GLP-1 drugs such as Ozempic and Wegovy (semaglutide), and related drugs such as Mounjaro and Zepbound (tirzepatide), have transformed the treatment of obesity and type 2 diabetes. They reduce appetite, improve blood sugar control, and can produce substantial weight loss. Semaglutide has also been shown to reduce major cardiovascular events in certain high-risk patients.
The results are impressive. But they also raise important questions. What happens when people stop taking them? How much muscle is lost along with fat? And what do these medications do—and not do—to improve underlying metabolic health?
Researchers and physicians including Robert Lustig, Ben Bikman, Nick Norwitz, and William Davis offer useful perspectives on these questions.
I think GLP-1 drugs deserve neither uncritical enthusiasm nor dismissal. The benefits are real—but so are the questions.
GLP-1 is a hormone naturally released by the intestine after eating. It helps regulate blood sugar and appetite.
Drugs such as semaglutide mimic the effects of GLP-1. They increase insulin secretion when blood glucose is elevated, reduce glucagon, slow stomach emptying, and act on areas of the brain involved in appetite. As a result, people tend to feel full sooner, experience less hunger, and eat fewer calories.
Tirzepatide works somewhat differently. It activates both GLP-1 and another hormone receptor called GIP, and has produced even greater average weight loss than semaglutide in a head-to-head trial.
These drugs do more than suppress appetite. They improve blood glucose regulation, and tirzepatide has also been shown to improve insulin sensitivity.
The important question for me is what these impressive effects mean for long-term metabolic health.
The weight-loss results from these medications are remarkable.
In major clinical trials, people taking semaglutide have lost about 15% of their body weight on average, while higher doses of tirzepatide have produced average losses of around 20% or more. For someone weighing 220 pounds, a 20% reduction would be about 44 pounds.
The benefits extend beyond the number on the scale. These medications can substantially improve blood sugar control, and studies have found improvements in several measures of metabolic health. Semaglutide has also been shown to reduce major cardiovascular events in certain people with overweight or obesity and established cardiovascular disease.
For people who have struggled unsuccessfully with obesity or diabetes for years, these are not trivial benefits. The drugs clearly work.
The more difficult question is whether weight loss and improved laboratory results tell the whole story.
The success of GLP-1 drugs has produced an interesting debate among physicians and researchers whose work I follow.
Ben Bikman acknowledges that the drugs can be very effective, but questions whether they correct the underlying metabolic problem. He argues that chronically elevated insulin may impair the body's natural GLP-1 response. The drugs can bypass that problem, he says, while reducing insulin through diet and lifestyle may address it more fundamentally.
Robert Lustig also emphasizes the distinction between weight loss and metabolic health. He believes reducing visceral and liver fat can be beneficial, but argues that improving metabolic health—not simply losing pounds—should be the goal.
William Davis is considerably more skeptical. He argues that GLP-1 drugs used for weight loss may carry important long-term disadvantages, particularly the loss of muscle and lean tissue, and believes dietary changes can address many of the underlying causes of weight gain and metabolic disease.
Nick Norwitz offers a fascinating counterpoint because he changed his mind. Initially a strong skeptic, he became much more enthusiastic after examining newer research. He now believes GLP-1 drugs may have benefits extending beyond weight loss and diabetes, potentially affecting cardiovascular health, inflammation, brain health, and other conditions.
These different perspectives raise the question I find most interesting:
Are GLP-1 drugs simply powerful weight-loss medications—or are they becoming something much more important?
GLP-1 drugs have important drawbacks as well as benefits.
One concern is loss of lean mass, including muscle, during substantial weight loss. Some lean-tissue loss normally accompanies weight loss, but preserving muscle through adequate protein and resistance exercise may be particularly important for people taking these drugs.
Common side effects include nausea, vomiting, diarrhea and constipation. More serious complications are less common.
Weight regain is another concern. In a follow-up of a major semaglutide trial, participants regained about two-thirds of their lost weight within a year of stopping treatment.
But these drugs don't simply cause weight loss. In a large tirzepatide trial, treatment also improved insulin sensitivity and pancreatic beta-cell function, with some improvement apparently independent of weight loss.
The evidence therefore suggests both substantial benefits and legitimate concerns—particularly about muscle preservation and the need for long-term treatment.
Taking a GLP-1 drug doesn't make nutrition and exercise irrelevant. In some ways, they may become even more important.
Because these drugs substantially reduce appetite, people may eat much less food. That makes it important to obtain enough protein and essential nutrients while losing weight. Resistance exercise can also help preserve muscle.
For people with insulin resistance or type 2 diabetes, reducing refined carbohydrates and ultra-processed foods may provide metabolic benefits beyond simply eating fewer calories.
This suggests that GLP-1 drugs and lifestyle changes don't necessarily have to be competing approaches. For some people, the most effective strategy may be to use the medication as a tool while also improving diet, exercise and metabolic health.
I have long believed that improving insulin resistance and metabolic health through diet and lifestyle should be a priority. The success of GLP-1 drugs doesn't change that view.
But the evidence has made me less inclined to dismiss these medications. The amount of weight loss can be remarkable, and the benefits appear to extend beyond weight loss alone.
Nick Norwitz's change of mind particularly interests me because it reflects what I try to do with health research: remain willing to change my opinion when the evidence changes.
My conclusion is that GLP-1 drugs can be extremely valuable for some people, but they should complement—not replace—attention to nutrition, exercise, muscle strength and metabolic health.
A former skeptic explains why newer evidence substantially changed his view.
A strongly skeptical perspective, particularly concerned with muscle loss and underlying metabolic health.
Explains Bikman’s argument that the drugs can work while not necessarily correcting the hyperinsulinemia he believes contributes to the problem.
Dr. Lustig discusses the benefits of GLP-1 drugs as well as his concerns about muscle loss and metabolic health.
Practical discussion of nutrition for people using GLP-1 medications.