1862-LB: Glucagon-Like Peptide 1 Receptor Agonists and the Risk of Suicide and Self-Harm among Patients with Type 2 Diabetes

Introduction & Objective: Increased reports of thoughts of suicide and self-harm among users of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have prompted multiple regulatory agencies to conduct reviews on the drug class. There is an urgent need to assess the safety of these drugs in a real-world setting. We sought to determine whether GLP-1 RA use is associated with an increased risk of suicide and self-harm when compared with dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes.

Methods: Using primary care, hospitalization and mortality data from the United Kingdom, we assembled a cohort of patients with type 2 diabetes newly prescribed GLP-1 RAs or DPP-4 inhibitors between January 2007 and December 2020. We used propensity score fine stratification weighting to balance the exposure groups on over 40 potential confounders, including age, sex, smoking, BMI, history of mental health disorders and behaviours associated with self-harm and suicide attempt, socioeconomic status, proxies for diabetes severity, common comorbidities, other medication use, and markers of health-seeking behaviour. Patients were followed using an on-treatment exposure definition. We fit weighted Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident suicide or self-harm.

Results: The cohort included 36,083 new users of GLP-1 RAs and 234,186 new users of DPP-4 inhibitors. Crude analyses indicated a twofold increase in the risk of suicide and self-harm associated with GLP-1 RA use (HR 1.99, 95% CI 1.65-2.41); however, the weighted model showed no increased risk (HR 0.99, 95% CI 0.77-1.29).

Conclusions: The use of GLP-1 RAs was not associated with an increased risk of suicide or self-harm in this large, population-based study from the United Kingdom. Increased reporting of thoughts of suicide and self-harm are likely due to confounding factors rather than a causal relationship.