Folks who take Ozempic or Wegovy for diabetes and weight loss need not worry about a higher risk of suicidal thoughts or feelings while on the medications, a new, large review finds.
In the study, which was funded by the U.S. National Institutes of Health, researchers turned to a database of more than 100 million patient records to measure the risks of suicidal ideation among people using semaglutide, which is sold as Ozempic for type 2 diabetes and Wegovy for weight loss.
The results were published Jan. 5 in the journal Nature Medicine.
Study author Dr. Rong Xu, a professor of biomedical informatics at Case Western Reserve University School of Medicine in Cleveland, told CNN that she decided to look into the issue after European regulators opened a probe into semaglutide and reports of suicidal thoughts last summer.
Just this week, a quarterly report from the U.S. Food and Drug Administration revealed that the agency is looking into similar reports among users of multiple weight-loss drugs, including Ozempic and Wegovy.
For the new review, Xu and her team, which included National Institute on Drug Abuse Director Dr. Nora Volkow, compared cases of suicidal ideation among people taking semaglutide with those taking other medicines for weight loss or diabetes.
"We observed a lower incidence of suicidal ideations in patients who had taken semaglutide than in patients who were treated with non-GLP1R-targeting medications for the same conditions,"Volkow told CNN. The GLP-1 receptor is what semaglutide targets.
The analysis included more than 240,000 people with obesity and more than 1.5 million with type 2 diabetes. It looked at the risk of suicidal ideation within six months of starting the medicines, as well as at later times.
At six months, it found that among people taking the drug for weight loss, semaglutide was linked to a 73% lower risk of first-time suicidal ideation and a 56% lower risk of recurrent suicidal ideation, CNN reported. The drugs that semaglutide was compared to included bupropion, naltrexone, orlistat, topiramate and phentermine.
For people with type 2 diabetes, the reductions were 64% and 49%, respectively, CNN reported. Here, the drugs that semaglutide was compared to included insulin, metformin and newer classes of medications known as DPP-4 and SGLT-2 inhibitors.
What exactly prompted the review?
As the use of Ozempic and Wegovy exploded over the past few years, Xu said she heard anecdotal reports of people experiencing a reduction in addictive behaviors while taking the medications -- showing less interest in things like alcohol or smoking.
"It was kind of like a paradox,"Xu said of the European probe into suicide and the anecdotal reports of less addictive behaviors.
With access to a database that includes de-identified electronic health records from 100.8 million people in 59 U.S. health systems, Xu said she decided to analyze the risk.
Ozempic and Wegovy, along with similar drugs like Mounjaro and Zepbound, are now being prescribed to millions of patients. The most common side effects are gastrointestinal issues like nausea, vomiting and constipation, although reports of more serious potential side effects, like stomach paralysis, have emerged.
Both Wegovy and Zepbound have warnings in their U.S. prescribing information about the risk of suicidal behavior and ideation. The prescribing information for an older medicine, Saxenda -- part of the same GLP-1 receptor class -- also recommends that patients be monitored for depression or suicidal thoughts or behavior, CNN reported.
Volkow also pointed to a previous weight-loss drug, rimonabant, that was withdrawn from the European market in 2008 over concerns about suicidal thoughts while taking the drug. She noted that rimonabant blocks a cannabinoid type 1 receptor "that, when blocked, can trigger negative emotional states."
She added it's also possible that effects of abrupt weight loss could "make some people vulnerable."
Even though semaglutide was associated with a lower risk of suicidal ideation in the latest study, Xu and Volkow wrote in a research briefing that the data "do not yet justify off-label treatment"for suicidal thoughts.
Still, Volkow noted, "there is interest in testing semaglutide as a potential treatment for depression."
In fact, at least one trial is now recruiting patients for that very purpose.
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SOURCE: Nature Medicine, Jan. 4, 2024; CNN