Does Wegovy Shrink Muscle Mass?

While “Ozempic face” may still dominate headlines around the potential side effects of semaglutide (Wegovy, Ozempic) and other popular new weight-loss drugs, social media has started to raise questions about whether losing muscle mass is yet another complication.

One physician claimed in an Instagram post that “almost every patient we put on this drug [semaglutide] has lost muscle mass at a rate that alarms me.”

But endocrinologists and obesity medicine specialists interviewed by MedPage Today said that while muscle mass loss can occur, it’s not unique to or more dramatic with semaglutide or its GLP-1 agonist drug class more broadly.

“Muscle mass loss is part-and-parcel to losing weight,” said Amy Rothberg, MD, of the University of Michigan in Ann Arbor, who is also a spokesperson for the Endocrine Society. “So in the context that semaglutide helps people lose weight, they are going to lose muscle mass.”

“But you lose muscle mass irrespective of the modality, whether that’s diet and exercise, bariatric surgery, or medications,” she said.

Karl Nadolsky, DO, an endocrinologist and obesity medicine specialist at Holland Hospital in Michigan, echoed that “all weight-loss interventions result in some lean mass loss.” Lean mass loss includes muscle loss but also includes things like fluid loss, Nadolsky said.

He pointed to subgroup data from the main clinical trial of semaglutide, the STEP 1 Study, looking at 95 people who were on the drug and 45 people who were taking placebo, all of whom had scans to monitor their body mass.

On average, those on the drug lost 10.4% of their fat mass and 6.9% of their lean body mass, while those on placebo lost 1.2% of their fat mass and 1.5% of their lean body mass.

“The placebo group lost almost 50% more lean mass than fat mass,” Nadolsky noted. While the data show that there is indeed lean mass loss with the drug, “the percentage of fat mass loss to lean mass loss is favorable.”

Rothberg noted that the study wasn’t powered to assess this outcome, but she said very generally speaking that with weight loss, people lose fat mass to lean mass at a ratio of 2:1. This certainly varies by age, gender, and physical conditioning, she said, but the STEP 1 data appear to fall within those parameters.

Nadolsky said with any weight loss intervention, physicians should aim to minimize muscle mass loss as much as possible, “as it’s beneficial for metabolic health and prevention or treatment of comorbidities, including type 2 diabetes,” he said.

That means encouraging resistance training in anyone who is working to lose weight, he said. It’s critical to have patients who are trying to lose weight also focus on building muscle, he said.

Semaglutide and newer weight-loss drugs should also be reserved for people who truly have obesity and overweight — not just anyone who wants to lose a few pounds, Rothberg and Nadolsky said.

“Some people just want to lose a little weight, but we shouldn’t give it to people who don’t need it,” Nadolsky said. “The risks outweigh the benefits in people who have obesity or overweight, especially when it’s complicated by cardiovascular disease, sleep apnea, and other conditions.”

Nadolsky noted that even with the lean mass loss seen with weight loss from semaglutide, trials have shown other benefits such as improvements in blood pressure, lipids, and glycemic control.

“All of those parameters improve with the weight loss, regardless of how much lean mass they lost,” he said. “We shouldn’t be scaring away people who have obesity and obesity-related complications.”

Please enable JavaScript to view the comments powered by Disqus.