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Incretin-Based Obesity Medications Show Minimal Lean Muscle Mass Loss in 6-Month Prospective Study
Loss of lean muscle mass along with fat mass is a concerning side effect of the incretin-based antiobesity medications, making the new study results encouraging.
A new study found that individuals being treated with GLP-1 (glucagon-like peptide-1) receptor agonists or combined GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonist for weight loss experienced minimal loss of lean muscle mass during 6 months of treatment while achieving significant reductions in overall body weight and fat mass.
Close supervision by an obesity management specialist combined with regular resistance training and consistent protein intake were associated with better muscle retention and strength, study authors reported.
The prospective cohort study, to be presented at the European Congress on Obesity (ECO 2025) in Malaga, Spain, included 200 adults (99 men, 101 women, mean age 47 years) with overweight or obesity (BMI ≥25 kg/m²) and mean baseline weight of 31.4 kg/m². Participants received either the GLP-1 receptor agonist semaglutide (40%) or the GLP-1/GIP combination mimetic tirzepatide (60%). All participants were under the supervision of a board-certified obesity physician who provided education on medication use, resistance training, and protein intake.
After 6 months of treatment, the average weight of women decreased from 156 lbs (71 kg) to 137 lbs (62 kg), a reduction of 12%. The weight loss among men was similar, with an average decrease from 223 lbs ( 101 kg) to 193 lbs (to 88 kg), a 13% reduction. Reporting on the primary outcome, change in muscle and body fat mass, the investigators found that the composition of the weight loss was predominantly fat mass: women lost an average of 10.8 kg of fat mass and only 0.63 kg of muscle mass, while men lost 12 kg of fat mass and just 1 kg of muscle mass.
"This six-month study demonstrates that GLP-1 and dual GLP-1/GIP receptor agonists effectively reduce [both] weight and body fat mass in individuals with obesity," Dinabel Peralta-Reich, MD, assistant professor of pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell and colleagues said in a statement. “While some muscle loss is expected, the study suggests that, with close supervision by an expert obesity doctor, muscle loss can be minimized."
Peralta-Reich and team assessed body composition a baseline, 3 months, and at 6 months using bioelectrical impedance analysis with the InBody 570 system, which provides detailed measurements of muscle, fat, and water distribution. The researchers collected both quantitative data on body composition changes and qualitative information regarding medication adherence, physical activity, and nutrition.
Adherence to medication, based on participant self-report, began and remained high, at 95% at the 3-month mark and 89% after 6 months. Peralta-Reich et al identified several critical factors that appeared to contribute to the preservation of lean mass during weight loss, including "self-reported protein intake, medication adherence, and regular follow-up." They concluded that "these drugs help individuals lose body fat while preserving lean mass," though they emphasized that "further research is needed to better understand the roles of diet and exercise in preserving muscle mass."
The study is ongoing, with additional data being collected. Researchers are still analyzing the differences in weight loss, lean mass preservation, and fat mass reduction between participants using tirzepatide versus semaglutide.
These findings are particularly significant as concerns about muscle loss have been raised with incretin-based weight reduction therapies that promote rapid decreases in body mass.2 The preservation of lean muscle mass is critical for maintaining metabolic health, functional capacity, and reducing the risk of weight regain following successful obesity treatment.3
