GIP/GLP-1 Receptor Agonists Linked to Reduced Overdose and Hospitalization Risk in Co-Occurring OUD/AUD

Co-occurring opioid use disorder (OUD) and alcohol use disorder (AUD) are significant public health challenges, leading to substantial morbidity and mortality. Despite the availability of effective medications for both OUD (MOUD) and AUD (MAUD), their utilization remains suboptimal. Emerging research suggests that glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (RAs), primarily prescribed for metabolic diseases like type 2 diabetes (T2DM) and obesity, may also influence substance-related outcomes by modulating reward pathways in the brain. This study explored the potential associations between GIP/GLP-1 RA prescriptions and adverse healthcare outcomes in this vulnerable population.

Researchers conducted a retrospective cohort study using de-identified electronic health records from 149 U.S. health systems (Oracle Health Real-World Data, 2014-2024). The study included 107,217 patients aged ≥12 years with dual OUD and AUD diagnoses. Time-varying exposures included prescriptions for MOUD, MAUD, and GIP/GLP-1 RA prescriptions. Outcomes were tracked over 2 years and included overdoses and intoxications, SUD-related hospitalizations, detoxification, positive drug screens, mental health events, incident liver conditions, and liver biomarkers. Marginal structural survival models with stabilized inverse probability of treatment weighting were used to estimate adjusted hazard ratios (aHRs), stratified by MOUD/MAUD status, T2DM, and obesity.

GIP/GLP-1 RA prescriptions were significantly associated with a lower risk of all-drug overdose, particularly among patients not receiving MOUD/MAUD (aHR 0.61; 95% CI 0.32-0.98). This indicates a 39% reduction in overdose risk in this subgroup. Stratified analyses further revealed protective associations in specific patient groups. For instance, a substantially lower overdose risk was observed among patients with T2DM receiving MAUD only (aHR 0.15; 95% CI 0.01-0.41), representing an 85% reduction. Patients receiving both MOUD and MAUD also showed reduced overdose risk, whether they had T2DM (aHR 0.46; 95% CI 0.24-0.87) or obesity (aHR 0.19; 95% CI 0.04-0.97). Protective associations for SUD-related hospitalization were consistently observed across most patient strata. These findings suggest a broad benefit of GIP/GLP-1 RAs in mitigating severe outcomes in individuals with co-occurring substance use disorders.

GIP/GLP-1 RA prescriptions were associated with a 39% lower risk of all-drug overdose (aHR 0.61; 95% CI 0.32-0.98) in patients not receiving standard OUD/AUD medications.