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GLP-1 Receptor Agonists for Weight Loss and Risk of Major Safety Outcomes: A Multicentre Cohort Study
Jisu Park1, Ju Hwan Kim1, Yoon Seob Kim2,3,4
1School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
Diabetes, Obesity & Metabolism
|July 6, 2026
Summary
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight loss showed increased risks for psychiatric and gastrointestinal issues. Careful patient selection and monitoring are crucial when prescribing these popular weight-management drugs.
Area of Science:
- Pharmacology
- Clinical Medicine
- Public Health
Background:
- Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for weight management.
- The clinical safety profile of GLP-1 RAs, particularly semaglutide and liraglutide, requires thorough investigation.
- Uncertainty exists regarding the real-world safety outcomes associated with these medications.
Purpose of the Study:
- To evaluate the safety of initiating semaglutide or liraglutide for weight loss.
- To assess the association between GLP-1 RA initiation and specific adverse safety outcomes.
- To compare safety profiles between semaglutide and liraglutide users and non-users.
Main Methods:
- A multicentre cohort study utilizing electronic health records from 13 South Korean hospitals (2018-2025).
- Data were mapped to the OMOP Common Data Model for standardized analysis.
- Propensity score matching was employed to compare new users of semaglutide or liraglutide with non-initiators, assessing ten predefined safety outcomes via Cox proportional hazards models and meta-analysis.
Main Results:
- Semaglutide initiation was linked to higher risks of psychiatric disorders (HR 2.02), gastrointestinal dysmotility/obstruction (HR 3.91), and vision impairment (HR 1.58).
- Liraglutide initiation was associated with increased risks of psychiatric disorders (HR 1.66), hepatic impairment (HR 1.46), pancreatobiliary disorders (HR 1.33), and vision impairment (HR 1.34).
- Sensitivity analyses generally supported these findings, though some associations, like semaglutide-related vision impairment and liraglutide-related hepatic impairment, showed variability.
Conclusions:
- Initiation of GLP-1 RAs for weight loss is associated with elevated risks of specific psychiatric and gastrointestinal adverse events.
- Significant heterogeneity in safety outcomes exists between different GLP-1 RA agents.
- These findings highlight the necessity for judicious patient selection and diligent monitoring during GLP-1 RA therapy for weight management.
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