It’s hard to go a day without hearing something new about the latest diabetes and obesity medications, Semaglutide and Tirzepatide. Usually the buzz is positive, but there has been one persistent claim about these drugs that might make any potential user wary: They don’t just help you lose weight, they’re supposed to build muscle mass at the same time, making you lose weight. weak and vulnerable to all kinds of future health problems. But what does the current science say and how concerned should you be about muscle loss if you take these medications?
Semaglutide (sold under the names Ozempic and Wegovy) and tirzepatide (sold under the names Mounjaro and Zepbound) are the most recent additions to a class of drugs called incretins, which mimic hormones important for our metabolism and feeling hungry, among other functions. Semaglutide mimics GLP-1, while the new tirzepatide mimics GLP-1 and another hormone, GIP. Both medications have been shown to help people lose weight safely, reliably, and substantially more on average than diet alone or other treatments, outside of bariatric surgery. Studies have also suggested that these medications can prevent heart, kidney, and liver diseases in obese people who are vulnerable to them and perhaps even help treat the illnesses. addiction and other conditions not strictly related to obesity or diabetes.
As impressive as these medications may seem, no treatment comes without its potential drawbacks. Users will typically experience gastrointestinal issues such as vomiting and diarrhea, although these symptoms tend to improve over time. They can also cause rare but potentially serious complications, such as gastroparesisoften called stomach paralysis.
Some critics have also claimed that GLP-1 can dangerously sap our muscle mass, but experts interviewed by Gizmodo say this claim is currently not supported by the data or our understanding of how these drugs work.
Update on muscle loss and GLP-1 use
To begin with, the possibility of muscle loss while taking these medications is not surprising. Long before Ozempic appeared on the scene, doctors knew this could happen with any form of weight loss. When we lose weight, we typically lose a combination of fat mass and fat-free mass, also called lean mass, which can include our muscles. And while other aspects of GLP-1 may help us lose weight, it primarily reduces our appetite and increases our feelings of fullness, leading us to consume fewer calories over time. In other words, there’s nothing particularly new about how we lose weight by taking them.
Studies have shown that when obese people lose a lot of weight through diet alone or through bariatric surgery, 20% to 30% of this weight corresponds to lean body mass. And so far, we’re not seeing GLP-1 drugs deviate dramatically from that baseline. A 2024 report clinical trial data on semaglutide, for example, found that the proportion of lean mass lost during weight loss ranged from 0% to 40%. And large clinical trials of tirzepatide have find that the percentage of lean mass lost corresponds to the percentage lost through diet or surgery.
“So it’s really a tie,” Michael Weintraub, an endocrinologist and clinical obesity researcher at NYU Langone Health, told Gizmodo by phone. “And there’s no reason to think that there’s a unique mechanism of these GLP-1 agonists that causes some sort of specific loss of muscle mass.”
These numbers alone don’t give the complete picture either. Even with the higher numbers, obese people still lose more fat than lean mass, which is undeniably positive, says Weintraub. One of the reasons muscle loss can be dangerous is that it can make us frail and less able to perform our daily functions. But that’s absolutely not what the research shows. Compared to the placebo, people taking these drugs reported better quality of life and improved physical functioning. Some limited data also suggested that these drugs can cause a loss of lean mass without compromising the quality of our muscles.
“When I see my patients, they tell me things like, ‘Well, I feel so much better, I’m able to function so much better.’ I’m able to get on and off the subway without having to stop,” Weintraub said. “I think it’s the results that really matter.”
“No data supports this idea”
Samuel Klein is the director of the Center for Human Nutrition at Washington University School of Medicine in St. Louis. Earlier this month, he and other obesity researchers wrote on this subject for an article in JAMA and came to the same basic conclusion as above.
“We decided to carefully review the literature and found that there simply is no data to support the idea that weight loss with GLP-1 agonist treatment causes effects on muscle mass, or on fat-free mass, which lead to abnormalities in physical function.” Klein told Gizmodo over the phone.
Incretin medications might be riskier for our muscles in some ways. All of the data mentioned above relates to people using these drugs for type 2 diabetes or obesity, but their success has also driven public demand that has regularly exceeded available supply. This, combined with high list prices (over $1,000 per month) and low insurance coverage, has fueled a gray and black market for medications, making it relatively easy for anyone to get their hands on them, even if they don’t necessarily need them. So a person who is already quite thin and takes semaglutide could potentially become underweight or lose significant amounts of muscle, although Klein notes that he has yet to see any case reports of such a phenomenon. Again, the risks of any medication can outweigh the benefits when it is used by people for whom it is not intended.
Rolling Muscle Loss Concerns
The lack of data supporting massive muscle loss hasn’t stopped some pharmaceutical companies from trying to counter the problem. Several companies are test a combination of GLP-1 with drugs designed to gain muscle or prevent muscle loss. It’s certainly possible that these combinations could improve people’s health even more than taking a GLP-1 alone, especially for older adults who are already at higher risk of losing muscle as they age. But these trials also shouldn’t be taken as an admission by big pharmaceutical companies that we really have reason to worry, Klein says.
“It’s a treatment that looks for a problem,” he said. “I think the first step would be to demonstrate that weight loss with these drugs in a subset of people results in harm through excessive loss of muscle mass and decreased physical function. And until you demonstrate it, it’s not clear that preventing muscle loss will have therapeutic effects that are worth it.
Actions to maintain muscle health
If you’re still concerned about potential muscle loss from taking these medications or weight loss in other ways, here’s some encouraging news: We already know how to help you reduce or prevent it.
“I spend a lot of time in the clinic counseling patients on this, making sure they are achieving adequate protein intake, and then making sure we put effort into strength or resistance training “Weintraub said. “Because we know that (these two things) can really mitigate the loss of muscle mass that we might see with anti-obesity drugs.”
For their part, experts like Weintraub and Klein endorse continued research examining muscle (and bone) loss linked to taking these drugs more closely. But they are also unequivocal about the current state of the evidence.
“We just have to follow the data – it’s the yellow brick road – and not get attached to any particular point of view. But right now, to my knowledge, there is no data to support that this is a problem,” says Klein.