The unlikely 30-year path from a desert lizard to the most talked-about drugs in medicine — and the small San Diego biotech that made the first bet.
A hormone-like compound in Gila monster venom turned out to resist breakdown in the body far longer than the human hormone it resembled. That durability made it druggable. A San Diego biotech called Amylin Pharmaceuticals turned it into the first approved drug in this class in 2005. Novo Nordisk and Eli Lilly spent the next two decades re-engineering the concept into the once-weekly drugs sold today as Ozempic, Wegovy, Mounjaro and Zepbound.
In the early 1990s, endocrinologist John Eng was studying Gila monster venom and noticed it contained a compound structurally similar to human GLP-1 — the gut hormone that helps regulate insulin release. The difference was staying power. Natural human GLP-1 breaks down in the bloodstream within a couple of minutes. The lizard version, which Eng named exendin-4, kept working far longer, likely an adaptation that helps the Gila monster manage digestion and blood sugar during the long stretches between meals it survives on in the wild.
Amylin Pharmaceuticals, a biotech founded in San Diego in 1987, licensed Eng's discovery and spent years developing a synthetic version called exenatide. It launched in 2005 as Byetta — the first-ever GLP-1 receptor agonist approved by the FDA, for type 2 diabetes. Byetta required twice-daily injections and never became a blockbuster on its own, but it proved the underlying concept worked in humans. Every GLP-1 drug that followed, semaglutide included, builds on that foundation.
Novo Nordisk, a Danish company with roughly a century of diabetes drug-making behind it, took the GLP-1 concept further. Through chemical modifications — including attaching a fatty acid chain that lets the molecule bind to a blood protein and resist breakdown — they developed liraglutide, approved in 2010 as Victoza, a once-daily injection. Semaglutide was the next refinement of that same engineering approach, stable enough to work with just one injection per week. It reached the market in 2017 as Ozempic, approved for type 2 diabetes.
During Ozempic's diabetes trials, researchers noticed patients losing more weight than blood sugar improvements alone would explain. The appetite-suppressing effect of GLP-1 in the brain turned out to be powerful in its own right. Novo Nordisk ran dedicated obesity trials at a higher dose, and in 2021 the same molecule was approved as Wegovy for chronic weight management — a new label for a drug that already existed.
Eli Lilly followed a parallel path with tirzepatide, a molecule that mimics not just GLP-1 but a second gut hormone, GIP. It launched as Mounjaro for diabetes in 2022 and as Zepbound for weight loss in 2023, arriving with larger average weight-loss numbers in head-to-head trials against semaglutide. See our full GLP-1 comparison for how the four drugs stack up today.
Amylin, the small San Diego company that made the first bet on a lizard's venom, was acquired by Bristol-Myers Squibb and AstraZeneca in 2012 — a decade before GLP-1 drugs became one of the most valuable drug categories in pharmaceutical history.
The research on these drugs hasn't stopped evolving either. See our piece on how baseline A1C levels may predict weight loss response to tirzepatide, a newer finding that goes beyond the traditional diabetes-control angle.