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Compared with other antidiabetic medications, semaglutide was linked to a significantly lower risk of opioid overdose in patients with diabetes and OUD.

Semaglutide was associated with a significantly lower risk of opioid overdose in patients with type 2 diabetes (T2D) and opioid use disorder (OUD). Compared with other antidiabetic medications, hazard ratios for overdose with semaglutide ranged from 0.32 to 0.71, depending on medication type, researchers reported in a research letter in JAMA Network Open.

The findings suggest semaglutide’s “potential therapeutic value for preventing overdoses,” wrote corresponding authors Rong Xu, PhD, and Nora D. Volkow, MD, and colleagues.

Researchers conducted the emulation target trial after hearing anecdotal reports of decreased drug cravings in patients taking semaglutide, a glucagon-like peptide-1 receptor agonist (GLP1-RA) prescribed for T2D and obesity. Empirical studies have shown the drug’s therapeutic benefit in easing cravings for alcohol and nicotine.

The cohort study included 33,006 patients with T2D and OUD who were prescribed antidiabetic medications between December 2017 and June 2023. Deidentified electronic health record data used in the study were from the TriNetX Analytics Platform.

Among patients, 3034 were prescribed semaglutide and 29,972 were prescribed other antidiabetic medications (insulin, metformin, dipeptidyl-peptidase-4 inhibitors [DPP-4is], sodium-glucose cotransporter-2 inhibitors (SGLT2is), sulfonylureas, thiazolidinediones, and other GLP-1RAs such as liraglutide and dulaglutide). Propensity-score matching balanced characteristics such as age, sex, ethnicity, and comorbidities between the groups.

Over a follow-up of 1 year, semaglutide was linked with a significantly lower risk of opioid overdose, according to the study. After propensity-score matching, hazard ratios for overdose with semaglutide were 0.32 versus thiazolidinediones, 0.37 versus DPP-4is, 0.42 versus insulin, 0.45 versus liraglutide, 0.46 versus metformin, 0.49 versus sulfonylureas, 0.56 versus other GLP-1RAs, 0.58 versus SGLT2is, and 0.71 versus dulaglutide.

Meanwhile, a negative control outcome—medical encounters for congenital malformations, deformations, and chromosomal abnormalities—did not differ between the groups.

Researchers acknowledged several study limitations, including the possibility of unmeasured confounders, biases, and limitations inherent in observational studies based on electronic health record data.

“Results need validation from other data resources and study populations,” they wrote. “Further research is warranted to investigate the underlying mechanisms, and randomized clinical trials are necessary to corroborate the clinical effects on OUD.”