A cohort study found semaglutide was associated with a significantly lower risk of opioid overdose compared with other antidiabetic medications in patients with comorbid type 2 diabetes and opioid use disorder. 

The study, published in JAMA Network Open, used electronic health records from the TriNetX Analytics Platform to emulate a target trial comparing semaglutide to other antidiabetic medications.

The study included 33,006 eligible patients, with 3,034 prescribed semaglutide and 29,972 prescribed other antidiabetic medications. After propensity-score matching, semaglutide was associated with a lower risk of opioid overdose during a 1-year follow-up period compared with other antidiabetic medications, including other glucagon-like peptide-1 receptor agonists (GLP-1RAs).

Eligibility criteria included patients diagnosed with both type 2 diabetes (T2D) and opioid use disorder (OUD), prescribed semaglutide or other antidiabetic medications between December 2017 and June 2023, and with a history of obesity, hypertension, hypercholesterolemia, hyperlipidemia, heart diseases, or stroke. Exclusion criteria included bariatric surgery, pancreatitis, type 1 diabetes, thyroid cancer, or gastroparesis.

Patients were classified into semaglutide and other antidiabetes medication groups based on the first prescription during the study period. The semaglutide group and each comparison group were separately propensity-score matched for covariates at baseline to emulate randomization. The main outcome was opioid overdose, and a negative control outcome (medical encounters for congenital malformations, deformations, and chromosomal abnormalities) was also examined.

Before propensity-score matching, the semaglutide and comparison groups differed by age, sex, ethnicity, and comorbidity conditions. After matching, these characteristics were balanced. The study found semaglutide was associated with a significantly lower risk of opioid overdose during the 1-year follow-up compared with other antidiabetic medications, including Insulin, Metformin, Dipeptidyl-peptidase-4 inhibitors, Sodium-glucose cotransporter-2 inhibitors, Sulfonylureas, Thiazolidinediones, and other GLP-1RAs.

The negative control outcome showed no difference between groups.

The study's findings suggest semaglutide may have potential therapeutic value for preventing overdoses in patients with comorbid T2D and OUD. However, the authors note several limitations inherent to electronic health record-based observational studies, including potential unmeasured or uncontrolled confounders and biases.

The researchers emphasize the need for validation of these results using other data resources and study populations. They also called for further research to investigate the underlying mechanisms and recommended randomized clinical trials to corroborate the clinical effects of semaglutide on OUD.

The authors declared having no competing interests.