medwireNews: Data from a large retrospective analysis of electronic health records indicate that semaglutide is not associated with a higher risk for suicidal ideation relative to non-glucagon-like peptide (GLP)-1 receptor agonist anti-obesity or antidiabetic medications.
“Contrary to reports of increases in suicidal ideation with semaglutide, our analyses revealed a lower risk for both incidence and recurrence of suicidal ideation in patients prescribed semaglutide compared with [non-GLP-1 receptor agonist] anti-obesity and anti-diabetes medications,” write Nora Volkow (National Institutes of Health, Bethesda, Maryland, USA) and co-authors in Nature Medicine.
They explain that concerns over reports of suicidal ideation associated with semaglutide treatment have led to investigations by the European Medicines Agency (EMA) and the UK’s Medicines and Healthcare products Regulatory Agency. The US FDA has also received unverified reports of suicidal ideation associated with semaglutide through its Event Reporting System.
Yet, no studies have previously investigated the association of semaglutide with suicidal ideation relative to non-GLP-1 receptor agonist medications.
To address this, Volkow and team reviewed the electronic health records of 240,618 patients with overweight or obesity (mean age 50 years, 73% women) who were prescribed semaglutide or non-GLP-1 receptor agonist anti-obesity medications – bupropion, naltrexone, orlistat, topiramate, phentermine, or setmelanotide – between June 2021 and December 2022.
After propensity score-matching, they found that individuals given semaglutide had a significant 73% lower risk for incident suicidal ideation and a significant 56% lower risk for recurrent suicidal ideation at 6 months than those given non-GLP-1 receptor agonist anti-obesity medications. Specifically, people with no history of suicidal ideation had 6-month incidence rates of 0.11% and 0.43%, respectively. The rates were a corresponding 6.5% and 14.1% among people who had previously reported suicidal ideation and the results for both outcomes were consistent across subgroups stratified by age, sex, and ethnicity.
The researchers observed similar findings among 1,589,855 patients with type 2 diabetes (mean age 58 years, 49% women). In this cohort, people given semaglutide had significant 64% and 49% lower risks for incident and recurrent suicidal ideation at 6 months, respectively, than those given non-GLP-1 receptor agonist antidiabetic medications, namely insulin, metformin, sulfonylureas, alpha glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, or sodium glucose co-transporter 2 inhibitors.
Among people with no history of suicidal ideation, the 6-month incidence was 0.13% in the semaglutide group and 0.36% in the comparator group. For recurrent suicidal ideation, the rates were 10.0% and 17.9%, respectively.
The investigators were also able to look at longer follow-up periods in the type 2 diabetes cohort. At 1 year, the risk for suicidal ideation was a significant 61% lower with semaglutide than with non-GLP-1 receptor agonist antidiabetic medications. The association was attenuated, but still significant, at 2 and 3 years, with risk reductions of 47% and 42%, respectively.
Volkow et al conclude that their data “do not support the concerns of increased suicidal risk associated with semaglutide raised by the EMA and Medicines and Healthcare Products Regulatory Agency in the United Kingdom.”
They add that the findings highlight “the need for a more detailed evaluation of the previously reported cases.”
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