Abstract
AIMS: To evaluate the risk of incident suicidal ideation (SI) and suicidality (SI, suicide attempt or intentional self-harm) among overweight or obese adults who were prescribed semaglutide for weight management compared with active comparators (weight management drugs: bupropion/naltrexone, orlistat, phentermine or phentermine/topiramate). MATERIALS AND METHODS: Using the Merative® MarketScan Databases, we conducted a retrospective cohort study of adults initiating semaglutide or an active comparator between 01 June 2021, and 31 December 2022. Patients were required to have ≥1 year of continuous health and pharmacy plan coverage, a diagnosis of overweight or obesity, no prior suicidality or type 2 diabetes, and new users of semaglutide or active comparators for inclusion. SI and suicidality were identified using diagnosis codes within 183 days of drug initiation. Kaplan-Meier analysis was used to estimate risks, risk differences (RDs), and risk ratios (RRs), controlling for confounding with standardized mortality ratio weights. RESULTS: Among 16 822 semaglutide and 11 986 active comparator new users, the adjusted risk of incident SI was 0.08% (13.0 events) for semaglutide and 0.05% (8.9 events) for active comparators, and for incident suicidality was 0.08% (14.0 events) for semaglutide and 0.07% (11.0 events) for active comparators. Adjusted RDs were 0.02% (95% CI: [-0.02%, 0.07%]) for SI and 0.02% (-0.03%, 0.07%) for suicidality, with corresponding RRs of 1.36 (0.62, 6.14) and 1.18 (0.57, 3.63). CONCLUSION: Among patients initiating semaglutide for weight management, semaglutide did not appear to increase the risk of suicide-related outcomes. However, the CIs of the RDs are compatible with a 0.07% increase in 6-month risk and the true RD could be larger due to the potentially low sensitivity of ICD-10 diagnosis codes for and underreporting of suicide-related outcomes. Additional studies are critical to confirm these findings and obtain more precise estimates of any potential benefits or harms of semaglutide.