International journal of molecular sciencesApr 14, 2026

Comparing Side Effect Reports for Tirzepatide, Semaglutide, and Liraglutide by Body System in Post-Marketing Data

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 15, 2026

Abstract

Tirzepatide is associated with higher odds of immune and hepatobiliary disorders compared to semaglutide and musculoskeletal and psychiatric disorders compared to liraglutide.

After analysis, 20 significant reporting patterns were identified for tirzepatide compared to semaglutide, and 23 for tirzepatide compared to liraglutide.
Eight reporting patterns remained significant across all analytical conditions.
Tirzepatide had higher reporting odds for immune disorders (ROR 1.97) and hepatobiliary disorders (ROR 1.71) compared to semaglutide.
Compared to liraglutide, tirzepatide showed higher odds for musculoskeletal disorders (ROR 2.02) and psychiatric disorders (ROR 2.14), but lower odds for neoplasms (ROR 0.28).
Heterogeneous reporting patterns for tirzepatide indicate consistent excess reporting for hepatobiliary, immune, and musculoskeletal disorders.

Simplified

Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist, introduces a mechanistically distinct approach within incretin-based therapies. While its efficacy is established, real-world data comparing post-marketing safety with established GLP-1 receptor agonists remain limited. This study assessed System Organ Class (SOC)-level reporting patterns for tirzepatide versus semaglutide and liraglutide using EudraVigilance data. Aggregated individual case safety reports (ICSRs) were analyzed using pairwise disproportionality analyses based on a case/non-case approach. Reporting odds ratios (RORs) with 95% confidence intervals were calculated. False discovery rate (FDR) correction using the Benjamini-Hochberg procedure and sensitivity analyses restricted to serious and healthcare professional-reported cases were performed to assess robustness. After FDR adjustment, 20 SOCs were significant in tirzepatide-semaglutide and 23 in tirzepatide-liraglutide comparisons; eight SOCs remained significant across all analytical conditions. Compared with semaglutide, tirzepatide showed higher reporting for immune (ROR 1.97, 95% CI 1.75-2.21) and hepatobiliary disorders (ROR 1.71, 95% CI 1.61-1.82). Versus liraglutide, higher odds occurred for musculoskeletal (ROR 2.02, 95% CI 1.85-2.21) and psychiatric disorders (ROR 2.14, 95% CI 1.99-2.30), and lower odds for neoplasms (ROR 0.28, 95% CI 0.26-0.31). Tirzepatide shows heterogeneous reporting patterns compared with GLP-1 receptor agonists, with consistent excess reporting for hepatobiliary, immune, and musculoskeletal disorders. These findings are hypothesis-generating and warrant confirmation in exposure-adjusted studies.

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Comparing Side Effect Reports for Tirzepatide, Semaglutide, and Liraglutide by Body System in Post-Marketing Data

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