Research
Hormonal
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.
If you are on semaglutide and worried about muscle loss, ask your doctor if tirzepatide (a dual GLP-1/GIP drug) might be a better option for you, as it appears to spare more muscle. Newer triple-agonist drugs are also in development.
ModerateQualifiesMEDIUM confidence
Of interest is that the proportion of lean loss with semaglutide was greater than that of tirzepatide, despite tirzepatide producing greater overall weight loss. ... The potential for bone and muscle sparing aspects of GlP- 1/GIP dual agonism needs to be explored.
Why this rating
Based on comparative substudy data (semaglutide vs tirzepatide) and animal studies, but human body composition data for newer triple agonists is not yet published.
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
narrative_reviewCited 22×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- 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.Good
- 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
Related findings · Hormonal
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- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
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