Exploring the protective effect of metformin against sarcopenia: insights from cohort studies and genetics.

Background: The impact of metformin on sarcopenia remains uncertain. This study aimed to investigate whether metformin influences sarcopenia risk and evaluate the effects of potential drug targets on sarcopenia traits.

Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) (n = 3549) to assess the association between metformin use and sarcopenia risk in elderly patients with type 2 diabetes. Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) from UK Biobank (n = 1,366,167) and FinnGen (n = 218,007), with expression quantitative trait loci (eQTL) as instrumental variables, examined the causal effect of metformin-related targets on sarcopenia traits, while molecular docking explored the interaction between metformin and its drug targets.

Results: Metformin use was associated with increased grip strength (OR = 2.46; 95% CI 1.49-2.38) and skeletal muscle mass (OR = 1.24; 95% CI 0.20-2.28), as well as reduced mortality (HR = 0.62; 95% CI 0.54-0.71). MR analysis suggested a possible link between GDF15 gene expression and sarcopenia traits, with no evidence of genetic confounding. Molecular docking indicated stable binding between metformin and GDF15.

Conclusion: This study suggests that metformin may lower sarcopenia risk, particularly in elderly patients with type 2 diabetes, with GDF15 identified as a promising target for sarcopenia treatment.