🦎 From Gila Monsters to Game-Changing Drugs — The Hidden Power of Venom

By Prof. Nelly Pitteloud

By any measure, Ozempic has been a pharmaceutical blockbuster. Originally developed for type 2 diabetes and now famous for its weight-loss effects, it has found its way into medicine cabinets around the world, generating billions in annual sales. But behind this medical marvel is a venomous lizard from the desert.

The Gila Monster: A Reclusive Lizard with Hidden Potential

Meet the Gila monster, a chunky, slow-moving reptile native to North America. Known for its toxic bite and sluggish metabolism, this desert dweller eats just a handful of times each year, thanks in part to a hormone in its venom that slows digestion. That very hormone inspired the development of GLP-1 receptor agonists — the class of drugs that includes Ozempic.

In 1980, a chance collaboration between gastroenterologist Jean-Pierre Raufman and chemist John Pisano led to the discovery of a peptide in Gila monster venom that would revolutionize diabetes care. Their curiosity-driven research uncovered exendin-4, a molecule similar to a human hormone that regulates insulin, but with longer-lasting effects. Though initially overlooked, endocrinologist John Eng later recognized its potential and helped turn it into exenatide (Byetta®), the first in this new class of drugs for type 2 diabetes.

These so-called GLP-1 receptor agonists — now widely known by names like Ozempic, Wegovy, and Mounjaro — not only manage blood sugar but also promote significant weight loss and may protect against heart, kidney, and brain diseases. Today, they are also considered one of the most promising tools in the treatment of obesity, a condition that affects over 650 million adults globally.

The Discovery of Exendin-4: A Diabetes Game-Changer

In the 1990s, Dr. John Eng, a brilliant endocrinologist at the Veterans Administration Center in New York, stumbled upon something extraordinary. While researching hormones in the Gila monster’s venom, Dr. Eng identified a peptide that closely resembled a human hormone called GLP-1. This peptide, known as exendin-4, was found to stimulate insulin production in a way that could significantly benefit people with type 2 diabetes.

GLP-1 normally triggers insulin release in response to food, but lasts in the body for only about two minutes. Exendin-4, on the other hand, remains active for hours, making it a potentially game-changing solution for long-term blood sugar control.

From Research to Reality: Exenatide (Byetta®)

Thanks to the work of Dr. Josephine Egan and colleagues, the synthetic form of exendin-4, called exenatide, made its way into clinical practice. After a series of promising trials on diabetic mice, exenatide was found to effectively regulate blood glucose levels in humans — boosting insulin production and protecting pancreatic beta cells.

By 2005, the FDA approved Byetta® for the treatment of type 2 diabetes. But during clinical use, researchers noted an unexpected benefit: patients were losing weight. This observation opened the door to exploring GLP-1 agonists as a treatment for obesity, not just diabetes.

Exendin-4: A Possible Treatment for Alzheimer’s and Other Brain Diseases

As scientists dug deeper into the effects of exendin-4, they discovered its promise went beyond metabolic health. GLP-1 and its analogs like exendin-4 encourage the growth of new neurons and protect mature ones from damage — key functions in the fight against neurodegenerative conditions like Alzheimer’s and Parkinson’s disease.

In mouse models of Huntington’s disease, for example, exendin-4 reduced the accumulation of toxic huntingtin protein, improved motor function, and even extended survival. In studies of Alzheimer’s, it lowered levels of amyloid-beta, a protein implicated in the disease’s progression, suggesting it could act as a neuroprotective agent.

A New Model for Drug Discovery: One Molecule, Many Diseases

The discovery of exendin-4 is a powerful reminder that some drugs may have wide-ranging effects beyond their original targets. As Dr. Egan puts it:

“Instead of ‘one drug, one disease,’ we should think of designing drugs that impact multiple diseases.”

GLP-1 receptor agonists are a perfect example — originally designed to treat type 2 diabetes, they are now transforming how we approach obesity, cardiovascular disease, and brain health.

Nature’s Bounty: What Other Secrets Are Hiding?

From ancient herbal remedies to penicillin, the natural world has long been a source of healing. The Gila monster now joins that legacy — not just as a venomous oddity, but as a symbol of nature’s untapped potential in medicine.

As researchers continue to study exendin-4 and other naturally derived compounds, one thing is clear: the solutions to our most pressing health challenges might just be hiding in the most unlikely places.