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

Akshita Wadhwa; Dhruv Patel; Andrew Bouras; Sajan Shah; Sonia Daryanani

doi:10.7759/cureus.116758

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

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e116758
Journal	Cureus
DOIs	https://doi.org/10.7759/cureus.116758
State	Published - Sep 22 2026

Funding

Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

ASJC Scopus Subject Areas

Pharmacology
Internal Medicine
Endocrinology, Diabetes and Metabolism

Keywords

adverse event reporting
glucagon-like peptide-1 receptor agonists
muscle atrophy
musculoskeletal adverse events
pharmacovigilance

Disciplines

Pharmacology
Internal Medicine
Endocrinology, Diabetes, and Metabolism

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520968-musculoskeletal-adverse-event-signals-associated-with-semaglutide-liraglutide-and-tirzepatide-in-the-us-fda-adverse-event-reporting-systemFinal published version, 521 KBLicense: CC BY

Cite this

@article{c1cfac37d5674e3d807c18711d087a90,

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

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.",

keywords = "adverse event reporting, glucagon-like peptide-1 receptor agonists, muscle atrophy, musculoskeletal adverse events, pharmacovigilance",

author = "Akshita Wadhwa and Dhruv Patel and Andrew Bouras and Sajan Shah and Sonia Daryanani",

year = "2026",

month = sep,

day = "22",

doi = "10.7759/cureus.116758",

language = "English",

journal = "Cureus",

issn = "2168-8184",

publisher = "Cureus, Inc.",

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TY - JOUR

T1 - Musculoskeletal Adverse Event Signals Associated With Semaglutide, Liraglutide, and Tirzepatide in the US FDA Adverse Event Reporting System

AU - Wadhwa, Akshita

AU - Patel, Dhruv

AU - Bouras, Andrew

AU - Shah, Sajan

AU - Daryanani, Sonia

PY - 2026/9/22

Y1 - 2026/9/22

N2 - 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.

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.

KW - adverse event reporting

KW - glucagon-like peptide-1 receptor agonists

KW - muscle atrophy

KW - musculoskeletal adverse events

KW - pharmacovigilance

U2 - 10.7759/cureus.116758

DO - 10.7759/cureus.116758

M3 - Article

SN - 2168-8184

JO - Cureus

JF - Cureus

M1 - e116758

ER -