Trusting your gut Trusting your gut Trusting your gut

Weight-loss and diabetes drugs like Wegovy and Ozempic are often described as breakthroughs. They help people lose weight, control blood sugar and reduce heart disease risk.

In the past two years, they have moved beyond specialty medicine into everyday conversations about weight and appetite. They also raise a deeper question: What system in the body are these drugs replacing?

Christopher Damman

As a gastroenterologist, I study how food and the gut microbiome shape metabolism. From that perspective, these medications don’t just treat disease—they restore signals that modern diets have steadily diminished.

For most of human history, appetite was not just a matter of willpower. It was regulated, in part, by a relationship between what we ate and the trillions of bacteria in our lower gut. The bacteria feed on indigestible fiber and plant compounds called polyphenols, transforming them into signals that regulate hormones for appetite and metabolism. These hormones include GLP-1, the human hormone that Wegovy and Ozempic are designed to mimic.

GLP-1 and other hormones help control blood sugar, slow digestion and tell the brain when enough is enough. Together, this system acts as a natural brake on appetite. Modern diets have weakened it.

Processed foods—engineered for shelf stability and taste—often strip away the bioactive compounds that help regulate this system. The result is a less diverse gut microbiome and weaker metabolic signaling. Calories are absorbed quickly, but the body receives fewer cues to regulate hunger and fullness. The shift may be contributing to the rise in obesity and type 2 diabetes.

Wegovy and Ozempic reinvigorate our natural brake. Mounjaro has gone a step further and combined GLP-1 with a second hormone analog derived from the upper gut called GIP. Studies are showing this combination therapy to be even more effective at promoting weight loss.

These drugs complement other measures like gastric bypass surgery that are used in more advanced cases of metabolic disease. Despite the success and prospect of these drugs to help populations that may benefit most, current prescribing practices have raised questions. Should people who are only a little overweight use these drugs? What are the risks of prescribing these drugs to children and adolescents for lifelong weight management?

For many patients, the results are transformative, but they are not without tradeoffs. Common side effects include nausea, vomiting, diarrhea and constipation; rare complications include pancreatitis and delayed stomach emptying. Some patients lose muscle, particularly in the absence of exercise. And when the drugs are stopped, weight often returns, raising further questions about long-term effects and how best to to transition back and manage weight using only lifestyle.

For those living with obesity or diabetes, these therapies can be lifesaving. But they also highlight that metabolism is not just treated, it is continuously shaped by our diets and behaviors. Despite our hopes for quick fixes, a healthy lifestyle remains an indespensible component for managing metabolic disease and overall health. This includes exercise, sleep, stress management and a balanced diet.

For the majority of individuals aiming to prevent metabolic disease, supporting the gut’s appetite controls through minimally processed foods rich in fiber and plant compounds may be one of the best routes to a healthy metabolism.

These drugs can restore signals we’ve lost. The question is whether they will lead us back to a healthier metabolism—or make it easier to live without one.

Christopher Damman is a UW Medicine doctor and an associate professor with expertise in nutrition and the microbiome.