Macro partitioning
GLP-1 receptor agonists (semaglutide) and dual GLP-1/GIP agonists (tirzepatide) cause significant lean mass loss during weight loss, with semaglutide losing approximately 45% of total weight as lean mass and tirzepatide losing 25.7%, posing a specific risk of frailty and fractures in older populations.
If you are taking semaglutide or tirzepatide, be aware that a significant portion of your weight loss (up to 45% for semaglutide) comes from lean mass, not just fat. This is especially risky if you are over 60. Discuss strategies to preserve muscle, such as resistance training or potentially newer combination therapies, with your provider.
Of weight lost with semaglutide, approximately 45% is from lean mass, while with tirzepatide, it is 25%. ... Of the total weight loss with semaglutide approximately 45% was lean mass and for tirzepatide it was 25.7%.
Why this rating
Based on Phase 3 substudies (STEP 1, SURMOUNT 1) using DEXA scans, though the paper notes these are not definitive for bone/muscle separation.
Source
New drugs for the treatment of obesity: do we need approaches to preserve muscle mass?
Donna H. Ryan · Reviews in Endocrine and Metabolic Disorders · 2025
DOI 10.1007/s11154-025-09967-4
More from this paper
- Myostatin-activin pathway inhibitors (MAPi), specifically bimagrumab, can reduce fat mass while preserving or increasing lean mass, offering a potential solution to the lean mass loss associated with GLP-1 agonists.Moderate
- Combining GLP-1 receptor agonists with other Nutrient Stimulated Hormones (NuSH) like glucagon or amylin, or using dual/triple agonists like tirzepatide, may result in less lean mass loss compared to single-agonist GLP-1 treatments.Moderate
Related findings · Macro partitioning
- Total daily protein intake of 1.6 g/kg/day is sufficient for maximizing resistance training-induced muscle gains, with an upper confidence interval of 2.2 g/kg/day.Strong
- Resistance exercise training combined with sufficient dietary protein intake acts synergistically to maximize skeletal muscle hypertrophy, with protein intake saturating around 1.6 g/kg/day for general populations and potentially requiring 2.0-2.2 g/kg/day for resistance-trained individuals.Strong
- Trans fats should be completely eliminated from the diet, as they increase LDL cholesterol, decrease HDL cholesterol, and are directly associated with increased coronary risk.Strong
This is one finding among thousands. Every one is graded and traced to its source, so you can see what the evidence actually supports. Browse the research →