GLP-1 Receptor Agonists for Weight Loss and Risk of Major Safety Outcomes: A Multicentre Cohort Study

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for weight loss, yet their safety in clinical practice remains uncertain. We evaluated associations between weight-management semaglutide or liraglutide initiation and safety outcomes in a multicentre cohort.

We used electronic health records from 13 South Korean hospitals (2018-2025) mapped to the OMOP Common Data Model. Adults initiating semaglutide or liraglutide were compared with propensity score-matched non-initiators in a new-user design. Ten safety outcomes were assessed. Site-specific hazard ratios were estimated using Cox proportional hazards models and combined via meta-analysis.

After matching, 2357 semaglutide and 6953 liraglutide initiators were compared with 22 602 and 68 001 non-initiators, respectively. Semaglutide was associated with increased risks of psychiatric disorders overall (hazard ratio 2.02, 95% confidence interval 1.30-3.14), anxiety disorder (2.39, 1.22-4.71), depressive disorder (3.42, 1.51-7.74), gastrointestinal dysmotility or obstruction (3.91, 1.42-10.82), and vision impairment (1.58, 1.04-2.41). Liraglutide was associated with increased risks of psychiatric disorders overall (1.66, 1.36-2.03), anxiety disorder (1.68, 1.45-1.96), depressive disorder (1.51, 1.14-2.00), hepatic impairment (1.46, 1.16-1.83), pancreatobiliary disorder (1.33, 1.09-1.63), pancreatitis/cholangitis/cholelithiasis (1.40, 1.18-1.68), and vision impairment (1.34, 1.16-1.55). Sensitivity analyses were consistent overall, although semaglutide-associated vision impairment and liraglutide-associated hepatic impairment were not significant in some analyses.

GLP-1 RA initiation for weight loss was associated with higher risks of selected psychiatric and gastrointestinal outcomes compared with non-initiators, with heterogeneity across agents. These findings underscore the importance of careful patient selection and monitoring.