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People taking semaglutide had lower risk of suicidal thoughts

Researchers have been investigating concerns about the safety of semaglutide as they arise. myskin / Shutterstock

Semaglutide is a drug sold under the brand names Ozempic and Rybelsus for diabetes and Wegovy for weight loss. It belongs to a class of drugs called glucagon-like peptide 1 receptor (GLP1R) agonists. While these drugs have proven effective, concerns linger about their potential side effects. Recently, cases have been reported of suicidal thoughts associated with semaglutide. This has prompted investigations by regulatory agencies in Europe. 

A team of researchers led by Dr. Rong Xu at Case Western Reserve University and Dr. Nora Volkow, director of the National Institute on Drug Abuse (NIDA), used electronic health records to examine the relationship between semaglutide and suicidal thoughts. They compared semaglutide to other, non-GLP1R agonist drugs for diabetes and weight loss. Their findings appeared in Nature Medicine on January 5, 2024.

The team first analyzed electronic health records for more than 240,000 people with overweight or obesity. Most had no previous history of suicidal thoughts. Among this group, 0.11% of those prescribed semaglutide reported suicidal thoughts within the first six months. For those prescribed non-GLP1R agonists, the risk of suicidal thoughts was almost four times as great—0.43%. Among the almost 8,000 people with a prior history of suicidal thoughts, 6.5% of those prescribed semaglutide reported suicidal thoughts. More than twice as many prescribed non-GLP1R agonists, 14.1%, had such thoughts. These findings weren’t affected by sex, age, or ethnicity.

The researchers next analyzed records for more than 1.5 million people with type 2 diabetes. As in the group with overweight or obesity, people taking semaglutide had a lower risk of suicidal thoughts than those taking non-GLP1R agonist drugs. This was true independent of sex, age, or ethnicity, and in people both with and without a previous history of suicidal thoughts. The reduced risk associated with semaglutide lasted through up to three years of follow-up.

The findings do not support concerns that have been raised about an increased suicide risk associated with semaglutide. Previous reports of such an association may need to be examined in more detail.

“The exploding popularity of this drug makes it imperative to understand all its potential complications,” says co-author Dr. Pamela Davis. “It’s important to know that prior suggestions that the drug might trigger suicidal thoughts [are] not borne out in this very large and diverse population in the U.S.”

“Our study suggests semaglutide can be safe for those with mental health conditions,” Volkow says. “As researchers are also investigating semaglutide as a treatment for substance use disorders—which often co-occur with other mental health disorders—it is vital to ensure the medication is safe and does not place vulnerable groups at even greater risk of harmful health impacts.”

The authors recommend that future studies look at associations between semaglutide and suicidal thoughts over longer periods of time. They also suggest exploring any associations between semaglutide and suicide attempts.

—by Brian Doctrow, Ph.D.