Can we stop muscle loss when taking weight loss drugs?

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GLP-1 receptor agonists - such as Wegovy, Ozempic and Mounjaro - are now widely used for weight loss, but past research suggests they come with a cost: muscle loss. Now, international researchers say taking the drug apitegromab could help preserve our lean body mass during weight loss with tirzepatide (Mounjaro), in a study funded by the producers of the drug. To work this out, the researchers gave 102 people with overweight or obesity either tirzepatide plus apitegromab or tirzepatide plus an inactive placebo for 24 weeks. The team says that, while the weight loss between the groups was similar, the people who received apitegromab lost 1.9 kg less lean mass than those who received the placebo, which would represent them holding on to 54.9% more lean muscle mass. Additionally, the researchers say the drug combination was well-tolerated and could be used in the future to help people retain their important muscle mass.

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From: Springer Nature

Protecting muscle during weight-loss treatment

A drug called apitegromab may help to preserve lean body mass during weight loss with tirzepatide, a GLP-1 receptor agonist, according to a phase 2 clinical trial published in Nature Medicine. The findings suggest that blocking a protein that limits muscle growth may improve patient weight loss outcomes by reducing the loss of lean body mass.

GLP-1 receptor agonists such as tirzepatide can help people lose a substantial amount of body weight. However, some of this weight loss can come from lean body mass. Lean body mass is made up mostly of skeletal muscle, which is important for strength, general health, metabolism, and physical activity. Apitegromab is a drug designed to block myostatin, a protein involved in the breakdown of skeletal muscle.

Richard Pratley and colleagues tested apitegromab in a randomised, double-blind, placebo-controlled phase 2 trial. The trial included 102 adults with overweight or obesity, who received either tirzepatide plus apitegromab or tirzepatide plus a placebo for 24 weeks. By the end of the study, total weight loss was similar between the two groups, but people who had received apitegromab lost 1.9 kg less lean mass than those who received the placebo, which represents a 54.9% greater retention of lean mass. Lean mass made up 14.6% of total weight loss in the apitegromab group, compared with 30.2% in the placebo group. Apitegromab was generally well tolerated, with similar rates of adverse events between the treatment groups including 39% of apitegromab subjects experiencing any adverse event, compared to 36% in the placebo group.

The authors suggest that apitegromab may help to preserve lean mass during tirzepatide treatment and could help to improve the composition of weight loss. However, they note that the trial was relatively small, included more than 80% female participants, and excluded people with significant cardiometabolic conditions, including diabetes.

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Nature Medicine
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Organisation/s: AdventHealth Translational Research Institute, USA
Funder: This work was supported by Scholar Rock, Inc.
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