Exenatide (Byetta /
Bydureon)

The Discovery

Diabetes Without Answers

A Growing Crisis With Shrinking Options

By the early 1990s, type 2 diabetes was spreading across America like wildfire. More than 10 million people had it, and the number was climbing every year. The treatments available were frustrating at best and dangerous at worst.

Insulin injections were the gold standard, but they caused weight gain and could make blood sugar crash to dangerously low levels. Pills like sulfonylureas pushed the pancreas harder and harder to make insulin, eventually wearing it out. Metformin helped, but many patients needed more.

Doctors were stuck. They needed a drug that could lower blood sugar without the constant risk of crashes, without causing weight gain, and ideally one that could help the exhausted pancreas recover. That drug existed — but it was hiding in the mouth of a poisonous lizard in the Arizona desert.

The Breakthrough

The Bronx Lab

A Scientist, A Catalog, and A Lizard

Dr. John Eng was an endocrinologist at the Veterans Affairs Medical Center in the Bronx, New York. He had developed a technique to screen animal venoms for new hormones — and he was looking for something no one else thought to search for.

Earlier NIH research had shown that Gila monster venom could make the pancreas enlarge. Eng was fascinated. The Gila monster is one of only two venomous lizards on Earth. It eats just three or four times a year, yet somehow keeps its blood sugar perfectly controlled between meals. Eng suspected the answer was in its venom.

He ordered dried venom samples from a serpentarium in Utah — through a mail-order catalog, of all things. Working in his modest Bronx lab, he ran his chemical screening tests. In 1992, the results came back: the venom contained a brand-new hormone he named exendin-4. It looked remarkably similar to human GLP-1 — but with one critical difference. While natural GLP-1 fell apart in the bloodstream in two minutes, exendin-4 lasted for hours. The lizard had already solved the problem that was stumping every scientist in the field.

The Trials

Nobody Wanted It

A Discovery Abandoned By Its Own Government

What happened next would frustrate Eng for years. He brought his discovery to the VA, expecting excitement. Instead, they showed no interest in patenting exendin-4. The government agency that funded his lab saw no commercial potential in a hormone from lizard spit.

So Eng took an extraordinary step: he paid for the patent himself, using his own money. Then he began knocking on doors at pharmaceutical companies. One after another, they turned him down. A diabetes drug from lizard venom? It sounded too strange, too risky.

For nearly three years, Eng struggled. Then, in 1996, at a scientific meeting in San Francisco, he pinned up a poster showing how exendin-4 lowered blood sugar in diabetic mice. A small biotech company called Amylin Pharmaceuticals — based in San Diego and already working on a similar gut hormone called amylin — saw the poster and made a deal. They would turn Eng's lizard hormone into a real drug.

Amylin created a synthetic version called exenatide, identical to the natural Gila monster peptide, and began the long, expensive process of clinical trials.

The Crisis

The Pancreatitis Shadow

Success Meets Suspicion

On April 28, 2005, the FDA approved Byetta — making exenatide the first GLP-1 drug in history. Patients injected it twice daily before meals, and the results were impressive: lower blood sugar, weight loss instead of weight gain, and far fewer dangerous blood sugar crashes than insulin.

But success brought scrutiny. In 2007, reports of acute pancreatitis — painful, sometimes deadly inflammation of the pancreas — began appearing in Byetta users. The FDA added warnings to the label. Headlines questioned whether the drug was safe. Some researchers pointed to a possible link between GLP-1 drugs and pancreatic cancer, though the evidence was thin.

Amylin Pharmaceuticals fought back with data showing the pancreatitis rate was no higher than in diabetic patients not taking the drug. But the damage to public confidence was real. The company's stock dropped. Doctors hesitated to prescribe it. The first GLP-1 drug ever approved was fighting for its reputation.

The Legacy

The Door It Opened

From Twice Daily to Once Weekly — and Beyond

Amylin didn't give up. They developed Bydureon — an extended-release version of exenatide that patients needed only once per week instead of twice daily. The FDA approved it in 2012. The convenience was a game-changer, and it proved that GLP-1 drugs could be redesigned for easier use.

But exenatide's greatest legacy isn't the drug itself — it's what it proved was possible. By showing that a GLP-1 drug could safely lower blood sugar, cause weight loss, and avoid dangerous crashes, Byetta opened the floodgates. Liraglutide (Victoza) followed. Then semaglutide (Ozempic, Wegovy). Then tirzepatide (Mounjaro). Each one built on the foundation that a stubborn scientist in a Bronx VA hospital had laid.

In 2013, Eng received the Golden Goose Award — given to scientists whose quirky, curiosity-driven research led to major breakthroughs. The committee's message was clear: sometimes the most important discoveries come from the most unexpected places. Like the mouth of a poisonous desert lizard.

Today, GLP-1 drugs are the fastest-growing class of medicines in the world. It all started with a mail-order venom sample and a scientist who wouldn't take no for an answer.