4, 2026 · retrieved September 5, 2026
Publication history and provenance
Version 17 · Automated assessment · September 12, 2026
91b56a994ec65298e04dbcdbb362dccf75b8cfb70f285337c5cc2591170a923e