Show Notes
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. I understood obesity clinically. Then I understood it personally. In one version of my career, revision surgery remains the answer for weight regain. In this version, I reached for GLP-1 therapy instead. Today, I weigh what I weighed when Nixon was president. I am both surgeon and patient. And your reporter.
A Necessary Caution GLP-
More from Fork U with Dr. Terry Simpson
With all the spices we have access to, it is amazing how bland recipes have become. I have many cookbooks, some from great chefs, television personalities, and friends. What I am always surprised by is how bland the food has become. People seem to think a bit of salt, pepper, maybe onions, and garlic provide the spices one needs. Perhaps it is because some associate spice with heat. Mostly because many have never experimented with some of those great warm spices available. A pinch of coriander, some freshly ground cumin, a little cardamom, or a touch of cinnamon can turn an ordinary dish into something remarkable. And the most astonishing part is that these spices financed voyages around the world, built cities, created fortunes, and caused people to kill one another. Without the spice trade, it is safe to say that the United States, as we know it, would be vastly different from what it is now. The money loaned to the United States, when we were a fledgling country, came from the wealthy spice merchants from what was considered one of the great hyperempires of the world, based in Amsterdam. But before we go to the birth of the United States, let me take you to the meatball.
Tea: The Drink That Built an Empire—and Helped Break One China had the tea. Britain had the appetite. John Hancock had a business to protect.
MesoAmerica and Chocolate In our series looking at foods that built civilizations, today we are going to stay in the Americas with chocolate. Chocolate has been used as currency, consumed by kings, incorporated into religious ceremonies, and prescribed as medicine. Today, it is a multibillion-dollar industry that wants you to believe that eating chocolate is an act of preventive cardiology. I mean, why not? They convinced us to give chocolate to people we love, eat it when we are happy, when we are sad, when only the dog understands us. Don’t feed chocolate to your dog. And we have done all this with a bitter seed that most of us would probably spit out if we tasted it straight from the tree.
I’ve been doing a series about foods that built civilizations. In this episode, we are talking about the potato. It is difficult to imagine that thousands of years ago, people constructed large buildings, managed rivers, built monuments, and created art. We have glimpses of these civilizations through stories, archaeology, and the structures they left behind, but much of their history has been lost. Imagine, we don’t even know where Cleopatra or Alexander the Great are buried, yet we know their stories. As European powers conquered Indigenous peoples, their languages, cultures, and oral traditions were suppressed. When a language disappears, so are the stories preserved within it. Our clues come from archaeology when we uncover a monument, a building, or an ancient settlement. In the Andes, the potatoes they cultivated were not the Russets, Yukon Golds, or fingerlings you find in the store today. Different colors, shapes, and textures. Adapted to survive the elevations, temperatures, and growing conditions. Biodiversity protected their food supply against frost, disease, and changing environmental conditions. If one variety failed, another might survive. The ancient wisdom of diversity that Andean farmers developed over thousands of years was lost when the potato eventually reached Ireland.
In our series about foods that built civilization, we talked a lot about grains, from wheat to corn to rice. Today, we are taking you to the ocean, with the civilizations that salmon built. From California to the interior of Alaska, salmon, a staple, allowed people to settle into villages, develop complex social networks, art, and trade routes. Those trade routes are as large as the ones in the Mediterranean. Some tribes built communal homes and developed complex art and language. Some were Seafaring tribes with canoes up to 60 feet long that traveled across oceans. All because there was a fish that would return in large numbers to streams and rivers, reliably, predictably. So predictable, the people could build their lives around salmon runs. So much so that some built a calendar not only with lunar cycles, but also with the return of the salmon. Civilizations have always gathered around food and water. The Mediterranean connected people who grew wheat and olives, giving people time to make wine, mine copper, build ships, trade with their neighbors, and occasionally go to war with them. Asia had rice and grain near the great river systems. The reliable calories from rice and grains allowed villages to become cities and to travel by water to trade. Today we are going to my home, from the Ventura River in California to my home state of Alaska.