From Lizard Venom to Weight Loss Wonder: How a Diabetes Drug Became a Cultural Phenomenon

Glucagon-like peptide-1 (GLP-1) receptor agonists started as a diabetes treatment but have become a blockbuster weight-loss medication, with use surging 700% between 2019 and 2023 in the United States. The drugs work by mimicking a natural hormone that helps regulate blood sugar and appetite, and they've shown remarkable results: more than half of people taking weekly semaglutide injections lost at least 15% of their body weight over 68 weeks, compared with around 5% in those receiving a placebo.

What Started This Diabetes Revolution?

The story of GLP-1 drugs begins in an unexpected place: the Gila monster, a venomous lizard native to the deserts of Mexico and the southwestern United States. In 1984, researchers from the US National Institutes of Health discovered that this reptile could regulate its metabolism and blood sugar levels even during long periods without food. They isolated a peptide from its venom called exendin-4, which triggered the pancreas to produce and release insulin—the hormone that helps cells absorb glucose from the bloodstream after meals.

Exendin-4 resembled a human hormone called GLP-1, but with a crucial difference: while natural GLP-1 breaks down in the body within minutes, exendin-4 lasts for hours, providing a much more sustained effect on blood sugar control. This discovery led to the development of exenatide (sold as Byetta), which was approved by the US Food and Drug Administration in 2005 and earned its manufacturer Amylin around $430 million in its first year.

How Did We Get From Diabetes Treatment to Weight Loss Drug?

While exenatide was being developed, researchers at Danish pharmaceutical company Novo Nordisk took a different approach. They focused on making GLP-1 last even longer in the bloodstream by attaching a fatty-acid molecule to it. This led to liraglutide (sold as Saxenda and Victoza), which still required daily injections. To achieve a once-weekly dosage, Novo Nordisk researcher Lotte Bjerre Knudsen and her colleagues further modified the drug's structure, creating semaglutide—a long-acting, stable version of GLP-1.

The real turning point came when researchers noticed something unexpected: people taking these drugs for diabetes were also losing significant amounts of weight. A 2018 trial comparing various doses of semaglutide and liraglutide with a placebo in nearly 900 people with obesity found that between one-third and one-half of those taking semaglutide lost at least 15% of their body weight, and at least three-quarters lost more than 5%.

Novo Nordisk launched semaglutide under the brand name Ozempic in 2017 for adults with type 2 diabetes, but the weight-loss potential led to the development of Wegovy, a higher-dose version specifically for weight management. The 2021 STEP 1 trial confirmed the drug's effectiveness: more than half of participants given weekly semaglutide injections over 68 weeks achieved at least 15% weight loss.

Why Are Doctors Calling This a Medical Milestone?

The impact of GLP-1 drugs extends far beyond celebrity endorsements. For endocrinologist John Wilding at Aintree University Hospital in Liverpool, the results have been "astounding." He describes one patient who was diagnosed with type 2 diabetes at age 17 and by her early twenties was taking three diabetes medications and facing insulin therapy—which can cause weight gain. Instead, Wilding prescribed her a GLP-1 receptor agonist. The treatment brought her blood glucose levels down to the normal range and she lost approximately 66 pounds (about 30 kilograms). "It's totally transformed her life," Wilding explains, noting that many patients experience similarly remarkable improvements in both weight and quality of life.

The significance of this breakthrough is not lost on the medical community. "This era of drug development for obesity has the potential to be a landmark in the history of medicine," says endocrinologist Timothy Garvey at the University of Alabama at Birmingham. "I think it's on par with the discovery of insulin, the discovery of penicillin, the polio vaccine".

How Do These Drugs Actually Work?

GLP-1 receptor agonists work by binding to GLP-1 receptors found on the surface of cells throughout the human body. The drugs accomplish several things simultaneously:

• Blood Sugar Control: They stimulate the pancreas to produce and release insulin in response to rising glucose levels, helping regulate blood sugar in people with type 2 diabetes.
• Appetite Suppression: They reduce intrusive thoughts about food—what doctors call "food noise"—helping people feel satisfied with smaller portions and fewer meals.
• Sustained Action: Unlike the natural GLP-1 hormone, which breaks down in minutes, these synthetic versions last for hours or even days, providing consistent effects with less frequent dosing.
• Weight Loss: The combination of improved blood sugar control and reduced appetite leads to significant weight loss, with clinical trials showing 15% to 20% reductions in body weight for many users.

The gastrointestinal side effects are typically mild to moderate, according to the PIONEER-1 placebo-controlled study published in 2019, which showed significant improvements in blood glucose levels in people with type 2 diabetes.

What makes this development particularly important is that it addresses a problem many people with type 2 diabetes face: the difficulty of losing weight while managing their condition. Traditional diabetes medications often cause weight gain, creating a frustrating cycle. GLP-1 drugs break that cycle by simultaneously improving blood sugar control and promoting weight loss—a dual benefit that has captured both medical attention and popular interest.