What Does a Gila Monster Have to Do With GLP-1 Weight Loss Drugs?

Long before Ozempic and Wegovy became household names, scientists found an important clue to GLP-1 drugs in the venom of a large, slow-moving lizard.
The Gila monster, native to the deserts of the American Southwest and Mexico, can go for long periods without eating. In the early 1990s, researcher John Eng discovered that its venom contained a previously unknown peptide called exendin-4.
Exendin-4 behaved a lot like GLP-1, a hormone produced in the human gut after we eat. GLP-1 signals the pancreas to release insulin when blood sugar rises, slows the emptying of the stomach and helps regulate appetite. But natural human GLP-1 disappears from the bloodstream within minutes because an enzyme rapidly breaks it down.
Exendin-4 had a useful difference: it resisted that enzyme and remained active much longer.
Researchers realized that this unusual lizard peptide might be useful for treating diabetes. A synthetic version of exendin-4 became exenatide, approved by the FDA in 2005 under the brand name Byetta. It was one of the first drugs in the class now known as GLP-1 receptor agonists.
Today's best-known GLP-1 medicines, including semaglutide, the active ingredient in Ozempic and Wegovy, are not made from Gila monster venom. They were engineered separately to mimic human GLP-1 and remain active far longer.

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