What supplements help reduce muscle loss in patients taking Glucagon-like peptide-1 (GLP-1) receptor agonists?

Protein Supplementation and Resistance Training Are Essential to Mitigate Muscle Loss with GLP-1 Therapy

The most effective strategy to reduce muscle loss during GLP-1 receptor agonist therapy is combining high protein intake (targeting 1.2-1.6 g/kg/day or higher) with regular resistance training, as these interventions directly counteract the 15-40% of total weight loss that comes from lean body mass. 1, 2

Understanding the Muscle Loss Problem

GLP-1 receptor agonists cause substantial weight loss—up to 14.9% with semaglutide and 15-20.9% with tirzepatide—but a significant portion of this weight loss comes from fat-free mass (FFM). 3 Studies demonstrate that 15-40% of total weight lost can be FFM, which includes skeletal muscle, organs, bone, and fluids. 1, 2, 4 However, it's critical to understand that FFM is not synonymous with skeletal muscle mass alone—FFM includes non-muscle components, so actual skeletal muscle loss may be less dramatic than FFM numbers suggest. 1, 5

Primary Interventions: Protein and Resistance Training

High Protein Intake

• Target protein intake of 1.2-1.6 g/kg body weight per day or higher to preserve muscle mass during GLP-1-induced weight loss. 1, 2
• Adequate protein intake is one of the two fundamental countermeasures against muscle loss during pharmacological weight loss. 5
• A high protein diet should be instituted as part of a targeted and individualized nutrition regimen for each patient on GLP-1 therapy. 2

Resistance Training

• Perform frequent resistance training sessions (specific frequency not defined in guidelines, but regular/consistent training is emphasized). 1, 2
• Resistance exercise training is the other fundamental countermeasure alongside protein intake. 5
• The combination of resistance training and adequate protein can mitigate muscle loss, though evidence for efficacy specifically in the context of GLP-1 therapy is mixed. 1

Supplemental Nutritional Strategies

If protein and resistance training are insufficient to prevent muscle loss, consider adding specific nutrients:

• Branched-chain amino acids (BCAAs) may be beneficial for muscle preservation. 1
• Leucine (a specific BCAA) shows potential benefit. 1
• Creatine supplementation may help maintain muscle mass. 1
• Omega-3 fatty acids could support muscle health. 1
• Vitamin D may be beneficial, particularly given its role in muscle function. 1

Emerging Pharmacological Approaches

For patients at highest risk or with inadequate response to lifestyle interventions, newer pharmacological treatments are under development:

• Bimagrumab (a human monoclonal antibody that binds activin type II receptor) shows promise in preserving muscle mass while promoting fat loss. 1
• Other activin or myostatin inhibitors are being developed for combination with GLP-1 therapies. 1, 4, 6

High-Risk Populations Requiring Aggressive Intervention

Certain patient populations are at particularly high risk for accelerated sarcopenia and require more intensive muscle preservation strategies:

• Older adults (age-related sarcopenia risk). 2, 4, 6
• Patients with chronic kidney disease. 2
• Patients with liver disease. 2
• Patients with inflammatory bowel disease. 2
• Patients with prefrailty or existing sarcopenia. 6

For these populations, the combination of high protein intake and resistance training is not optional—it's essential to prevent adverse outcomes. 2

Important Clinical Context

The muscle changes with GLP-1 therapy may be largely adaptive rather than maladaptive. Recent magnetic resonance imaging studies suggest that reductions in muscle volume are commensurate with what is expected given aging, disease status, and weight loss achieved. 4, 6 Additionally, improvements in insulin sensitivity and reductions in muscle fat infiltration likely contribute to improved muscle quality, potentially lowering the probability for loss in strength and function. 4, 6

However, this adaptive response doesn't eliminate the need for intervention—it simply means the muscle loss isn't necessarily pathological, but prevention strategies are still warranted, especially in high-risk groups. 6

Common Pitfalls to Avoid

• Don't assume FFM loss equals skeletal muscle loss. FFM includes organs, bone, fluids, and water in fat tissue—actual skeletal muscle changes may be less severe than FFM numbers suggest. 1, 5
• Don't delay intervention. Start protein supplementation and resistance training at the initiation of GLP-1 therapy, not after muscle loss becomes apparent. 2
• Don't use GLP-1 therapy in older adults with unexplained weight loss or existing sarcopenia without aggressive muscle preservation strategies. 3, 6
• Don't rely on supplements alone. Protein and resistance training are the foundation; BCAAs, creatine, omega-3s, and vitamin D are adjuncts only if the foundation is insufficient. 1