AIMS/HYPOTHESIS: To investigate whether the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in methadone-treated patients with opioid use disorder (OUD) and type 2 diabetes (T2D) is associated with improved cardiometabolic and mental health outcomes.
METHODS: This retrospective population-based cohort study of adults (≥ 18 years) on methadone with both OUD and T2D (hemoglobin A ≥ 6.5%) was conducted between January 1, 2015, and October 1, 2024, using the TriNetX database. The cohort was divided into two groups, adjusted for baseline characteristics through propensity score matching (PSM), based on whether the individuals had received GLP1-RA prescriptions. Cox proportional hazard regression models were used to evaluate the association between GLP-1 RAs and the risk of incident physical and mental health outcomes over a one-year follow-up period. 1c
RESULTS: After PSM, 1,157 patients (mean [SD] age, 57.3 [11.1] years; 577 females [49.9%]) were prescribed GLP-1 RAs. Use of GLP-1 RAs was associated with a decreased incidence of myocardial infarctions (hazard ratios [HR], 0.58; 95% CI, 0.41-0.80) and hypoglycemia (HR, 0.50; 95% CI, 0.33-0.77). Patients treated with GLP-1 RAs were more likely to enter OUD remission (HR, 1.75; 95% CI, 1.24-2.47) and fewer had episodes of major depression (HR, 0.71; 95% CI, 0.61-0.81), anxiety disorders (HR, 0.77; 95% CI, 0.67-0.88), and suicidal thoughts or behaviors (HR, 0.27; 95% CI, 0.16-0.47).
CONCLUSIONS/INTERPRETATION: GLP-1 RA use in adults on methadone with both OUD and T2D was associated with lower rates of cardiometabolic and mental health complications. Randomized prospective trials are warranted to ascertain causality and clinical efficacy.
RESEARCH-IN-CONTEXT: Methadone-treated patients with opioid use disorder (OUD) and type 2 diabetes mellitus (T2D) represent a particularly high-risk group for metabolic complications, yet the potential benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) remain unclear. We examined whether GLP-1 RAs are associated with improved cardiometabolic and mental health outcomes among these patients. In the large, propensity score-matched cohort study of 2,314 methadone-treated patients with OUD and T2D, GLP-1 RAs use was associated with lower rates of myocardial infarctions, hypoglycemia, emergency department visits, and hospitalizations, along with higher rates of OUD remission and lower risks of opioid-related overdose, depression, and anxiety. Our findings indicate that GLP-1 RAs may mitigate cardiometabolic and mental health complications in methadone-treated patients with OUD and T2D, highlighting a potential therapeutic role for incretin-based drugs in opioid-related harm reduction in this high-risk population.
