From rats to people: how a peptide earns its evidence

1. 0:00“It worked in rats.” You'll hear that about a lot of peptides. Here's what it really tells you.
2. 0:07Evidence climbs a ladder: lab experiments, then animals, then small reports in people, then randomized trials with a placebo group, then reviews that combine many trials.
3. 0:19How many climb all the way? One study followed a hundred and one highly promising lab discoveries. Twenty-seven reached a randomized trial. Five were licensed. Only one came into wide use.
4. 0:31Today, about one in ten drugs entering human testing wins FDA approval. For peptides that started trials between twenty eleven and twenty twenty, about eight in a hundred.
5. 0:44Animal results can even point the wrong way. A stroke drug called tirilazad cut brain damage by twenty-nine percent in animals, and was linked to worse outcomes in patients.
6. 0:54That's why the FDA wants control groups. Its rules name three things a trial must separate from a drug's effect: spontaneous change, the placebo effect, and biased observation.
7. 1:06In the big semaglutide trial, people on the drug lost fourteen point nine percent of their body weight. The placebo group lost two point four. So the drug's extra effect was twelve point four points.
8. 1:19The GLP-1 family climbed every rung. The hormone was found in a gene in nineteen eighty-three. In nineteen eighty-seven it released insulin in rat and pig pancreas, and in seven volunteers. The first medicine arrived in two thousand five, and later trials followed thousands of people.
9. 1:37Where does BPC-157 stand? Many animal studies, mostly from one research group. About eighty people, in five small studies. One controlled trial, with no significant difference. And no approval.
10. 1:52A ladder isn't a verdict, it's a map. See where every peptide stands, at peplexicon.com.

Sources

1. OCEBM Levels of Evidence Working Group. The Oxford 2011 Levels of Evidence (table, v2.1)
2. FDA. The Drug Development Process (content current 01/04/2018)
3. FDA. Step 3: Clinical Research (content current 01/04/2018)
4. 21 CFR §314.126, Adequate and well-controlled studies
5. Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014;32:40–51.
6. BIO, Informa Pharma Intelligence, QLS Advisors. Clinical Development Success Rates and Contributing Factors 2011–2020. Feb 2021
7. Contopoulos-Ioannidis DG, Ntzani E, Ioannidis JP. Translation of highly promising basic science research into clinical applications. Am J Med. 2003;114:477–484.
8. Perel P, et al. Comparison of treatment effects between animal experiments and clinical trials: systematic review. BMJ. 2007;334:197.
9. Hróbjartsson A, Gøtzsche PC. Placebo interventions for all clinical conditions. Cochrane Database Syst Rev. 2010;CD003974.
10. Bell GI, Sanchez-Pescador R, Laybourn PJ, et al. Exon duplication and divergence in the human preproglucagon gene. Nature. 1983.
11. Mojsov S, Weir GC, Habener JF. Insulinotropin: GLP-I (7-37) … potent stimulator of insulin release in the perfused rat pancreas. J Clin Invest. 1987.
12. Holst JJ, Orskov C, Nielsen OV, et al. Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut. FEBS Lett. 1987.
13. Kreymann B, Williams G, Ghatei MA, et al. Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet. 1987.
14. Marso SP, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER). N Engl J Med. 2016.
15. Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021.
16. Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med. 2023.
17. FDA briefing document, BPC-157, Pharmacy Compounding Advisory Committee, Jul 2026
18. Byetta (exenatide) prescribing information, 2005