Elevated Cardiovascular Risk and Mortality in Type 2 Diabetes Mellitus Patients With Cannabis, Opioid, and Cocaine Use Disorders

Aims To evaluate the association between substance use disorders (SUDs), cardiovascular disease (CVD), and all‐cause mortality in patients with type 2 diabetes mellitus (T2DM). Materials and Methods Using the TriNetX Research Network, we performed a retrospective cohort analysis of adults aged ≥ 18 years diagnosed with T2DM between January 2016 and December 2022. Patients diagnosed with cannabis‐, opioid‐, or cocaine‐related disorders within 1 year prior to their T2DM diagnosis were identified. Propensity score matching (PSM) was utilized to balance demographics, comorbidities, and medication use between the SUD and non‐SUD cohorts. Results After PSM, each group included 69 419 individuals. Over a 3‐year follow‐up period, the SUD cohort exhibited significantly elevated risks of acute myocardial infarction (HR 1.994; 95% CI 1.766–2.253), atrial fibrillation (HR 1.455; 95% CI 1.300–1.630), heart failure (HR 1.837; 95% CI 1.693–1.994), stroke (HR 1.524; 95% CI 1.354–1.715), and all‐cause mortality (HR 1.420; 95% CI 1.359–1.483). Subgroup analyses demonstrated consistent risk elevations across all substance types, with the highest relative mortality risk observed in patients with opioid‐related disorders. All associations were statistically significant ( p < 0.001). Conclusions Co‐occurring SUDs are strongly associated with increased risk of cardiovascular morbidity and all‐cause mortality in T2DM patients. However, these associations should be interpreted cautiously due to potential residual confounding despite propensity score matching. These findings underscore the urgent need for integrated risk assessment alongside tailored preventive and therapeutic strategies in this high‐risk population.