Introduction and Objective: Chronic opioid use is associated with high risk of overdose and developing substance use disorder. GLP-1RAs may influence reward-related neurobehavioral pathways, however, their real-world effects on opioid-related outcomes are unclear. We evaluated the association between GLP-1RA use and risk of opioid overdose among individuals with chronic opioid use.Methods: Using US claims data, we identified adults with chronic opioid use, defined as ≥90 days of any opioid use in the 180 days before and on the cohort entry, which was defined as date of initiation of GLP-1RA or SGLT-2i. The primary outcome was opioid overdose, and secondary outcomes included alcohol abuse/dependence and substance use disorders. Incidence rates (IR) and hazard ratios (HR) were estimated using Cox proportional hazards models in 1:1 propensity score-matched cohorts.Results: GLP-1RA initiation was associated with a lower risk of opioid overdose compared with SGLT-2i use (HR 0.70, 95% CI 0.51-0.99). Reduced risks were also observed for alcohol abuse/dependence (HR 0.77, 95% CI 0.64-0.93) and severe substance use disorder (HR 0.84, 95% CI 0.72-0.97). No association was observed for the negative control outcome of influenza vaccination.Conclusion: In a high-risk population with chronic opioid use, GLP-1RA initiation was associated with decreased risk of opioid overdose compared with SGLT-2i, supporting a potential neurobehavioral effect beyond glycemic control or weight loss.
S. Bea: None. E. Patorno: Research Support; Current; Boehringer Ingelheim International GmbH, AstraZeneca, Bayer AG, National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute. Other – Royalties; Current; UpToDate. S. Kattinakere Sreedhara: None. D. Wexler: Other – Data Monitoring Committee; Ended; Novo Nordisk. Other – Data Monitoring Committee; Current; Amgen Inc. S. Cromer: Other – Spouse is employee of Depuy Synthes; Current; Johnson & Johnson. J. Paik: None. K. Bykov: None.
American Diabetes Association (1-25-PDF-66), National Institute of Health (K01AG068365)
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