Gila monsters are helping people lose weight

Source: Snowmanradio, Wikimedia Commons, CC BY-SA 2.0 DEED

Lately I’ve been writing about the new class of diabetes and obesity medications called GLP-1 receptor agonists, which includes Ozempic, Wegovy, and Zepbound. These drugs have gotten a ton of coverage over the last few years because they’re so good at controlling blood sugar levels and body mass, but I only recently learned that they’re based on a molecule found in Gila monster venom.

It was not at all clear to me why Gila monsters would need Ozempic (or something like it), so I asked endocrinologist Daniel Drucker from the University of Toronto — one of the discoverers of GLP-1 — to explain the connection.

Back in the 1990s, Drucker told me, endocrinologist John Eng from the Veteran Administration Center in the Bronx, New York, was fascinated by the compounds found in the venom of snakes and other reptiles because these molecules sometimes have useful medicinal properties. Anticoagulants found in snake venom, for example — which snakes use to kill people — have also inspired drugs like Integrilin, which is used to prevent heart attacks.

So Eng went prospecting in Gila monster venom, and among the compounds he found was a molecule that looked similar to the human GLP-1 molecule, which Ozempic and similar drugs mimic. Tests revealed that this new molecule, which became known as Extendin-4, functions similarly to human GLP-1, but it doesn’t break down nearly as quickly. At the time, many of the top drug companies were trying to develop a long-lived GLP-1 because they suspected it would help people control their blood sugar levels.

So Eng made the rounds of the pharmaceutical industry, and a company called Amylin Pharmaceuticals decided to give Extendin-4 a try. The compound became the basis for the first GLP-1 receptor agonist to gain FDA approval (which was called Exenatide). In the process, Gila monsters beat out some of the world’s most talented biochemists, who were all trying to design a long-lived GLP-1 on behalf of the most prestigious drug companies.

The question I had was, what do Gila monsters use Extendin-4 for in the first place? “I can only speculate because I can’t ask the lizard gods,” Drucker said. His best guess is that Gila monsters and their kin benefit from a molecule that slows how fast the stomach empties and helps get all the nutrients out of food (some of the ways Exenatide helps people regulate their blood sugar) because they only eat intermittently. Rather than eating every day, they may swallow a rat once a week or so. Extendin-4 could make these infrequent meals last as long as possible.

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