No Increased Risk of Suicidal Ideation With GLP-1 Drugs

Despite recent concerns to the contrary, semaglutide (Wegovy, Ozempic) carried a lower risk of suicidal ideation in patients with obesity or type 2 diabetes, according to retrospective analyses of the two patient populations.

An analysis of 240,618 patients who were overweight or obese showed that those taking semaglutide — a glucagon-like peptide 1 (GLP-1) receptor agonist — had a significantly lower risk of suicidal ideation compared with those on non-GLP-1 anti-obesity medications (0.11% vs 0.43%; HR 0.27, 95% CI 0.20-0.36), according to Nora Volkow, MD, director of the National Institute on Drug Abuse, and colleagues.

Similarly, an analysis of 1,572,885 patients with type 2 diabetes revealed that those taking semaglutide had a significantly lower risk of suicidal ideation compared with patients taking other anti-diabetes medications (0.13% vs 0.36%; HR 0.36, 95% CI 0.25-0.53), they reported in Nature Medicine.

“Our analyses do not support concerns of increased risk of suicidal ideation with semaglutide,” Volkow and co-authors wrote, noting that the results “do not support the concerns of increased suicidal risk associated with semaglutide raised by the [European Medicines Agency] and the Medicines and Healthcare Products Regulatory Agency in the United Kingdom.”

“This highlights the need for a more detailed evaluation of the previously reported cases,” the researchers added.

Those recent case reports suggested a possible association between semaglutide and suicidal ideation, prompting the investigations by regulatory agencies in Europe.

In a separate research briefing on the study, the Nature Medicine editorial team wrote that these results reveal a different outlook on the risks of semaglutide treatment.

“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,” they wrote. “This study contributes to the evidence base regarding safety profiles of real-world semaglutide use.”

To conduct the analyses, the researchers used U.S. electronic health records from the TriNetX Analytics Network.

In the first analysis, they assessed 240,628 patients who were overweight or obese and were prescribed semaglutide or non-GLP-1 receptor agonist anti-obesity medications for weight loss from June 2021 through December 2022. The patients had a mean age of 50 years and 72.6% were women. Among the cohort, 232,771 patients did not have a history of suicidal ideation.

In the second analysis, they replicated the original investigation with 1,572,855 patients with type 2 diabetes who were prescribed semaglutide or non-GLP-1 anti-diabetes medications from December 2017 through May 2021. Those patients had a mean age of 58 years and 49.2% were women. Similar to the obesity cohort, the majority of patients in this cohort did not have a prior history of suicidal ideation.

Patients in both analyses were matched for demographic characteristics, medical history, lifestyle issues, mental and substance use disorders, and prior suicidal ideation and behavior.

In addition to the findings on incidence of suicidal ideation, the authors found similar associations between semaglutide and recurrent suicidal ideation in a 6-month follow-up analysis of both cohorts.

Patients who were obese or overweight taking semaglutide also had a significantly lower risk of recurrent suicidal ideation compared with those taking non-GLP-1 anti-obesity medications (6.5% vs 14.1%; HR 0.44, 95% CI 0.32-0.60), the authors reported.

Similarly, patients with type 2 diabetes taking semaglutide had a significantly lower risk for recurrent suicidal thoughts when compared with similar patients taking non-GLP-1 anti-diabetes medications (10% vs 17.9%; HR 0.51, 95% CI 0.31-0.83).

The authors noted use of electronic medical records limited their ability to account for a patient’s medication adherence. They were also unable to evaluate the association between semaglutide and suicide attempts because the sample sizes were too small.

“Because suicide attempt is critically different from suicidal ideation, future studies should continue to evaluate the associations between semaglutide and suicide attempt and non-suicidal self-injury,” the researchers wrote.

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