From Gila Monster to GLP-1 Revolution

Meanwhile, in a Laboratory

In 1990, researchers isolated a peptide from Gila monster venom. Two years later, work from the Bronx VA Medical Center described exendin-4, a molecule that resembled human GLP-1 but lasted far longer in circulation.

Human GLP-1 survives only minutes before the body breaks it down. Exendin-4 resisted that breakdown. That difference changed everything.

Soon afterward, the first GLP-1 receptor agonist reached patients under the brand name Byetta. At the time, physicians used it to treat diabetes. No one called it a weight-loss drug. No one predicted it would reshape obesity medicine.

And yet, the foundation was already in place.

While I Was Operating

At the Phoenix Indian Medical Center, I performed weight loss surgery in a population with some of the highest rates of type 2 diabetes in the world. Researchers there studied metabolism intensely. The “thrifty gene” hypothesis gained traction in that environment. Scientists asked whether efficient energy storage, once protective in scarcity, became harmful in abundance.

At the same time, I watched something remarkable in the operating room. After gastric bypass, patients’ blood sugars often improved within days, before meaningful weight loss occurred. Hormones were shifting. Physiology was driving outcomes.

Meanwhile, GLP-1 drugs evolved.

Researchers lengthened their half-lives. Chemists modified their structures so they bound albumin and stayed active for days rather than minutes. Clinical trials expanded. Safety data accumulated.

Eventually, semaglutide showed average weight loss approaching fifteen percent of body weight in obesity trials. Then tirzepatide, now marketed as Zepbound for obesity, exceeded 20 percent weight reduction in higher-dose studies. In addition, cardiovascular outcome trials demonstrated reductions in major adverse cardiac events in high-risk patients.

These were not cosmetic results. These were metabolic and cardiovascular outcomes.

Food Noise

Patients rarely talk about receptors. They talk about noise.

Food noise.

The constant internal dialogue about eating. The mental pull toward the pantry. The background chatter that never quite stops.

GLP-1 receptors exist in appetite-regulating areas of the brain, including the hypothalamus and brainstem. These medications act through vagal signaling and through regions where the blood-brain barrier is more permissive. As a result, they modulate satiety and reward pathways.

Consequently, many patients report something simple but profound: the noise quiets.

Not disappears. Quiet.

That distinction matters.

Diet Culture Pushback

Predictably, not everyone celebrates this shift.

Diet culture thrives on the belief that weight reflects character. Some coaches insist the solution is fewer calories. Others argue for more beef, more butter, more fiber, or stricter discipline. Entire industries depend on the idea that trying harder solves everything.

However, biology does not negotiate with virtue.

Obesity is a chronic, relapsing, neurohormonal disease. No one worked harder at weight loss than many of my surgical patients. Likewise, I do not lack willpower. And I practice culinary medicine. Preaching and eating a Mediterranean diet.

Nevertheless, effort alone does not silence dysregulated signaling.

Calling GLP-1 therapy “cheating” misunderstands the science. These medications restore signaling. They amplify satiety. They reduce excess reward drive. They support physiology.

That is treatment, not moral compromise.

My Parallel Universe

When I began my career, I weighed about 185 pounds. Years later, hospital cafeterias, exhaustion, and irregular meals pushed me to 225.