From lizard venom to a weekly shot

1. 0:00Today's GLP-1 medicines trace back, in part, to a desert lizard.
2. 0:05In the early 1980s, scientists reading the glucagon gene found a surprise: a second, glucagon-like peptide. They called it GLP-1.
3. 0:16In 1987, three research teams showed that a trimmed form of GLP-1 powerfully releases insulin.
4. 0:23But it vanished from the blood in about two minutes, too fast to be a practical medicine.
5. 0:29Then, in 1992, researchers studying Gila monster venom found exendin-4: a peptide that switches on the same receptor, and resists the enzyme that breaks GLP-1 down.
6. 0:41A synthetic copy, exenatide, became the first GLP-1 medicine in 2005, as a twice-daily shot.
7. 0:48Chemists then rebuilt human GLP-1 to last longer: liraglutide, once a day, in 2010, and semaglutide, once a week, in 2017.
8. 0:59Today the family includes daily pills, and molecules that copy two or three signals at once, some still in trials.
9. 1:07In 2024, the scientists behind GLP-1 medicines won a Lasker Award. The whole story, with sources, is at peplexicon.com.

Sources

1. Bell GI et al. Exon duplication and divergence in the human preproglucagon gene. Nature. 1983
2. Mojsov S et al. Insulinotropin: glucagon-like peptide I (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin release. J Clin Invest. 1987
3. Holst JJ et al. Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut. FEBS Lett. 1987
4. Kreymann B et al. Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet. 1987
5. Eng J et al. Isolation and characterization of exendin-4 from Heloderma suspectum venom. J Biol Chem. 1992
6. Drugs@FDA: Byetta, NDA 021773
7. Drugs@FDA: Victoza, NDA 022341
8. Drugs@FDA: Ozempic, NDA 209637
9. Lasker Foundation: 2024 Lasker~DeBakey Clinical Medical Research Award, GLP-1-based therapy for obesity