Study suggests lean muscle mass loss can be minimized during weight loss therapy using newer incretin obesity drugs

New research to be presented at this year’s European Congress on Obesity (ECO 2025, Malaga, Spain, 11-14 May) shows that patients using GLP-1 or combined GLP-1 / GIP receptor agonist therapy for weight loss experienced minimal lean muscle mass loss as they lost weight across 6 months of treatment. The study is by Dr Dinabel Peralta-Reich, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell; Lenox Hill Hospital, Northwell Health, New York City, NY, USA, and Dr Alexandra Filingeri, New York Weight Wellness Medicine, New York City, NY, USA, and colleagues.

GLP-1 (glucagon-like peptide-1) receptor agonists, that include semaglutide and liraglutide and were initially used for type 2 diabetes, have also proven effective in managing obesity and promoting weight loss. More recently, tirzepatide, which combines GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), has also been granted approval to treat type 2 diabetes and / or obesity. As research continues to support the use of these medications, monitoring body composition, particularly muscle mass and atrophy, remains clinically significant. Obesity medicine specialists play a key role in designing interventions that promote weight loss while preserving lean mass.

This six-month prospective cohort study enrolled 200 adults (ages 18-65, BMI 25 kg/m² or above, with overweight or obesity) who were prescribed either the GLP-1 receptor semaglutide or the GLP-1 / GIP dual agonist tirzepatide, with 60% of participants (n = 120) receiving tirzepatide and 40% (n = 80) receiving semaglutide. Participants received education on using the medications, resistance training, and protein intake from a board-certified obesity physician.

Body composition was assessed at baseline, three months, and six months using bioelectrical impedance, using a system called the InBody 570. The InBody 570 is a professional body composition analyser that provides a detailed breakdown of muscle, fat, and water distribution using multi-frequency bioelectrical impedance analysis (BIA). It measures total body water (intracellular/extracellular), skeletal muscle mass, body fat percentage, visceral fat, and segmental muscle distribution.

Primary outcomes included changes in body fat and muscle mass, with data analysed using statistical modelling. Qualitative data on medication adherence, physical activity, and nutrition were also collected. Participants served as their own controls for pre- and post-intervention comparisons.

All 200 participants (99 males, 101 females) completed the study. The mean age was 47 years, with a mean baseline BMI of 31.4 kg/m² (but all over 25, all living with either overweight or obesity). At six months the average weight of women decreased from 156 pounds (71kg) to 137 pounds (62kg) – a loss of 12%; while the average weight of men decreased from 223 pounds (101kg) to 193 pounds (88kg) – a loss of 13%.

At six months, women had lost an average of 10.8kg of fat mass, but only 1.4 pounds of muscle mass (0.63kg), while men had lost 25 pounds of fat mass (12kg) and only 2.4 pounds of muscle mass (1kg).  

Medication adherence was 95% at three months and 89% at six months, based on self-reports. Qualitative data indicated that regular resistance training and consistent protein intake were associated with better muscle retention and strength. The study remains ongoing and more data continues to be collected. The differences between weight / lean mass / fat mass lost for tirzepatide and semaglutide are still being analysed.

The authors say: “This six-month study demonstrates that GLP-1 and dual GLP-1 / GIP receptor agonists effectively reduce weight and body fat mass in individuals with obesity. While some muscle loss is expected, the study suggests that, with close supervision by an expert obesity doctor, muscle loss can be minimised. Factors such as self-reported protein intake, medication adherence, and regular follow-up contributed to success. The data show that these drugs help individuals lose body fat while preserving lean mass. Further research is needed to better understand the roles of diet and exercise in preserving muscle mass.”