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Musculoskeletal Adverse Event Signals Associated With Semaglutide, Liraglutide, and Tirzepatide in the US FDA Adverse Event Reporting System

Year: 2026

Type: article

Abstract: BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes and obesity, yet their musculoskeletal reporting profile remains incompletely characterized. Lean-mass loss during treatment has raised concern about muscle atrophy and related complications. METHODS: In this retrospective cross-sectional pharmacovigilance study, we analyzed 20,006,989 safety reports in the Food and Drug Administration Adverse Event Reporting System (FAERS) with initial receipt dates through January 27, 2026. Semaglutide, liraglutide, tirzepatide, and six dipeptidyl peptidase-4 or sodium-glucose cotransporter-2 inhibitors were each evaluated against all other eligible FAERS reports. These were not direct comparisons between drugs. Reporting odds ratios (RORs) and proportional reporting ratios (PRRs) were calculated across 30 Medical Dictionary for Regulatory Activities preferred terms. Signals were defined using the ROR criterion, with PRR providing supporting evidence. RESULTS: Eight ROR-defined signals were identified among the three incretin-based therapies. Muscle atrophy showed the strongest disproportionality for semaglutide (ROR 3.96, 95% confidence interval (CI) 3.42-4.59; n = 182) and tirzepatide (ROR 2.29, 95% CI 1.96-2.67; n = 163), and both met the ROR and PRR thresholds. Additional lower-magnitude ROR signals included back pain, muscle spasms, and neck pain for semaglutide, and back pain, osteoarthritis, and neck pain for liraglutide. The muscle atrophy signal persisted in serious-report analyses for semaglutide (ROR 2.63; n = 85) and tirzepatide (ROR 2.06; n = 33). Among reports with recorded sex, female patients accounted for 1,398 of 2,187 liraglutide reports (63.9%), 2,654 of 3,853 semaglutide reports (68.9%), and 1,816 of 2,294 tirzepatide reports (79.2%). CONCLUSIONS: Semaglutide and tirzepatide showed muscle atrophy reporting signals that persisted when the analysis was restricted to reports classified as serious. Prospective studies are needed to investigate these findings. These data cannot show whether the drugs cause muscle atrophy or how often it occurs among treated patients.

Source: Cureus

DOI: 10.7759/cureus.116758

Authors: Akshita Wadhwa, Dhruv Patel, Andrew Bouras, Sajan Shah, Sonia Daryanani

Institution: Nova Southeastern University

Language: English

Topic: Pharmacovigilance and Adverse Drug Reactions

Subfield: Toxicology

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W7214063520