How the venom of a lizard led to one of the most important scientific discoveries of modern Medicine.

The discovery of GLP-1 (Glucagon-like peptide-1) as a potential treatment for type 2 diabetes dates back to the early 1980s. At that time, researchers were exploring the role of gut hormones in regulating blood sugar levels. GLP-1 is a hormone produced in the small intestine that stimulates insulin secretion from pancreatic beta cells, suppresses glucagon release, and slows gastric emptying.

In the early 1990s, Dr. John Eng, a researcher at the Veterans Affairs Medical Center in the Bronx, studied the venom of the Gila monster (Heloderma suspectum), a lizard native to the southwestern United States and Mexico. Eng noticed that one of the components of the venom, exendin-4, was similar in structure to GLP-1 and had similar effects on insulin secretion and blood sugar control.

Exendin-4 was subsequently synthesized and tested in animal models, where it was found to have potent effects on blood sugar control. It was also found to have a longer half-life than GLP-1, making it a promising candidate for drug development.

In 2005, the FDA approved exenatide (Byetta), a synthetic version of exendin-4, as a treatment for type 2 diabetes. Exenatide is a GLP-1 receptor agonist, which means it mimics the effects of GLP-1 by binding to and activating the GLP-1 receptor. Since then, other GLP-1 receptor agonists (GLP-1RAs), including liraglutide (Victoza), dulaglutide (Trulicity), and semaglutide (Ozempic), have been FDA-approved for use in the treatment of type 2 diabetes. Additionally, newer GLP-1RAs have been developed for obesity and are being tested for a range of disorders, owing to the versatility of this tiny peptide.

Final Word

The discovery of exendin-4 and its development into a GLP-1 receptor agonist is a prime example of how research into animal venom can lead to new drug development.

Peer review provided by Stephanie Garcia, RD

References:

National Center for Biotechnology Information. PubChem Compound Summary for CID 53396299, Exenatide. https://pubchem.ncbi.nlm.nih.gov/compound/Exenatide. Accessed Apr. 25, 2023.
Exendin-4: From lizard to laboratory...and beyond. National Institute on Aging. https://www.nia.nih.gov/news/exendin-4-lizard-laboratory-and-beyond. Accessed April 24, 2023.
Chen YE, Drucker DJ. Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard. J Biol Chem. 1997;272(7):4108-4115.