Risk of suicidal ideation and suicidality among adults prescribed semaglutide for weight management: A...

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).

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.

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).

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.