Worldwide burden of antidiabetic drug-induced sarcopenia: An international pharmacovigilance study

Sarcopenia is a condition that poses a significant risk in the older population, with diabetes identified as a risk factor. Recent evidence suggests that GLP-1 RA, commonly used as antidiabetic treatments, may potentially induce sarcopenia. This study aimed to investigate the association between sarcopenia and various antidiabetic drugs, including GLP-1 RAs.

This study analyzed reports from the World Health Organization international pharmacovigilance database, covering the period from 1967 to 2023 (total reports, n = 131,255,418). We analyzed the reported odds ratio (ROR) and information component (IC) to evaluate the association between sarcopenia and seven classes of antidiabetic drugs: DPP-4 inhibitors, GLP-1 RAs, insulin, metformin, SGLT2 inhibitors, sulfonylureas, and thiazolidinediones.

Reports of antidiabetic drugs-associated sarcopenia have gradually increased (n = 508; 258 males [50.79 %]). Overall, antidiabetic drugs showed significant associations with sarcopenia (ROR, 1.31 [95 % CI, 1.20-1.44]; IC, 0.38 [IC₀₂₅, 0.24]). Among the individual drug classes, SGLT2 inhibitors showed the highest association (ROR, 2.49 [95 % CI, 1.93-3.22]; IC, 1.30 [IC₀₂₅, 0.87]), followed by metformin (ROR, 1.86 [95 % CI, 1.43-2.41]; IC, 0.88 [IC₀₂₅, 0.44]), DPP-4 inhibitors (ROR, 1.67 [95 % CI, 1.17-2.38]; IC, 0.72 [IC₀₂₅, 0.12]), and insulin (ROR, 1.27 [95 % CI, 1.11-1.45]; IC, 0.34 [IC₀₂₅, 0.11]). Despite the high number of reports for GLP-1 RAs, no significant association with sarcopenia was observed (n = 93; ROR, 1.06 [95 % CI, 0.86-1.29]; IC, 0.08 [IC₀₂₅, -0.27]).

Antidiabetic drugs showed significant associations with sarcopenia, with SGLT2 inhibitors exhibiting the strongest association. Notably, despite numerous reports, GLP-1 RAs did not show a significant association.