When scientists first discovered the insulin secretion effects of gut hormone GLP-1 in the 1980s, it seemed like the automatic gateway toward a landmark diabetes treatment. GLP-1, or glucagon-like peptide-1, slows digestion, signals the pancreas to release insulin, and even makes you feel full after a meal. If that peptide could be turned into a medication, experts theorized, GLP-1 could revolutionize pharmaceuticals.

But there was one major problem stumping researchers: GLP-1 lasted mere minutes in the body. Bodily hormones quickly break down both naturally produced and synthetic GLP-1, and that left drug developers unable to determine if a consistent dose of the peptide could effectively regulate insulin. It seemed, at the time, that GLP-1 was the miracle hormone that vanished too fast in the body to even be useful as a medication.

What GLP-1 lacked, however, is what another peptide had.

Enter exendin-4, composed of 39 amino acids and a close match to the sequence of GLP-1. As told in this Popular Mechanics feature, researcher Jean-Pierre Raufman and endocrinologist John Eng discovered exendin-4 in the 1990s in the most unlikely of places: the venom of the thick-skinned Gila monster. Turns out, the venom proved useful as a blood sugar and appetite regulator. Raufman’s years of studying animal toxins led to the uncovering of exendin-4 and eventual production of type 2 diabetes drug Byetta—and it’s a breakthrough that kick-started the entire GLP-1 drug industry.

So what made this peptide from lizard venom so effective? Unlike GLP-1 at the time, which would get chewed up rapidly by enzymes in the human body, exendin-4 caused blood glucose to drop to a normal level—and stay there for hours, or even days. That’s because humans and other species outside the Gila monster hadn’t evolved alongside the venom-derived peptide—and, therefore, couldn’t degrade it.

“When you have a peptide from a different species, you may not have the peptidase, the hormone that degrades it,” Andrew Young, former vice president of research at Byetta producer Amylin Pharmaceuticals, explained in our feature. “The Gila monster had done what the industry had been unable to do for about a decade.”

Studies on diabetic rats, mice, and monkeys continued to show consistent results. Exendin-4, like GLP-1, triggered insulin secretion from the pancreas and slowed digestion. But it stayed in the bloodstream for hours—not minutes, like GLP-1—and that longer half-life ultimately intrigued drug developers.

After rounds of successful human clinical trials came the production of exenatide, exendin-4’s synthetic version. And in 2005, Byetta was born, becoming the first GLP-1 agonist approved by the FDA. Hundreds of thousands of Americans turned to the twice-daily injection for regulating glucose, and many even lost weight on the drug.

Experts would eventually find the solution to make synthetic GLP-1 last longer in the body, and GLP-1 medication production took off with the FDA approval of Victoza (2010), Ozempic (2017), and Wegovy (2021). But without the creation of Byetta thanks to some Gila monster venom, who’s to say what would’ve come about for the now-booming GLP-1 drug industry?

For more on the venomous genesis of GLP-1 drugs, and the race to create even more effective diabetes and weight loss medications, read Pop Mech’s full story now.