A Brief History of GLP-1 Medications: From Diabetes Drug to Blockbuster Weight Loss Treatment

The story of GLP-1 medications is one of the more fascinating in modern medicine. It starts with a Gila monster, winds through decades of diabetes research, and ends up reshaping how the world thinks about obesity. Here’s the full journey.

It Started With Lizard Spit

In the 1980s, scientist John Eng was studying the venom of the Gila monster, a large, venomous lizard native to the American Southwest. He discovered a compound in the venom called exendin-4 in 1992 that closely mimicked the effects of GLP-1 in humans. Unlike natural GLP-1, which breaks down in minutes, exendin-4 lasted much longer in the body.

That discovery eventually led to exenatide (Byetta), the first GLP-1 medication approved by the FDA (for type 2 diabetes) in 2005. It required twice-daily injections and had modest effects compared to what came later, but it proved the concept worked.

The Semaglutide Breakthrough

The real game-changer came from Novo Nordisk, a Danish pharmaceutical company that had been working on GLP-1 medications for years. They developed semaglutide, a GLP-1 agonist designed to last a full week with a single injection. It was approved as Ozempic^® for type 2 diabetes in 2017.

Then something unexpected happened: The weight loss in clinical trials was remarkable. People were losing 10%, 15%, even more of their body weight. That hadn’t been seen with a medication before, outside of bariatric surgery.

Wegovy^® Arrives

Novo Nordisk ran dedicated trials for semaglutide as a weight loss treatment, using a higher dose than Ozempic^®. The results were striking: Participants lost an average of about 15% of their body weight over 68 weeks. The most commonly reported side effects in clinical trials included nausea, vomiting, diarrhea, and constipation, which in most cases were mild to moderate and improved over time. In 2021, the FDA approved semaglutide under the brand name Wegovy^® specifically for chronic weight management, a watershed moment for obesity medicine.

Tirzepatide Raises the Bar

Just as Wegovy^® was becoming a household name, Eli Lilly introduced tirzepatide (Mounjaro^® for diabetes, Zepbound^® for weight loss), a drug that targets both GLP-1 and GIP receptors. Clinical trials showed even greater weight loss than semaglutide, with some participants losing 20% or more of their body weight. Zepbound^® received FDA approval for obesity in late 2023.

The Shortage and the Reckoning

The explosive demand for GLP-1 medications, driven partly by celebrity use and social media, led to widespread drug shortages that affected people who needed them for diabetes management. It also sparked serious conversations about access, insurance coverage, cost, and the ethics of using these drugs for cosmetic weight loss versus medical need.

Where We Are Now

We’re in the middle of a GLP-1 revolution. Oral versions of semaglutide are now approved. New drugs are in clinical trials. Research is expanding into cardiovascular disease, sleep apnea, kidney disease, addiction, and more. And the conversation about how to make these medications accessible to the people who need them most is far from over.

The Gila monster could not have anticipated any of this.

Writing Staff