Semaglutide [sold as Ozempic, Wegovy or Rybelsus], a highly popular medication approved by the U.S. Food and Drug Administration to treat obesity and manage type 2 diabetes, was associated with a 49% to 73% lower risk of first-time or recurring suicidal ideations compared to other medications for controlling obesity and type 2 diabetes that work via different mechanisms.

These findings provide evidence that semaglutide — which helps regulate appetite and insulin levels by targeting glucagon-like peptide 1 receptors (GLP1R) in the body — does not appear to increase the risk of suicidal ideation, contrary to the claims of some anecdotal reports. Published [January 5] today in Nature Medicine and paired with a related Research Briefing, the study was co-led by scientists at Case Western Reserve University and the National Institute on Drug Abuse (NIDA), National Institutes of Health.

Outside of anecdotal and case reports, this association had not yet been explored by comprehensive studies. Recently, patients prescribed the medication for obesity (brand name Wegovy) or type 2 diabetes (brand name Ozempic), have anecdotally reported suicidal ideations resulting from semaglutide, and this has spurred European regulatory agencies to investigate this potential association.

Researchers examined electronic health records in the United States from 240,618 patients who were obese or overweight (mean age 50 years, 72.6% women) and who were prescribed semaglutide or another medication for weight loss between June 2021 and December 2022. Among this group, 232,771 patients did not have a prior history of suicidal ideation and 7,847 patients did.

The researchers also replicated the findings in 1,589,855 patients with type 2 diabetes (mean age 58 years, 49.2% women) who were prescribed either semaglutide or other medications for their condition between December 2017 and May 2021. This group included 1,572,885 patients without and 16,970 patients with a prior history of suicidal ideations.

For each study population, the semaglutide groups and the non-GLP1R groups had similarly matched demographic characteristics, medical history, problems with lifestyle, mental and substance use disorders, and prior suicidal ideation and behavior. 

Tracking the patients’ medical histories through six months after they were prescribed medication, the researchers found people prescribed semaglutide for weight loss had a 0.11% risk of first-time suicidal ideations (among those without a prior history) and approximately a 7% risk of recurrent suicidal ideation (among those with a prior history), compared to 0.43% and 14%, respectively, for the group prescribed other weight loss medications.

In patients with type 2 diabetes, semaglutide prescription was associated with 0.13% risk of first-time suicidal ideations and 10% for recurrent ideation, compared to 0.36% and 18%, respectively, for other diabetes medications. Compared with other medications, semaglutide was also associated with a lower risk of first-time suicidal ideation in patients with type 2 diabetes at longer follow-up durations (up to three years).

The authors concluded that their results do not support concerns of increased suicidal risk associated with semaglutide and highlight the need for a more detailed evaluation of reported cases to date. They recommend future studies evaluate potential longer-term associations of semaglutide with suicidal ideations in patients with obesity or type 2 diabetes – as well as in other at-risk populations – and explore any associations between semaglutide and suicide attempts.

The paper’s authorship was also supported by the National Institute on Aging, the National Institute on Alcohol Abuse and Alcoholism, and the National Cancer Institute at the NIH.

This news release was published by the National Institutes of Health on January 5, 2024.