Semaglutide a Potential Treatment Option for OUD?

Semaglutide (Ozempic, Novo Nordisk) is associated with a significantly lower risk for overdose in individuals with opioid use disorder (OUD), new research shows.

The findings suggest that the drug may be a promising treatment option for OUD, adding to the growing evidence of the potential psychiatric benefits of glucagon-like peptide 1 (GLP-1) inhibitors.

“Our study provided real-world evidence suggesting that semaglutide could have benefits in preventing opioid overdose and treating opioid use disorder,” co-lead author Rong Xu, PhD, director of the Center for Artificial Intelligence in Drug Discovery at Case Western Reserve University School of Medicine, Cleveland, Ohio, told Medscape Medical News.

However, Xu cautioned that this evidence is preliminary and randomized clinical trials are required to confirm these findings.

The study published online in a research letter on September 25 in JAMA Network Open.

New Addiction Meds an Urgent Priority

Investigators analyzed electronic medical records from 33,006 patients with type 2 diabetes and OUD who were prescribed one of eight antidiabetic medications between 2017 and 2023. 

Drugs included in the study were semaglutide, insulin, metformin, albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, dipeptidyl-peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, and thiazolidinediones. 

Participants in the semaglutide and each comparison group were matched for certain covariates at baseline, such as socioeconomic status and OUD medications. 

After 1 year, semaglutide was associated with a 42%-68% lower risk of opioid overdose compared with other antidiabetic medications, including other GLP-1s (range of hazard ratio [HR]: HR, 0.32; 95% CI, 0.12-0.89; to HR, 0.58; 95%CI, 0.38-0.87). 

Xu noted a number of study limitations including the effect of possible confounders and sole reliance on prescription data.

However, the findings are in line with those of prior studies showing that semaglutide may be associated with lower rates of alcohol and nicotine use, she said. 

Earlier this year, Xu, along with National Institute on Drug Abuse Director Nora Volkow, MD, and colleagues, published a retrospective cohort study of nearly 84,000 patients with obesity. That analysis showed that semaglutide was associated with a significantly lower risk of new alcohol use disorder diagnoses. 

In a previous editorial by Xu and Volkow that summarized the research to-date on GLP-1s for nicotine, alcohol, and substance use disorders, they note that “closing the addiction treatment gap and discovering new, more effective addiction medications are urgent priorities. In this regard, investigating the potential of GLP-1 analogue medications to treat substance use disorder deserves fast and rigorous testing.”

Caution Warranted

Commenting on the study for Medscape Medical News, Riccardo De Giorgi, MD, PhD, department of psychiatry, University of Oxford in the Oxford, United Kingdom, said at this point, “we have to be very careful about how we interpret these data.” 

In August, De Giorgi published a study showing that semaglutide was associated with reduced risk for several neurologic and psychiatric outcomes including dementia and nicotine misuse. 

While there is enough observational evidence linking GLP-1 medications with reduced SUD risk, he noted that “now is the time to move on and conduct some randomized clinical trials, specifically testing our hypothesis in people who have psychiatric disorders.”

De Giorgi also called for mechanistic studies of semaglutide and other so that researchers could learn more about how it works to reduce cravings. “Instead of going from bench to bed, we need to go back to the bench,” he said.

As previously reported by Medscape Medical News, De Giorgi recently called on experts in the field to actively explore the potential of GLP-1 inhibitors for mental illness. 

The study was funded by National Institute on Alcohol Abuse and Alcoholism, National Institute on Aging, the National Center for Advancing Translational Sciences, and the Intramural Research Program of the National Institutes of Health. Xu reported no relevant financial relationships. De Giorgi reported receiving funding from the National Institute for Health Research Oxford Health Biomedical Research Centre.