The Lizard Venom Behind Modern Diabetes Drugs

In 1992, John Eng was an endocrinologist at the Bronx VA, and his lab had no sequencer. To get around that, he used a radioimmunoassay he had built himself to scan venoms — animals tend to weaponize hormones, so venoms are a cheap library to mine. The Gila monster, a slow-moving desert lizard that eats only a few times a year, came back interesting.

What Eng pulled out he called exendin-4. It looked structurally similar to human glucagon-like peptide-1 (GLP-1), a gut hormone that triggers insulin release after a meal. GLP-1 was already known to lower blood sugar in humans. The problem was it was useless as a drug: an enzyme called DPP-4 chews it up in about one to three minutes.

Exendin-4 wasn't an analog of GLP-1 — it's a separate peptide that happens to bind the same receptor. And critically, DPP-4 doesn't recognize it. Its half-life in humans is about 30 minutes, long enough to be injected and actually work.

Eng licensed it to Amylin, which developed it into exenatide. The FDA approved it as Byetta in 2005, the first GLP-1 receptor agonist on the market. The whole later class — liraglutide, semaglutide, the Ozempic and Wegovy that now dominate the obesity drug conversation — descends from a lineage that started because a lizard could go a month between meals and a VA hospital couldn't buy a sequencer.