Hardly a day goes by without hearing something new about the latest diabetes and obesity drugs, semaglutide and tirzepatide. Usually the response is positive, but there is one persistent claim about these drugs that would make any potential user suspicious: Not only do they help you lose weight, but they also supposedly weaken muscle mass at the same time, leaving you weak and vulnerable to all sorts of future health problems. But what does the current science say, and how concerned should you be about muscle loss when taking these drugs?
Semaglutide (sold as Ozempic and Wegovy) and Tirzepatide (sold as Mounjaro and Zepbound) are the Latest additions to a class of drugs known as incretins, which mimic hormones important for our metabolism and hunger, among other things. Semaglutide mimics GLP-1, while the newer tirzepatide mimics GLP-1 and another hormone, GIP. Both drugs have been found to help people lose weight safely, reliably, and on average, significantly more than diet alone or other treatmentsoutside of bariatric surgery. Studies have also shown that these drugs can prevent and possibly even help treat heart, kidney and liver disease in overweight people who are susceptible to it Seeks and other conditions not necessarily related to obesity or diabetes.
As impressive as these drugs seem to be, no treatment comes without potential downsides. Users often experience gastrointestinal problems such as vomiting and diarrhea, although these symptoms subside over time. They can also cause rare but potentially serious complications, such as Gastroparesisoften referred to as gastric paralysis.
Some critics also claim that GLP-1 can dangerously weaken our muscle mass. However, experts interviewed by Gizmodo say that this claim is currently not supported by data or our understanding of how these drugs work.
The most important thing about muscle wasting and GLP-1 use
First of all, the possibility of muscle loss when taking these drugs is not surprising. Long before Ozempic came along, doctors knew that this could happen with any form of weight loss. When we lose weight, we typically lose a combination of fat and fat-free mass, also known as lean body mass, which can include our muscles. And while GLP-1 may help us lose weight in other ways, they primarily reduce our appetite and increase our feelings of fullness, causing us to eat fewer calories over time. In other words, there is nothing particularly new about how we lose weight when taking these drugs.
Studies have shown that people who lose significant weight through diet or bariatric surgery alone 20% to 30% of this weight is lean body mass. And so far we have found no evidence that GLP-1 drugs dramatically deviate from this baseline. Review 2024 For example, clinical trial data on semaglutide found that the proportion of muscle mass lost during weight loss ranged from 0% to 40%. And large clinical trials on tirzepatide have found that the percentage of lean body mass lost is equal to the percentage lost through diet or surgery.
“So it’s really comparable,” Michael Weintraub, an endocrinologist and clinical obesity researcher at New York University 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 kind of specific muscle mass loss.”
But those numbers alone don’t tell the whole picture. Even at the highest numbers, obese people still lose more fat than muscle mass, and that’s undeniably a net gain, Weintraub says. One reason muscle loss can be dangerous is that it can make us frail and less able to perform our daily tasks. But that’s absolutely not what the research shows. Compared to placebos, people who took this Drugs have reported better quality of life and improved physical performance. Some limited data have also recommended that these drugs can cause a loss of muscle mass without actually affecting the quality of our muscles.
“When I see my patients, they say things like, ‘I just feel so much better, I can function so much better. I can ride the subway without having to stop,'” Weintraub said. “Those are the results that really matter, in my opinion.”
“No data to support this assumption”
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 topic for an article in JAMA and came to the same basic conclusion as above.
“We decided to carefully review the literature and actually concluded that there are simply no data to support the notion that weight loss from GLP-1 agonist therapy has effects on muscle mass or fat-free mass that lead to abnormalities in physical function,” Klein told Gizmodo by phone.
There are a few potential reasons why incretin drugs might be riskier for our muscles. All of the data above refers to people taking these drugs for either type 2 diabetes or obesity, but their success has also created a public demand that regularly exceeds the available supply. This, combined with high list prices (over $1,000 per month) and low insurance coverage, has created a Grey and black market for the drugs, making it relatively easy for anyone to get hold of them, even if they don’t necessarily need them. So someone who is already quite thin and takes semaglutide could potentially become underweight or lose significant amounts of muscle mass, although Klein notes that he hasn’t seen any case reports of this happening. On the other hand, the risks of any drug can outweigh the benefits when taken by people it’s not intended for.
Concerns about muscle atrophy while riding
The lack of data proving massive muscle loss has not stopped some pharmaceutical companies from trying to counteract the problem. Several companies are Testing a combination of GLP-1 with drugs designed to prevent muscle growth or muscle breakdown. It’s quite possible that these combinations could improve people’s health even more than taking GLP-1 alone, especially in older people who are already at higher risk of muscle loss as they age. But these studies shouldn’t be seen as an admission by the pharmaceutical industry that we really have to worry, Klein argues.
“It’s a treatment that looks for a problem,” he said. “I think the first step would be to prove that weight loss with these drugs is harmful in a subset of people through excessive muscle mass loss and reduced physical function. And until you can prove that, it’s unclear whether preventing muscle loss has therapeutic effects worth it.”
Measures to maintain muscle health
If you’re still worried about possible muscle loss from taking these medications or losing weight in other ways, we have good news for you: We already know how to reduce or prevent it.
“I spend a lot of time in the clinic counseling patients on this, making sure they are getting adequate protein intake, and then making sure we are focusing on strength or resistance training,” Weintraub said. “Because we know that [those two things] can really mitigate the loss of muscle mass that can occur with anti-obesity drugs.”
For their part, experts like Weintraub and Klein advocate further research that looks more closely at the muscle (and bone) loss that occurs when taking these drugs, but they are also clear about the current evidence.
“We just have to follow the data – that’s the yellow brick road – and not commit to a particular position. But at the moment I’m not aware of any data that shows that this is a problem,” says Klein.