How Gila Monsters Changed the World by Angela Rieck

GLP-1s (glucagon-like peptide-1) are game changing weight loss and diabetes drugs. An estimated 1 in 8 American adults (12%) are currently taking GLP-1 medications (such as generic GLP-1s, Ozempic, Wegovy, or Mounjaro) for weight loss, diabetes, kidney disease, or heart conditions. In total, nearly 20% of adults have taken them at some point. These medications were initially prescribed to help people with type 2 diabetes manage their blood sugar. When weight loss was recognized as a side effect, physicians began prescribing them for weight loss. As research pours in, they have potential for kidney diseases, heart diseases, anxiety, and depression.

GLP-1 drugs mimic the naturally occurring GLP-1 gut hormone and amplify its effects. This hormone decreases blood sugar levels and slows down the stomach. More importantly, it suppresses hunger signals by signaling the hypothalamus, known as the appetite center of the brain. People taking these drugs experience little or no hunger.

The success of GLP-1 drugs for weight loss is consequential. And in most cases, GLP-1 drugs are prescribed alongside lifestyle changes, like a healthy diet and physical activity, to help patients lose weight and maintain their weight long-term. Numerous clinical studies have shown they can help patients lose weight (between 17% to 28% of body weight) more effectively and maintain a healthy body weight (if they continue to take them). The use of GLP-1s has resulted in a 20% reduction in cardiovascular diseases, reduced fatty liver disorder, and reduced instances of type 2 diabetes. GLP-1s are being explored for reducing depression and anxiety.

But how did scientists discover these drugs? 

From research on a lizard.

If we encounter a Gila monster, our first instinct should be to back away. Chunky, heavy-scaled, and patterned like a Halloween decoration, Heloderma suspectum (the Gila monster) is one of the few venomous lizards on Earth. Its bite is notoriously painful, delivering a slow-churning neurotoxin through grooved teeth rather than hollow fangs.

But the Gila monster saliva has transformed 21st-century medicine through scientific research and research by the pharmaceutical industry. The story of GLP-1s and the Gila monster is a masterclass in evolutionary biology, basic research, chemical detective work, and the untapped chemicals hidden in the natural world.

The lizard holds the key to human metabolic health because of how it lives. Gila monsters are notoriously lazy eaters. They spend up to 95% of their lives underground in burrows, emerging only a few times a year in the spring to gorge themselves on bird eggs, newborn rabbits, and mice.

When they eat, they mean business—consuming up to one-third of their entire body weight in a single sitting. For a mammal, a sudden metabolic spike like that would cause a dangerous, chaotic surge in blood sugar. But hidden inside the Gila monster’s salivary glands is a specific hormone that switches on its digestive system, signaling its pancreas to release insulin, slow down stomach emptying, and smoothly process the sudden influx of nutrients.

Once the meal is digested, the hormone switches off, and the lizard safely sinks back into its metabolic slumber for months.

For decades, human endocrinologists were trying to solve a parallel problem. Humans naturally produce a hormone called GLP-1 that does exactly what the Gila monster’s saliva does. It notifies the pancreas to secrete insulin when blood sugar levels rise.

Synthetic human GLP-1 would be the ultimate treatment for Type 2 diabetes and support weight loss. There was just one massive roadblock: the human body destroys its own GLP-1 in less than two minutes thanks to an enzyme called DPP-4. To use natural human GLP-1 as a drug, a patient would need a continuous, 24-hour intravenous drip.

In the late 1980s and early 1990s, Dr. John Eng, a clinical researcher at the Veterans Affairs Medical Center in the Bronx analyzed the saliva of the Gila monster and discovered a protein that he named exendin-4.

Structurally, exendin-4 looked remarkably like human GLP-1—sharing about 53% of its amino acid sequence. But it was immune to human DPP-4 enzymes. Because the Gila monster needed a hormone that could survive long enough to process a massive meal over many hours, nature had built a molecular fortress. When injected into mammals, exendin-4 stuck around for hours.

Recognizing the monumental potential of this lizard protein, Dr. Eng tried to get pharmaceutical companies interested, but many passed, viewing the idea of a lizard-venom diabetes drug as too eccentric. Undeterred, he patented the molecule himself. Eventually, a biotech company named Amylin Pharmaceuticals took the gamble.

Scientists synthesized the lizard’s peptide into a drug called exenatide. In 2005, the FDA approved it under the brand name Byetta—the world’s very first GLP-1 receptor agonist.

Byetta required twice-daily injections, but it worked. Not only did it help Type 2 diabetics regulate their blood sugar safely (only triggering insulin production when blood sugar was actually high, preventing dangerous crashes), but patients also started reporting they were losing weight. By slowing gastric emptying and signaling the brain that the body was full, the lizard-originated molecule fundamentally changed our relationship with food.

Once the Gila monster proved that the GLP-1 pathway was a viable medical target, pharmaceutical giants poured billions into refining the molecule. Scientists began engineering longer-lasting variations that mimicked the lizard’s trick but were closer to human code. This line of research resulted in the weekly injections that we see dominating the headlines today: Zepbound, Wegovy, Mounjaro, and generic GLP-1’s.

What started as a biochemical curiosity tucked inside the jaw of a protected lizard in the Arizona desert evolved into a multi-billion-dollar medical revolution that is rewriting obesity treatment, aiding in kidney disease, and saving millions from the cardiovascular complications of diabetes.

So the ugly Gila monster has proved to be a pathway to one of the world’s most important drugs. What other life-changing discoveries are hidden in nature?