Semaglutide Associated With Reduced Risk of Opioid Overdose in Patients With Type 2 Diabetes, Opioid Use Disorder

Results from a recent trial demonstrate the potential of semaglutide (Ozempic, Wegovy; Novo Nordisk) to reduce the risk of opioid overdose in patients with comorbid type 2 diabetes (T2D) and opioid use disorder (OUD), according to a research letter published in JAMA Network Open.¹

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Aside from acting as a weight-loss agent and treatment for T2D, semaglutide has showed effectiveness in treating a variety of conditions. In a recent study, semaglutide showed positive benefits to prevent heart attacks and other major adverse cardiac events. Earlier this year, the FDA approved a new indication for the drug to reduce the risk of cardiovascular disease complications.^2,3

However, it’s effectiveness as a treatment for OUD has yet to be examined. Empirical evidence has been published indicating the therapeutic benefit of semaglutide for alcohol use disorder (AUD) due to the reduced desire to drink in patients treated with the drug. In patients with and without T2D, consistent reductions in AUD were observed with semaglutide compared with other non-glucagon-like peptide-1 receptor agonists (GLP1-RAs) (0.32% vs 0.52%; HR: 0.56, 95% CI: 0.43-0.74).⁴

Patients oftentimes face obstacles to receiving medications for OUD, with many of them discontinuing treatment within 6 months. Given the urgency for alternative treatments for OUD as overdose fatalities in the United States remain elevated, the investigators sought to determine whether semaglutide could indeed protect against overdoses in patients with OUD.¹

The emulation target trial compared the association of semgalutide with opioid overdose risk in patients with comorbid T2D and OUD versus other antidiabetic medications. These included insulin, metformin, and other GLP1-RAs. In total, the study included the health records of 33,006 eligible patients; 3034 were prescribed semaglutide and 29,972 were prescribed other antidiabetic treatments.¹

Semaglutide was found to be associated with a significantly lower risk of opioid overdose during a 1-year follow-up compared with other antidiabetic medications, with hazard ratios ranging from 0.32 (95% CI, 0.12-0.89) to 0.58 (95% CI, 0.38-0.87). Importantly, the negative control outcome indicated no differences between the groups. Overall, these results suggest the potential therapeutic value of the drug.¹

Some limitations encountered by the investigators included potential unmeasured or uncontrolled confounders in the trial, as well as the potential for biases. Additionally, there are inherent limitations involved with using electronic health records in an observational study that the investigators recognized. Based on these limitations, the investigators called for validation through other data resources and study cohorts.¹

“Further research is warranted to investigate the underlying mechanisms, and randomized clinical trials are necessary to corroborate the clinical effects on OUD,” the study authors concluded.¹

REFERENCES

1. Wang W, Volkow ND, Wang Q, et al. Semaglutide and opioid overdose risk in patients with type 2 diabetes and opioid use disorder. JAMA Netw Open. 2024;7(9):e2435247. doi:10.1001/jamanetworkopen.2024.35247

2. Gallagher A. SELECT trial shows similar cardiac benefits of semaglutide for heart failure. Pharmacy Times. Published August 23, 2024. Accessed October 1, 2024. https://www.pharmacytimes.com/view/select-trial-shows-similar-cardiac-benefits-of-semaglutide-for-heart-failure

3. Gallagher A. FDA approves semaglutide for new indication involving cardiovascular disease. Pharmacy Times. Published March 8, 2024. Accessed October 1, 2024. https://www.pharmacytimes.com/view/fda-approves-semaglutide-for-new-indication-involving-cardiovascular-disease

4. Wang W, Volkow ND, Berger NA, et al. Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. Nature Comm. 2024;15:4548. doi:10.1038/s41467-024-48780-6