Evaluating the effect of metformin on sarcopenia: A Mendelian randomization study

Sarcopenia is prevalent among elder patients with type 2 diabetes. As a first-line medication for managing type 2 diabetes, metformin has shown controversial effects on sarcopenia. This study aims to analyze the impact of metformin on sarcopenia using Mendelian randomization analysis. We selected 30 single nucleotide polymorphisms associated with metformin used as instrumental variables from genome-wide association studies. Mendelian randomization was conducted using inverse variance weighted (IVW), Mendelian randomization Egger, and weighted median methods. Additionally, we performed heterogeneity tests, Pleiotropy analyses, and sensitivity analyses to validate our findings. The IVW method indicated a P-value of .63 and an odds ratio (OR) of 0.93 (95% CI: 0.69-1.25) for the relationship between metformin use and walking pace. For appendicular lean mass, the IVW method showed a P-value of .42 and an OR of 0.69 (95% CI: 0.28-1.70). In contrast, the IVW analysis indicated a significant relationship between metformin use and right hand grip strength, with P-value of .01 and OR (95% CI) = 0.64 (0.45-0.91), as well as for left hand grip strength, with P-value of .01 and OR (95% CI) = 0.65 (0.45-0.92). Notably, a causal relationship was established between metformin use and lower hand grip strength, while no causal relationship was found between metformin use and walking pace or appendicular lean mass. This study suggests that caution is needed regarding long-term metformin use in the context of sarcopenia.