A large new study suggests that Ozempic and Wegovy don’t increase the risk of suicidal thoughts, a potential side effect that has prompted regulatory investigations in the United States and Europe.
Both drugs contain the same active ingredient, semaglutide, and are in a family of medicines known as GLP-1 receptor agonists, which can help control blood sugar levels and reduce hunger. Regulators in the United States, Europe, and the United Kingdom have said they’re investigating cases of suicidal thoughts (also called suicidal ideation) reported in some people who took Ozempic, Wegovy, and other GLP-1 drugs.
In the new study of more than 1.8 million U.S. patients, however, people on Wegovy and Ozempic had a 49 percent to 73 percent lower risk of suicidal thoughts than individuals who were taking other medicines for weight loss or type 2 diabetes, according to results published January 5 in Nature Medicine.
“These findings signal preliminary evidence for the safety of semaglutide for those with mental health conditions, who may be at greater risk of experiencing harm from side effects that cause suicidal thoughts,” says the senior study author, Rong Xu, PhD, the director of the center for artificial intelligence in drug discovery at Case Western Reserve University in Cleveland.
Lower Risk of Suicidal Thoughts With Semaglutide
Researchers examined electronic health records over the six months after people were prescribed semaglutide or a different medication for weight loss or for type 2 diabetes.
Nearly 1.6 million participants took semaglutide or another medicine for type 2 diabetes. For these people, 0.13 percent on semaglutide and 0.36 percent given other drugs experienced suicidal thoughts for the first time during the period examined in the study.
When people had a history of suicidal thoughts, 10 percent on semaglutide and 18 percent given different medicines had recurrent suicidal thoughts during the six months.
Among more than 240,000 participants prescribed medicines for weight loss, 0.11 percent of those on semaglutide had suicidal thoughts for the first time, compared with 0.43 percent for individuals taking different weight loss drugs.
When weight loss patients already had a history of suicidal thoughts, 7 percent on semaglutide experienced recurrent problems with this, compared with 14 percent of people prescribed different weight loss drugs.
The study wasn’t designed to prove whether or how different GLP-1 drugs or other medicines might directly cause or prevent suicidal thoughts or behaviors.
Weight and Mental Health
It’s not exactly clear why there have been cases of suicidal thoughts observed in some people taking drugs for weight loss, says Nora Volkow, MD, a coauthor of the new study and the director of the National Institute on Drug Abuse at the National Institutes of Health.
“Some speculate that it relates to a removal of food as a rewarding stimuli, or to the associated changes in peripheral hormones linked with weight loss,” Volkow says. “The lower level of risk of suicidal ideation in patients treated with semaglutide compared to patients treated with other anti-diabetes or anti-obesity medications could reflect the distinct mechanism of pharmacological action and merits further investigation.”
Shauna Levy, MD, the medical director of the Tulane Weight Loss Center in New Orleans, says the new study results mirror what she’s seen with her own patients.
“These results are consistent with what I have seen from my patients, in the sense that they feel happier after taking GLP-1 agonists,” says Dr. Levy, who wasn’t involved in the new study. “I have not had many patients with suicidal ideation in my practice.”
Levy agreed that the exact reason why semaglutide might mean less risk of suicidal thoughts isn’t clear. At least initially, weight loss can be associated with improved mood, at least in part because obesity is tied to higher rates of depression and anxiety.
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But more research is needed to pinpoint the precise reason for mood shifts associated with GLP-1 drugs in general or with semaglutide in particular.
In the meantime, Levy says the new study results won’t change how she treats patients. “It is still incredibly important to monitor patients carefully for any preexisting conditions or any changes in mental health following usage of GLP-1 agonists,” Levy says. “It is important that patients who are taking GLP-1 agonists are followed closely by a medical professional.”