This meteoric rise in prominence has invited enhanced scrutiny and skepticism. In January, the media was abuzz with stories about “Ozempic face,” a reported tendency for Ozempic users to lose healthy-looking fat from their faces, resulting in a saggy, aged appearance.
Now, people are asking a new question: Do Ozempic and other drugs like it cause unhealthy muscle loss?
Ozempic and the New Weight Loss Drugs
Ozempic is only the most famous of a new generation of diabetes drugs that is utterly changing the landscape of obesity medicine:
Ozempic (semaglutide), an injectable drug indicated for type 2 diabetes
Wegovy (semaglutide), essentially Ozempic marketed for weight loss
Rybelsus (semaglutide), an oral formulation of semaglutide
Mounjaro (tirzepatide), a related diabetes medication that causes even more dramatic weight loss
Semaglutide is a GLP-1 receptor agonist, one of a family of drugs that mimic the effect of a hormone that stimulates insulin secretion and prompts feelings of hunger. Tirzepatide is technically a dual GIP/GLP-1 receptor agonist — it acts as two hormones instead of just one — but it is generally thought of as a cousin of semaglutide.
Semaglutide and tirzepatide are almost certainly the two best weight loss medications ever developed. And weight loss, no matter how it’s achieved, always involves some loss of muscle and lean mass, in addition to the loss of fat. But there is now a rising concern that these drugs cause too much muscle loss.
Ozempic and Muscle Loss
Experts were already cautious about muscle loss before Ozempic became a celebrity among drugs. A 2021 meta-analysis by a team of Japanese doctors analyzed 18 randomized controlled trials of GLP-1 receptor agonists. The work showed that these medications create significant drops in “fat-free mass” and concluded that “it is important to pay attention to muscle loss.” Semaglutide had the strongest effect of all, though tirzepatide was not evaluated.
Recent interest in the issue was touched off by Peter Attia, MD. Dr. Attia, whose private practice is devoted to the science of longevity, has a large social media following. On a recent episode of his podcast, Attia discussed semaglutide and tirzepatide in detail.
In the podcast, Attia highlights what he calls a “massive flaw” in the work of the scientists and regulators validating these drugs as weight loss treatments: “They don’t care about body composition.” He goes on to explain that there has been very little attention paid to how much muscle these patients are losing in comparison to how much fat they’re losing. In Attia’s telling, an Ozempic user could lose 20 pounds of mostly lean mass — a profoundly unhealthy change in body composition — but scientists and the U.S. Food and Drug Administration (FDA) would still count it as a win for the drug.
The podcast followed an earlier blog post on the same topic, in which Attia warned that both physicians and patients should “exercise extreme caution” in the use of semaglutide and tirzepatide. Attia suggested that the drugs are wholly inappropriate for patients without excess fat and for those at any risk of sarcopenia (muscle loss); he encouraged anyone using the drugs to do everything in their power to counteract the potential losses in muscle and bone mass.
Attia is not alone — other doctors have sounded the same alarm. And a 2022 review in Obesity called on scientists to prioritize research and development of weight loss drugs that preserve lean mass in addition to suppressing appetite. The authors “suggest that the regulatory guidelines should be revisited to focus more on the quality of weight loss and its maintenance rather than the absolute weight loss.”
As yet, no study of semaglutide or tirzepatide has focused on body composition. We have a modicum of good data from larger studies that gave body composition scans to small subsets of volunteers.
In 2020, Diabetologia published a body composition analysis of 88 volunteers with type 2 diabetes who used semaglutide for one year. These participants lost an average of 12.5 pounds. Of that weight loss, there was a 7.5-pound reduction in fat mass and a 5-pound reduction in lean mass.
In 2021, a major trial of semaglutide’s weight loss potency examined the body composition of a minority of participants. These patients did not have diabetes, and they took a much larger dose of the drug. The 95 participants to undergo a body scan lost an average of 18 pounds of fat — and 12 pounds of lean mass.
The sample is not huge, with fewer than 200 patients overall, but the two trials agreed: Semaglutide users lost about 40 percent lean mass and 60 percent fat.
How does that compare with people losing weight by other means? In most overweight adults, “fat-free mass contributes only ∼20–30 percent to total weight loss,” according to a 2017 review. If this generalization is accurate, it suggests that semaglutide may be causing an undue amount of muscle loss, as much as double the expectation.
One study has also analyzed the body composition of a very small sample of tirzepatide users. Nine volunteers using the highest dose of tirzepatide (15 milligrams) lost an average of five pounds of lean mass, and 14.6 pounds of fat mass, a ratio much more in line with expectations for diet-induced weight loss. Volunteers on lower doses had similar ratios of lean-to-fat mass loss.
In an earlier Instagram reel, Attia detailed his personal experience prescribing the drug to his patients:
“I’ll tell you what’s wrong with it. Almost without exception, every patient we’ve put on this drug has lost muscle mass. And they’ve lost it at a rate that alarms me.”
At least one other doctor has had a similar experience. Florence Comite, MD, an endocrinologist and the founder of New York City’s Comite Center for Precision Medicine & Health, told the Daily Mail that “what we see here at the center, it is usually more muscle loss than fat.” Dr. Comite believes that her patients on semaglutide typically lose about 60 percent lean mass and only 40 percent body fat, reversing the ratio from the trials discussed above.
It’s worth noting that Attia and Comite are generally not treating average people with diabetes; they each operate clinics for affluent patients that are highly motivated to optimize their health. It is possible that their experiences, even if accurate, are not representative of the vast majority of people who are prescribed these drugs.
Is There a Reason to Worry?
Weight loss, no matter how it’s achieved, almost invariably involves the loss of both fat and muscle.
This isn’t usually considered a problem. The typically modest amount of lean mass loss that accompanies weight loss is believed to be healthy and natural, “consistent with the new, reduced body weight rather than a diet-induced ‘muscle deficit.’”
If semaglutide and tirzepatide are causing excessive muscle loss, though, it could be problematic for users. Muscle mass, physical function, and strength are increasingly important as we age, part of the reason that strength training is recommended even for older adults.
Lean muscle is also especially important for people with diabetes. The muscles, more than any other part of the body, are responsible for removing glucose from the bloodstream, and muscle loss will likely lead to higher blood sugar numbers and further metabolic impairment. Sarcopenia — age-related muscle loss — is both a cause and a consequence of diabetes.
But not all experts are concerned. MedPage Today recently released a special report on Ozempic and muscle loss. Reporter Kristina Fiore spoke to two endocrinologists with experience prescribing the drug.
Karl Nadolsky, DO, is an endocrinologist at Spectrum Health in Grand Rapids, Michigan, and an assistant professor of medicine at Michigan State University. Dr. Nadolsky emphasized that the trials suggesting the scale of lean mass loss also showed that users enjoyed convincing metabolic improvements: “The benefits outweigh the risks in people who have obesity or are overweight, especially when it’s complicated by cardiovascular disease, sleep apnea, and other conditions.”
Amy Rothberg, MD, a clinical professor of internal medicine in the Division of Metabolism, Endocrinology, and Diabetes at the University of Michigan, joined Nadolsky in recommending that the new weight loss drugs should be recommended only to people with a true need to lose weight, and that users should do what they can to help preserve muscle during weight loss.
How to Preserve Muscle on the New Weight Loss Drugs
There is a strong consensus in the medical community regarding the best ways to preserve lean (muscle) mass during weight loss:
Many different studies have found that resistance or strength-building exercise helps prevent muscle loss during weight loss, including in older and overweight people. The effect of cardiovascular exercise on muscle retention, on the other hand, “is less clear” — some studies show beneficial effects for cardio and low-intensity exercises like walking, but others do not.
The recommendation here is clear: Start resistance training. It may be the best way to retain healthy muscle mass while you’re losing weight.
How much protein should you be eating each day? The Mayo Clinic recommends that the average adult eat 0.8 grams (g) of protein per kilogram of body weight, but the requirements only go up for people over the age of 40 and for those regularly exercising. A 2015 article in the American Journal of Clinical Nutrition suggested a high-protein diet of 1.2 to 1.6 g of protein per kilogram of body weight for weight loss efforts.
For a 200-pound adult, that’s about 125 g of protein per day — the amount of protein in 21 eggs or nearly a pound of boneless, skinless chicken breast. This may seem like a huge amount of protein to eat, especially if you’re using one of these powerful weight loss drugs, which not only suppress appetite but also frequently have gastrointestinal side effects.
In effect, these guidelines ask most people to eat more protein even while they’re eating less food overall. This can be especially difficult due to protein’s demonstrated ability to curb the appetite. To hit this recommended daily minimum, you might have to make lean protein sources like seafood and chicken breast the focus of most of your meals.
(If you have kidney issues or any other conditions that limit your optimal protein intake, please ask your medical team for guidance.)
Several prominent doctors have warned that semaglutide (Ozempic) and other related drugs, initially developed for diabetes but widely used for weight loss, cause an unhealthy amount of muscle loss.
The data is meager, but it does suggest that Ozempic users might lose more lean muscle mass than normally expected from diet-induced weight loss. More study is necessary to be sure.
Even if Ozempic does have this unfortunate side effect, the benefits probably outweigh the risks for people with diabetes or a serious need to lose weight.
Regardless, doctors recommend resistance training and strength-building exercises to help preserve muscle mass during weight loss; Ozempic users would likely be wise to take up this healthy habit. Emphasizing dietary protein may also help prevent muscle loss.