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 a persistent claim made about these drugs that would make any potential user wary: They don’t only help you lose weight—they supposedly hollow out your muscle mass at the same time, making you weak and vulnerable to all sorts of future health problems down the line. But what does the current science say, and just how worried should you be about muscle loss if taking these drugs?
Semaglutide (sold as Ozempic and Wegovy) and tirzepatide (sold as Mounjaro and Zepbound) are the most recent additions to a class of drugs known as incretins, which mimic hormones important to our metabolism and sense of hunger, among other functions. Semaglutide mimics GLP-1, while the newer tirzepatide mimics GLP-1 and another hormone, GIP. Both drugs have been found to help people safely, reliably, and substantially lose more weight on average than diet alone or other treatments, outside of bariatric surgery. Studies have also suggested that these medications can stave off heart, kidney, and liver disease in obese people vulnerable to it and possibly even help treat addiction and other conditions not strictly tied to obesity or diabetes.
As impressive as these drugs seem to be, no treatment comes without its potential negatives. Users will commonly experience gastrointestinal issues like vomiting and diarrhea, though these symptoms tend to wane over time. They may also cause rare but potentially serious complications like gastroparesis, often referred to as stomach paralysis.
Some critics have also alleged that GLP-1s can dangerously sap our muscle mass, but experts interviewed by Gizmodo say this claim isn’t currently backed by the data or our understanding of how these drugs work.
The skinny on muscle loss and GLP-1 use
For starters, the possibility of muscle loss while taking these drugs isn’t surprising. Long before Ozempic appeared on the scene, doctors have known that this can happen with any form of weight loss. When we slim down, we typically lose some combination of fat and fat-free mass, also known as lean body mass, which can include our muscles. And while there might be some other aspects of GLP-1s that help us lose weight, they primarily reduce our appetite and increase our sense of fullness, leading us to consume less calories over time. In other words, there’s nothing particularly novel about how we lose weight while taking them.
Studies have found that when people lose significant weight through diet alone or via bariatric surgery, 20% to 30% of that weight is lean body mass. And so far, we’re not finding that GLP-1 drugs are veering dramatically from this baseline. A 2024 review of clinical trial data on semaglutide, for instance, found that the proportion of lean body mass lost while losing weight ranged from 0% to 40%. And large clinical trials of tirzepatide have found that the percentage of lean body mass lost is in line with the percentage lost through diet or surgery.
“So it really is on par,” Michael Weintraub, an endocrinologist and clinical obesity researcher at New York University Langone Health, told Gizmodo over the phone. “And there’s no reason to think there’s some unique mechanism of these GLP-1 agonists that is causing a kind of specific muscle mass loss.”
These numbers alone don’t tell the full picture either. Even with the highest figures, obese people are still losing more fat than lean body mass and that’s undeniably a net positive, Weintraub says. One reason why muscle loss can be dangerous is that it can make us frail and less able to carry out our daily functions. But that’s absolutely not what the research is showing. Compared to placebo, people on these drugs have reported a better quality of life and improved physical functioning. Some limited data have also suggested that these drugs can cause a loss of lean body mass but without actually compromising the quality of our muscles.
“When I see my patients, they’ll say things like: ‘Well, I just feel so much better, I’m able to function so much better. I’m able to go up and down the subway without having to stop,’” Weintraub said. “Those are the outcomes, I think, that actually matter.”
‘No data to support the notion’
Samuel Klein is thedirector of the Center for Human Nutrition at Washington University School of Medicine in St. Louis. Earlier this month, he and other obesity researchers wrote about this very topic for an article in JAMA and came to the same basic conclusion as above.
“We decided to review the literature carefully and actually found that there is just no data to support the notion that weight loss with GLP-1 agonist therapy causes effects on muscle mass, or fat free mass, that lead to abnormalities in physical function,” Klein told Gizmodo over the phone.
There are some potential ways that incretin drugs could be riskier when it comes to our muscles. All the data mentioned above pertains to individuals using these medications for either type 2 diabetes or obesity, but their success has also driven a public demand that has regularly outmatched the available supply. That, combined with high list prices (upwards of $US1,000 a month) and low insurance coverage, has fueled a gray and black market for the drugs, making it relatively easy for anyone to get their hands on it, even if they don’t necessarily need it. So someone who’s already fairly thin and is taking semaglutide could possibly become underweight or lose relevant amounts of muscle, though Klein notes that he hasn’t seen any case reports of this happening yet. Then again, any drug’s risks can outweigh the benefits when used by people that it’s not meant for.
Riding muscle loss worries
The lack of data supporting massive muscle loss hasn’t stopped some drug companies from trying to counteract the issue. Several companies are testing a combination of GLP-1s with drugs designed to gain muscle or prevent muscle loss. It’s certainly possible that these combinations might improve people’s health even more than taking a GLP-1 alone, especially for older people who are already at higher risk of losing muscle as they age. But these trials shouldn’t be seen as an admission by Big Pharma that we really have something to worry about either, Klein argues.
“It’s a treatment looking for a problem,” he said. “I think the first step would be is to demonstrate that weight loss with these medications in a subset of people causes harm by excessive muscle mass loss and decreased physical function. And until you demonstrate that, it’s unclear that preventing the muscle loss will have therapeutic effects that are worth it.”
Actions to maintain muscle health
If you are still worried about potential muscle loss from taking these drugs or losing weight another way, then here’s some encouraging news: We already know how to help reduce or prevent it.
“I spend a lot of time in the clinic counseling patients on this, making sure that they’re attaining adequate protein intake, and then making sure that we’re spending effort on strength, or resistance, training,” Weintraub said. “Because we know that [those two things] can really mitigate the muscle mass loss that we might see with anti-obesity medications.”
For their part, experts like Weintraub and Klein do endorse further research looking more closely at muscle (and bone) loss while taking these drugs. But they’re also unequivocal about where the evidence stands for the time being.
“We just have to follow the data—it’s the yellow brick road—and not be wedded to any particular viewpoint. But right now, there are no data that I’m aware of supporting that this is a problem,” Klein says.
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