Semaglutide linked to lower suicidal ideation risk than other obesity, diabetes drugs
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Key takeaways:
- Adults with obesity or type 2 diabetes receiving semaglutide have a lower risk for suicidal ideation than those taking non-GLP-1 medications.
- More studies are needed to assess possible causal associations.
Adults receiving semaglutide as a type 2 diabetes or obesity medication have a lower risk for suicidal ideation than those who are using a drug that is not a GLP-1 receptor agonist, according to findings published in Nature Medicine.
“Anecdotal reports of suicidal thoughts emerging from patients that use semaglutide signaled the need for particular attention to this potential association,” Nora Volkow, MD, director of the National Institute on Drug Abuse at the NIH, told Healio. “Our study is one answer to this call, and we did not find evidence to substantiate concerns of increased suicidal risk following reports of suicidal ideations from semaglutide use.”
Volkow and colleagues collected electronic health record data from the TriNetX analytics platform based on the Research U.S. Collaborative Network. Data were obtained from adults with overweight or obesity who were prescribed semaglutide (Wegovy, Novo Nordisk) or a non-GLP-1 receptor agonist obesity medication from June 2021 to December 2022. Data were also collected for adults with type 2 diabetes who were prescribed semaglutide (Ozempic, Novo Nordisk) or a non-GLP-1 receptor agonist diabetes therapy from December 2017 to May 2021. Researchers analyzed suicidal ideation incidence among adults with no history of suicidal ideation, and recurrence of suicidal ideation for those who had a history of suicidal ideation prior to being prescribed their diabetes or obesity medication. Participants in the semaglutide and non-GLP-1 groups were selected using propensity score matching with covariates that were considered potential risk factors for suicidal ideation.
“Suicide is among the top 10 leading causes of death worldwide,” Rong Xu, PhD, professor and director of the Center for Artificial Intelligence in Drug Discovery at Case Western Reserve University School of Medicine, told Healio. “Semaglutide is dispensed as either an anti-diabetes or an anti-obesity medication, with Wegovy being an immensely popular weight management strategy. Any concerns of potential risk for suicidal ideations associated with semaglutide can be of critical importance.”
Semaglutide lowers suicidal ideation risk
There were 52,783 adults with overweight or obesity and no history of suicidal ideation who received semaglutide matched with 52,783 adults who received a non-GLP-1 receptor agonist for the treatment of obesity. The semaglutide group had a lower risk for incident suicidal ideation than the non-GLP-1 group (HR = 0.27; 95% CI, 0.2-0.36). There were no suicide attempts in the semaglutide group vs. 14 reported suicide attempts for those receiving other obesity medications at 6 months (P < .001). Among 1,730 adults with a history of suicidal ideation, the semaglutide group had lower risk for recurrent suicidal ideation than the placebo group (HR = 0.44; 95% CI, 0.32-0.6).
Among adults with type 2 diabetes without a history of suicidal ideation, 27,726 adults receiving semaglutide were matched with 27,726 adults receiving a non-GLP-1 medication. Adults receiving semaglutide had a lower risk for incident suicidal ideation than those receiving a non-GLP-1 diabetes therapy (HR = 0.36; 95% CI, 0.25-0.53). Among 502 adults with type 2 diabetes and history of suicidal ideation, a lower risk for recurrent suicidal ideation was observed for the semaglutide group compared with those taking a non-GLP-1 medication (HR = 0.51; 95% CI, 0.31-0.83).
“Our findings, while they require replication, do not support concerns that semaglutide might increase suicidal ideations in patients being treated for their obesity or diabetes compared to other medications used for these indications,” Volkow said. “Regardless, they highlight the importance for screening for suicidal ideations in patients with obesity and diabetes so that proper support can be given to those at risk, and to ensure that studies like ours that evaluate long-term effects of semaglutide or other medications can properly evaluate potential suicidal risk.”
Among adults with type 2 diabetes who had longer follow-up data available, those receiving semaglutide had a lower risk for suicidal ideation at 1 year (HR = 0.39; 95% CI, 0.28-0.53), 2 years (HR = 0.53; 95% CI, 0.41-0.67) and 3 years (HR = 0.58; 95% CI, 0.49-0.72).
More studies needed
The researchers noted the findings serve as preliminary evidence that semaglutide may be a safer medication for adults who have suicidal ideation or other mental health conditions. However, Xu said more studies are needed to confirm the findings.
“Although patients prescribed semaglutide had lower risk of suicidal-ideation incidence and recurrence, our data do not yet justify off-label treatment,” Xu said. “Future controlled trials are necessary to assess any causal relationships between semaglutide and other GLP-1 receptor agonist medications with suicidal ideations.”
For more information:
Nora Volkow, MD, can be reached at nvolkow@nida.nih.gov.
Rong Xu, PhD, can be reached at rxx@case.edu.
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