Use of the medicine semaglutide for weight loss or type 2 diabetes wasn’t associated with a higher risk of suicidal ideation than other medicines for those conditions in a large new review of US health records that was backed by the National Institutes of Health.
The researchers used a database that includes more than 100 million patient records to assess the risks of suicidal ideation among people using the drug, sold as Ozempic for type 2 diabetes and Wegovy for weight loss. The results were published Friday in the journal Nature Medicine.
Dr. Rong Xu, an author of the study and professor of biomedical informatics at Case Western Reserve University School of Medicine, said she decided to look into the issue after European regulators opened a probe into semaglutide and reports of suicidal thoughts last summer. The US Food and Drug Administration said this week that it’s also conducting its own investigation.
Xu and her fellow researchers, including 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 wrote in an email, referring to the way semaglutide works to mimic a hormone called GLP-1.
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 longer time points.
At six months, it found that among people taking the drug for weight loss, semaglutide was associated with a 73% lower risk of first-time suicidal ideation and a 56% lower risk of recurrent suicidal ideation. The comparator drugs included bupropion, naltrexone, orlistat, topiramate and phentermine.
For people with type 2 diabetes, the reductions were 64% and 49%, respectively. The comparator drugs included insulin, metformin and newer classes known as DPP-4 and SGLT-2 inhibitors.
The lower risks were observed out to three years.
A positive effect on mental health?
The comparator medicines work differently than semaglutide, which is a GLP-1 receptor agonist that has effects on insulin production, appetite and feelings of fullness. Researchers have noted that it also has effects on the brain.
As use of Ozempic and Wegovy has exploded over the past few years, Xu said, she noted anecdotal reports of people experiencing a reduction in addictive behaviors while taking them – less interest in things like alcohol or smoking – which made her wonder whether the medicines could also have a positive effect on mental health.
How to get help
“It was kind of like a paradox,” Xu said. “The case reports from both sides”: the European investigation and these anecdotal reports.
With access to a database called the TriNetX platform, which includes de-identified electronic health records from 100.8 million people in 59 health systems across the US that’s updated “basically in real time, every day,” Xu decided to perform statistical analyses to assess the risk.
It’s an approach she says she used during the Covid-19 pandemic to evaluate the risk of the Omicron variant in real time.
Ozempic and Wegovy, along with similar drugs like Mou