In recent months, consumers have voiced concerns about potential side effects of semaglutide, a popular weight loss drug. Now, reports of muscle loss in many patients have heightened concern for some — but many experts argue that the "benefits outweigh the risks" for certain patients.
In recent months, new weight-loss drugs, which were originally developed as diabetes medications, have been growing in popularity. These medications include Novo Nordisk's semaglutide, branded as Ozempic for diabetes and Wegovy for obesity, and can help people control their appetite and food intake.
Following reports of "Ozempic face," a result of rapid weight loss that makes the face look deflated and appear older, consumers and experts started raising concerns about another potential side effect — unintended muscle loss.
In an Instagram post, Peter Attia, a physician who focuses on the science of longevity, claimed that "almost every patient we put on this drug [semaglutide] has lost muscle mass at a rate that alarms me."
Attia said he believes FDA does not account for the type of weight that patients lost in the studies on the drug, ignoring whether it was muscle mass or fat loss.
"So all of the studies that we've talked about, the FDA has forced the primary outcome to be weight loss," Attia said. "They don't care about body composition."
According to a spokesperson for Novo Nordisk, the company "did not specifically study the medicine's impact on muscle mass" in its clinical trials.
While the manufacturer acknowledged that patients have lost muscle, it also reported that the patients studied had an overall higher proportion of muscle compared to their amount of fat.
"With regards to arm or leg weakness, this is not a listed adverse reaction in our US full prescribing information. We recommend that any patients experiencing side effects while taking Wegovy contact their healthcare provider," the company's statement said.
Endocrinologists and obesity medicine specialists said that while muscle mass loss can be a side effect of semaglutide, it is not unique to the drug or the GLP-1 agonist drug class.
"Muscle mass loss is part-and-parcel to losing weight," said Amy Rothberg of the University of Michigan, 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, an endocrinologist and obesity medicine specialist at Holland Hospital, noted that "all weight-loss interventions result in some lean mass loss." According to Nadolsky, lean mass loss involves both muscle loss and things like fluid loss.
Nadolsky highlighted subgroup data from the STEP 1 Study — semaglutide's primary clinical trial — which looked at 95 people who were on the drug and 45 people who received a placebo. The researchers conducted scans on all participants to monitor their body mass.
Participants who received the drug lost an average of 10.4% of their fat mass and 6.9% of their lean body mass, and participants who received a placebo lost an average of 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 said. While the data indicate that the drug caused lean mass loss, "the percentage of fat mass loss to lean mass loss is favorable."
According to Rothberg, people generally lose fat mass to lean mass at a ratio of 2:1. While this varies by age, gender, and physical conditioning, Rothberg noted that the STEP 1 data appear to fall within those parameters.
Still, Nadolsky said physicians overseeing any weight loss intervention should try 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."
That includes encouraging resistance training in patients participating in a weight loss program. A focus on muscle building is crucial for patients who are trying to lose weight, Nadolsky said.
Nadolsky also noted that trials have identified additional benefits even with the lean mass loss seen with semaglutide, including 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," Nadolsky said. "We shouldn't be scaring away people who have obesity and obesity-related complications. … The benefits outweigh the risks in people who have obesity or overweight, especially when it's complicated by cardiovascular disease, sleep apnea, and other conditions." (Fiore, MedPage Today, 3/16; Herz, New York Post, 3/14)
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