AIMS: To compare lean mass changes between incretin-based therapies (GLP-1 receptor agonists and dual GLP-1/GIP agonists) and intensive lifestyle interventions in adults with overweight or obesity, and to determine whether the proportion of total weight lost as lean mass differs between these treatment modalities.
MATERIALS AND METHODS: PubMed, Embase, Cochrane CENTRAL, and Web of Science were searched from inception through 20 January 2026. Randomised controlled trials of semaglutide, tirzepatide, liraglutide or lifestyle interventions reporting body composition outcomes measured by dual-energy X-ray absorptiometry or magnetic resonance imaging were included. The co-primary outcomes were the absolute change in lean mass (kg) and the proportion of total weight loss attributable to lean mass. Data were pooled using random-effects models. Risk of bias was assessed using Cochrane RoB 2, and certainty of evidence was evaluated using GRADE.
RESULTS: Twenty randomised controlled trials (RCTs) comprising 15 782 participants met inclusion criteria. Lean mass constituted 25%-39% of total weight lost with incretin agonists: semaglutide (35.2% [95% CI: 31.5-38.9]), tirzepatide (25.4% [22.8-28.0]) and liraglutide (26.8% [23.1-30.5]). Lifestyle interventions showed comparable proportional lean mass loss (26.2% [24.1-28.3]; p = 0.42 for comparison), while lifestyle plus resistance training demonstrated the most favourable profile (17.5% [14.2-20.8]). Heterogeneity was moderate (I2 = 68%). No publication bias was detected (Egger's test p = 0.23).
CONCLUSIONS: Lean mass loss during significant weight reduction is substantial, and the proportion of weight lost as lean mass is broadly comparable between incretin-based pharmacotherapy and lifestyle interventions. Muscle mass can be significantly preserved by integrating resistance training, adequate protein intake, and body composition monitoring into weight-loss treatment programs.
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Endocrine |  |
| Public Health | Coming Soon... |
| Special Interest - Obesity -- Physician | Coming Soon... |
A good reminder that lean body mass decreases with weight loss, whether by lifestyle measures or incretin therapy.
Many practitioners likely know about the impact of GLP1s on lean mass, but it is still helpful to have this systematic review to document the extent and the potential role of interventions to reduce muscle loss.
The effect on lean mass loss with incretin-based therapy for weight loss has been incorporated into clinicians' discussion with patients when using these agents. This review brings home the message that lean mass loss also occurs with lifestyle interventions to a comparable extent to GLP-1 agents. So, clinicians should likewise incorporate into discussions with patients using lifestyle interventions the importance of resistance training, adequate protein intake, and body composition monitoring.
These findings are important because they help to counter the perception that weight loss from GLP-1 results in more lean body mass loss than other approaches. The study also highlights the importance of resistance exercise in minimizing this problem. Counselling on resistance exercise should be a standard part of weight loss counselling, with or without the use of GLP-1 therapies.