Muscle Atrophy-Related Adverse Events of Antidiabetic Drug Classes: A Pharmacovigilance Analysis Using VigiBase Data.

Abstract

BACKGROUND Diabetes mellitus-a chronic metabolic disorder associated with an increased risk of muscle atrophy-can significantly impact patients' quality of life and overall health outcomes. While antidiabetic medications are crucial for managing blood glucose levels, some have been linked to muscle-related adverse events, potentially exacerbating the already elevated risk of muscle deterioration in diabetic patients. However, a comprehensive analysis of muscle atrophy-related adverse events across different classes of antidiabetic drugs has been lacking. Therefore, this study investigates the profile of muscle atrophy-related adverse events across major antidiabetic drug classes using the World Health Organization's (WHO's) Individual Case Safety Reports database. METHODS A pharmacovigilance analysis was conducted using data from VigiBase, the WHO's global reporting database, from 1968 to September 2025. The study examined adverse event signals related to muscle atrophy, sarcopenia, muscular weakness and motor function decline for nine classes of antidiabetic medications. Reporting odds ratios (RORs) were calculated to assess signal detection, and co-occurrence patterns of adverse events were analysed. RESULTS Among 41 551 306 adverse event reports, 2 095 847 were related to antidiabetic medications. Safety signals for muscle atrophy were detected with sulfonylureas (ROR: 1.2, 95% CI: 1.01-1.43, p = 0.042), GLP-1 analogues (ROR: 1.2, 95% CI: 1.02-1.41, p = 0.031) and SGLT2 inhibitors (ROR: 1.5, 95% CI: 1.19-1.78, p < 0.001). SGLT2 inhibitors also showed a signal for sarcopenia (ROR: 6.2, 95% CI: 3.71-10.3, p < 0.001). Biguanides demonstrated signals for muscular weakness (ROR: 1.6, 95% CI: 1.54-1.71, p < 0.001) and motor function decline (ROR: 1.7, 95% CI: 1.41-2.13, p < 0.001). Thiazolidinediones, glinides, DPP-4 inhibitors and alpha-glucosidase inhibitors showed no safety signals for the examined adverse events. Additionally, co-occurrence analysis revealed frequent associations between muscle atrophy and nausea/vomiting, falls and decreased appetite across different drug classes. CONCLUSIONS These findings indicate notable differences in the profiles of muscle atrophy-related adverse events among major classes of antidiabetic drugs, suggesting that drug selection may influence the risk of muscle function decline in patients. Clinicians should consider these safety profiles when prescribing antidiabetic therapies; however, causal relationships cannot be inferred solely from pharmacovigilance data. Further studies are warranted to establish causality between antidiabetic drug use and muscle-related adverse events and to elucidate the underlying mechanisms.