Musculoskeletal Adverse Event Signals Associated With Semaglutide, Liraglutide, and Tirzepatide in the US FDA Adverse Event Reporting System.
- 1Osteopathic Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Clearwater, USA.
- 2Internal Medicine, Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Davie, USA.
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.
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BibTeX
@article{wadhwa2026musculoskeletal,
title = {{Musculoskeletal Adverse Event Signals Associated With Semaglutide, Liraglutide, and Tirzepatide in the US FDA Adverse Event Reporting System.}},
author = {Akshita Wadhwa and Dhruv Patel and Andrew Bouras and Sajan Shah and Sonia Daryanani},
journal = {Cureus},
year = {2026},
month = sep,
doi = {10.7759/cureus.116758},
url = {https://europepmc.org/article/MED/42921281},
note = {CC BY},
}
RIS
TY - JOUR
TI - Musculoskeletal Adverse Event Signals Associated With Semaglutide, Liraglutide, and Tirzepatide in the US FDA Adverse Event Reporting System.
AU - Akshita Wadhwa
AU - Dhruv Patel
AU - Andrew Bouras
AU - Sajan Shah
AU - Sonia Daryanani
PY - 2026
DA - 2026/09/22
JO - Cureus
DO - 10.7759/cureus.116758
UR - https://europepmc.org/article/MED/42921281
AB - 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.
SN - 2168-8184
ER -