Weight loss with GLP-1 medicines does not result in a disproportionate loss of muscle mass or function in obese mice and humans.

GLP-1 medicines predominantly reduce body fat in obese mice, with a small but significant decrease in lean body mass (LBM).

• Four pre-clinical studies and a proof-of-concept clinical trial were conducted to address concerns about lean body mass and skeletal muscle loss.
• The reduction in body weight with GLP-1 medicines was disproportionately composed of fat mass rather than lean tissue.
• Among lean tissues, loss of liver mass exceeded the change in muscle mass.
• The study used obese mouse models across multiple pre-clinical experiments.

While absolute muscle mass and strength decreased in obese mice treated with GLP-1 medicines, relative muscle mass and strength improved.

• Absolute muscle mass and strength decreased with GLP-1 medicine treatment.
• Relative muscle mass and strength improved following GLP-1 treatment.
• The improvement in relative muscle parameters resulted in better running performance.
• These findings were observed in middle-aged obese mice.

GLP-1 medicines have a distinct effect on the muscle proteome compared to calorie restriction.

• Muscle atrophy during immobilization was similar between GLP-1 medicine-treated and control conditions.
• The muscle proteome differed between GLP-1 medicine treatment and calorie restriction, suggesting mechanistically distinct effects on muscle tissue.
• This finding was derived from pre-clinical studies in mice.
• The distinct proteomic signature suggests GLP-1 medicines do not simply mimic calorie restriction at the muscle molecular level.

Patients with obesity on GLP-1 medicines improved their body composition without negatively affecting strength in a proof-of-concept clinical trial.

• The clinical trial is registered on clinicaltrials.gov (NCT05606471).
• Patients with obesity were the study population in the clinical component.
• Body composition improved in patients on GLP-1 medicines.
• Muscle strength was not negatively affected in the clinical patient population.
• The trial was described as a proof-of-concept study.

In middle-aged mice and men, GLP-1 medicines slightly decrease absolute muscle values but positively impact body composition and mobility.

• The study specifically examined middle-aged subjects in both mouse and human components.
• Absolute muscle values showed a slight decrease with GLP-1 medicine use.
• Body composition outcomes were positive overall.
• Mobility was positively impacted, consistent with the improved running performance seen in mice.
• The findings address concerns raised by the large decrease in body weight associated with GLP-1 medicines.