From the Guidelines
GLP-1 receptor agonists like liraglutide are not currently recommended for muscle preservation, as their primary indications are for type 2 diabetes management and weight loss in obesity. While weight loss from GLP-1 agonists appears to predominantly target fat mass rather than lean muscle mass, they are not specifically indicated for muscle preservation. Some preliminary research suggests GLP-1 agonists might have neutral or potentially beneficial effects on muscle compared to other weight loss methods, but this is not their primary function. The mechanism behind this potential muscle-sparing effect may involve GLP-1 receptors in muscle tissue affecting protein metabolism, as noted in various studies 1. However, for muscle preservation, established approaches remain more appropriate, including:
- Resistance training
- Adequate protein intake (1.2-2.0 g/kg/day)
- Sufficient caloric intake If you're concerned about muscle preservation during weight loss, combining these traditional approaches with medical supervision would be more appropriate than using GLP-1 agonists solely for this purpose. It's also worth noting that recent guidelines, such as the 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline, focus on the use of GLP-1 agonists for reducing the risk of major adverse cardiovascular events (MACE) in patients with peripheral artery disease and type 2 diabetes, rather than muscle preservation 1.
From the Research
GLP-1 Receptor Agonists and Muscle Preservation
- GLP-1 receptor agonists, such as liraglutide, have been shown to induce weight loss, which may result from the loss of both fat and skeletal muscle 2, 3.
- However, the effects of GLP-1-based therapies on lean mass changes in clinical trials are heterogeneous, with some studies reporting reductions in lean mass ranging from 40% to 60% of total weight lost, while others show lean mass reductions of approximately 15% or less of total weight lost 2.
- Changes in lean mass may not always reflect changes in muscle mass, as lean mass includes not only muscle but also organs, bone, fluids, and water in fat tissue 2.
- Contemporary evidence suggests that skeletal muscle changes with GLP-1RA treatments appear to be adaptive, with reductions in muscle volume commensurate with what is expected given ageing, disease status, and weight loss achieved 2.
- The improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function 2.
Factors Influencing Muscle Preservation
- Factors such as older age and severity of disease may influence the selection of appropriate candidates for GLP-1RA therapies due to the risk of sarcopenia 2.
- To further improve muscle health during weight loss, several pharmacological treatments to maintain or improve muscle mass are being developed in combination with GLP-1-based therapies 2.
- Future research on GLP-1-based and other therapies designed for weight loss should focus on more accurate and meaningful assessments of muscle mass, composition, as well as function, mobility, or strength, to better define their impact on muscle health 2.
Clinical Trials and Studies
- A meta-analysis of 19 randomized controlled trials found that GLP-1 receptor-based agonist treatment resulted in substantial reductions in fat body mass, with decreases in areas of both subcutaneous fat and visceral fat 3.
- Another study found that GLP-1 receptor agonists probably reduced the risk of all-cause death, but may have little or no effect on cardiovascular death in people with chronic kidney disease and diabetes 4.
- Dual GIP/GLP-1 receptor agonists, such as tirzepatide, have shown better dose-dependent efficacy in reducing HbA1c and body weight compared to placebo, basal insulin, or GLP-1 analogues 5.