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.