Association of GLP-1 receptor agonists with intentional self-harm in patients with type 2 diabetes: a Sentinel Distributed Database study

INTRODUCTION: The U.S. Food and Drug Administration (FDA) investigated the potential risk of suicidal ideation and behaviors for glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on learning of post-marketing reports of suicidal ideation and behaviors in patients taking GLP-1 RAs. This study assessed a potential association with intentional self-harm comparing GLP-1 RAs to other antidiabetic products. RESEARCH DESIGN AND METHODS: We conducted an active-comparator, new-user cohort study-using FDA's Sentinel System-with data from October 1, 2015, to September 30, 2023. The study included health plan members ≥18 years old diagnosed with type 2 diabetes, newly initiated GLP-1 RAs (n=1 161 983), sodium-glucose cotransporter-2 inhibitors (SGLT-2is, n=1 081 155), or dipeptidyl peptidase-4 inhibitors (DPP-4is, n=1 396 382), and continuously enrolled in a health plan with medical and drug coverage for ≥183 days. The main outcome was intentional self-harm. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for intentional self-harm events and used inverse probability of treatment weighting of propensity scores to control for confounding. RESULTS: The comparator groups had a mean age that was slightly above 60 years and similar percentages of males and females. Adjusted incidence rates of intentional self-harm per 1000 person-years were 1.13 for GLP-1 RAs, 1.22 for SGLT-2is, and 1.37 for DPP-4is. Adjusted HRs indicated no increased risk of intentional self-harm comparing GLP-1 RAs to SGLT-2is (HR 0.93; 95% CI 0.81 to 1.08) or DPP-4is (HR 0.94; 95% CI 0.82 to 1.07). Subgroup analyses by comorbid obesity and diabetes, psychiatric history, prior intentional self-harm, age, and sex yielded similar results. CONCLUSIONS: The use of GLP-1 RAs did not show increased risk of intentional self-harm compared with SGLT-2is or DPP-4is, which provides some reassurance regarding the safety of GLP-1 RA use in patients with type 2 diabetes.