Semaglutide Linked to Lower Risk of Suicidal Ideation in Patients with Obesity, Type 2 Diabetes

Semaglutide was associated with a lower risk of first-time and recurrent suicidal ideations in patients with obesity or overweight or type 2 diabetes (T2D), according to data from a recent retrospective analysis of the 2 patient populations.¹

Findings published in Nature Medicine showed that among 240 618 participants who were obese or overweight, those taking semaglutide had a significantly lower risk of suicidal ideation compared with those who received non-glucagon-like peptide 1 receptor (GLP1R) agonist antiobesity medications (0.11% vs 0.43%; hazard ratio [HR] 0.27, 95% CI 0.20-0.36).¹

Similarly, in the second cohort of 1 589 855 patients with T2D, results showed that the semaglutide group had a significantly lower risk for incident suicidal ideation than the matched non-GLP1R agonist antiobesity medication group (0.13% vs 0.36%; HR 0.36, 95% CI 0.25-0.53), according to corresponding author Nora Volkow, MD, director, National Institute on Drug Abuse, and colleagues.¹

“Previous concerns raised by case reports associating semaglutide with suicidal ideations has led to an investigation by the European Medicines Agency,” wrote researchers in separate research briefing on the study. “In contrast to these case reports, this cohort study found that semaglutide did not further increase the risk of suicidal ideations compared with other weight loss or anti-diabetes medications. This study contributes to the evidence base regarding safety profiles of real-world semaglutide use.”²

For the current study, Volkow and colleagues used US electronic health records from the TriNetX Analytics Network. They followed participants for 6 months to examine the first incidence and relapse of suicidal ideations, according to the study.¹

The first cohort consisted of 240 628 patients with obesity or overweight (mean age, 50.1 years, 72.6% women, 16% Black) and were prescribed semaglutide or non-GLP1R agonist antiobesity medications from June 2021 through December 2022. Among the cohort, 232 771 individuals did not have a history of suicidal ideation and 7847 did.¹

In the second analysis, investigators replicated the original investigation with 1 589 855 patients with T2D (mean age, 57.5 years, 49.2% women, 15.4% Black) who were prescribed semaglutide or non-GLP1R antidiabetes medications from December 2017 through May 2021. Among this cohort, 1 572 885 participants did not have a prior history of suicidal ideation and 16 970 did.¹

Patients in both cohorts were matched for demographic characteristics, medical history, lifestyle issues, mental and substance use disorders, and prior suicidal ideation and behavior, according to researchers.¹

In addition to the findings on incident suicidal ideations as mentioned previously, results showed similar data on the association between semaglutide and the risk of recurrent suicidal ideation. Patients with obesity or overweight who received semaglutide had a significantly lower risk of recurrent suicidal ideation compared with those taking other non-GLP1R agonist obesity medications (6.5% vs 14.1%; HR 0.44, 95% CI 0.32-0.60).¹

“Further studies should evaluate the association of semaglutide and other GLP1R agonist medications with the incidence and recurrence of suicidality in other at-risk populations,” concluded Volkow et al.¹

References:

1. Wang W, Volkow ND, Berger NA, et al. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Nat Med. Published online January 5, 2024. doi:10.1038/s41591-023-02672-2

2. Semaglutide and risk of suicidal ideations. Nat Med. Published online January 5, 2024. doi:10.1038/s41591-023-02691-z