Global Pharmacovigilance Signals for Liraglutide and Semaglutide in Obesity: A VigiBase Disproportionality Analysis

Objective: To compare disproportionality signals for liraglutide and semaglutide using VigiBase.Methods: Reports through September 2024 with Saxenda or Wegovy as suspect drugs were analyzed; Ozempic reports were excluded.A case/non-case design estimated age-and sex-adjusted reporting odds ratios (aRORs) and Information Components (ICs).Signals were defined as ≥3 reports with both the lower 95% confidence limit of the aROR >1 and IC025 >0.Comparators were all other anti-obesity medications (AOMs), non-GLP-1 AOMs, and the other drug; subgroup analyses were conducted.Results: Analyses included 117,987 reports for liraglutide (n=46,950) and 67,936 for semaglutide (n=39,992).Liraglutide showed signals for gallbladder and biliary tract disorders, acute pancreatitis, malignant neoplasms, and thyroid cancer; malignant neoplasms had the highest aROR [aROR 7.12 (95% CI 6.31 to 8.02); IC 1.05 (95% CI 0.95 to 1.15)].Semaglutide showed signals for optic nerve disorders, gastrointestinal obstruction, and acute pancreatitis; gastrointestinal obstruction had the highest aROR [aROR 4.45 (95% CI 2.11 to 9.39); IC 0.60 (95% CI 0.13 to 1.06)].With non-GLP-1 comparators, all five liraglutide signals persisted, whereas semaglutide showed signals for gallbladder disorders [aROR 7.44 (95% CI 4.18 to 13.25); IC 0.18 (95% CI 0.00 to 0.35)] and acute pancreatitis [aROR 19.07 (95% CI 10.21 to 35.60); IC 0.20 (95% CI 0.09 to 0.31)].Direct comparison identified semaglutide signals for suicide/self-harm [aROR 2.81 (95% CI 2.22 to 3.55); IC 0.29 (95% CI 0.09 to 0.48)], optic nerve disorders [aROR 2.09 (95% CI 1.71 to 2.55); IC 0.33 (95% CI 0.17 to 0.48)], and acute pancreatitis [aROR 1.40 (95% CI 1.25 to 1.57); IC 0.19 (95% CI 0.09 to 0.30)].Subgroup patterns varied.Conclusion: Liraglutide and semaglutide showed comparator-dependent reporting patterns requiring confirmation in population-based studies.(PeRM 2026;18:183-198)