Patients taking semaglutide for obesity or diabetes appear to have a lower risk of suicidal ideation than those who are taking other drugs for these conditions, according to a report in Nature Medicine.
Semaglutide is a glucagon-like peptide 1 receptor (GLP1R) agonist that was initially approved to treat diabetes (brand name: Ozempic) but was subsequently approved at a higher dose as a weight loss medication (brand name: Wegovy).
“Instructions for Wegovy include recommended monitoring for suicidal ideation. However, the association of semaglutide with suicidal ideation compared with non-GLP1R agonist medications has not been investigated,” wrote William Wang of Case Western Reserve University; Nora Volkow, M.D., director of the National Institute on Drug Abuse; and colleagues.
Wang, Volkow, and colleagues conducted a retrospective cohort study of electronic health records from the TriNetX Analytics Network, which includes data from more than 100 million patients across the United States. They identified 240,618 patients who were prescribed either semaglutide or a non-GLP1R anti-obesity medication (for example, bupropion) between June 2021 (when Wegovy was approved) and December 2022. They also identified 1,589,855 patients who received semaglutide or a non-GLP1R medication for type 2 diabetes (for example, metformin) between December 2017 (when Ozempic was approved) and May 2021. For both populations, the researchers examined the incidence of either a first or recurrent episode of suicidal ideation within six months of starting treatment.
Overall, patients who took semaglutide for overweight or obesity had a 73% reduced risk of new suicidal ideation compared with patients taking a non-GLP1R medication. Among the subset of patients with a history of suicidal ideation, those taking semaglutide had a 56% reduced risk of recurrent suicidal ideation compared with those taking a non-GLP1R medication. Semaglutide’s reduced risk of suicidal ideation was evident in both males and females, Black and White individuals, and across age groups.
A similar pattern of reduced suicidal ideation was seen among patients taking semaglutide for diabetes compared with non-GLP1R medications (64% reduced risk of new suicidal ideation and 49% reduced risk of recurrent ideation). Additional analysis revealed that the lower risk of suicidal ideation in patients taking semaglutide for diabetes persisted for up to three years after initiating treatment.
Wang, Volkow, and colleagues noted several limitations of the study, including missing information in the electronic health records about dosages of the medications taken and medication adherence. “Future controlled trials are necessary to assess any causal relationships between semaglutide with suicidal ideation,” they wrote.