New Research Explores GLP-1 Medications, Exercise, and Muscle Preservation
Physical Activity Patterns Among GLP-1 Users
"The findings challenge the assumption that weight loss naturally leads to increased physical activity."
— Study lead Sajana Maharjan, M.D.
A study presented at ENDO 2026 examined physical activity changes among adults with obesity who began taking GLP-1 receptor agonists. Researchers from HSHS St. John's Hospital analyzed data from the National Institutes of Health's All of Us Research Program, linking electronic health records with Fitbit activity data.
The retrospective pre-post cohort study included 1,950 adults with obesity who started a GLP-1 medication, of whom 753 had sufficient wearable-device data for analysis. The cohort was 78.6% female with a mean age of 52.7 years.
Results showed that average daily steps decreased from 5,047 to 4,487 steps per day after starting treatment. Average moderate-to-vigorous physical activity (MVPA) minutes fell from 28 to 22 minutes per day. The largest declines were observed in men and in individuals reporting joint or muscle pain. Age, heart failure, or prior stroke did not alter the results.
Exercise and GLP-1 Combination for Fitness Outcomes
Structured moderate-to-vigorous exercise was the primary contributor to improvements in physical fitness during long-term weight maintenance, even when weight loss was aided by GLP-1 RA therapy.
Study Design and Participants
This secondary analysis used data from a randomized, placebo-controlled clinical trial published in the journal Sports Medicine. It included adults aged 18 to 65 with obesity (BMI 32-43 kg/m²) without diabetes. Participants first underwent an 8-week, 800-kcal/day low-calorie diet. Those who achieved at least a 5% body weight reduction were then randomized.
Intervention Groups
Over 52 weeks, participants were allocated to one of four groups:
- Placebo with usual physical activity
- Placebo with structured exercise
- Liraglutide (a GLP-1 RA, 3.0 mg daily) with usual physical activity
- Liraglutide combined with structured exercise
The structured exercise program followed WHO recommendations, featuring supervised group interval cycling and circuit training, plus individual moderate-to-vigorous activity. Participants in exercise groups completed a median of 2.65 sessions per week.
Key Findings
A total of 193 participants were randomized, with approximately 85% completing the 52-week intervention.
Physical Function and Mobility: Improvements in physical functional performance were most evident in groups that included exercise. The combined exercise and liraglutide group completed stair-climb tests significantly faster than those receiving liraglutide alone or placebo. Liraglutide alone did not improve stair-climb performance despite sustained weight loss.
Cardiorespiratory Fitness: VO₂peak relative to fat-free mass increased by approximately 10% in the exercise and combined treatment groups. Liraglutide alone did not show a statistically significant improvement compared to placebo.
Muscle Strength: Maximal knee extensor torque remained stable across all groups. Strength relative to body weight improved in all active treatment groups due to weight reduction. Muscle quality declined in the placebo group but was maintained in those who exercised or received liraglutide.
Dose-Response Relationship: Each additional 10 minutes of weekly exercise was linked to faster stair-climb performance and higher VO₂peak relative to fat-free mass.
Apitegromab for Lean Mass Preservation
"GLP-1s have been associated with muscle mass and strength loss. The new medication may help reduce these effects."
— Prof Alexander Miras, Ulster University
A phase 2 randomized, double-blind, placebo-controlled trial published in Nature Medicine evaluated whether apitegromab, a monoclonal antibody targeting myostatin, can preserve lean body mass during weight loss induced by tirzepatide.
Study Details
The 24-week trial enrolled 102 adults with overweight or obesity. Participants were randomly divided into two groups: 51 received apitegromab plus tirzepatide, and 51 received placebo plus tirzepatide.
Results
Total weight loss was similar between groups. However, lean mass accounted for 14.6% of total weight loss in the apitegromab group versus 30.2% in the placebo group. The apitegromab group lost approximately 1.9 kg less lean mass compared to the placebo group. In absolute terms, the apitegromab group lost an average of 1.6 kg of lean mass, while the placebo group lost 3.5 kg.
No significant differences were observed between groups in grip strength, sit-to-stand tests, or insulin sensitivity. Side effects were similar between groups and mostly mild.
Expert Commentary
"Larger and longer trials are needed to check safety and whether the drug benefits health or function."
— Prof Naveed Sattar, University of Glasgow
Dr Brendan Gabriel (University of Aberdeen) noted that lean mass is a proxy for muscle mass and does not measure muscle directly. He observed that no significant differences in grip strength or sit-to-stand tests were found, possibly due to the short trial duration.
Dr Marie Spreckley (University of Cambridge) stated the findings are promising but from a phase 2 trial, and that larger and longer studies are needed to determine if these changes translate into meaningful health benefits.
Limitations
- The study was funded by apitegromab's producer, Scholar Rock
- Most participants were women
- The trial duration was 24 weeks
- The sample size was small
- The study excluded people with diabetes and significant cardiometabolic disease
- Physical activity was not objectively measured