Major adverse cardiac events and mortality associated with ADHD and its treatment in adults with type 2 diabetes: a multi-national cohort study

Abstract Background Attention-deficit/hyperactivity disorder (ADHD) has been linked to elevated risk of type 2 diabetes (T2D). However, the impact of ADHD and ADHD medication use on prognosis and health outcomes in T2D remains unclear. This study investigates the associations of (1) ADHD and (2) ADHD medication use with rates of major adverse cardiac events (MACE) and all-cause mortality after a T2D diagnosis. Methods This multinational cohort study used population-based data from Australia, Denmark, the Netherlands, Norway, Sweden, the United Kingdom, and the United States. Using a standardized analytical protocol, we identified adults with a first recorded T2D diagnosis during 2010-2020. Exposures were (1) ADHD, defined by a recorded ADHD diagnosis or ADHD medication dispensation, and (2) among adults with ADHD, the use of ADHD medication, both analysed as time-varying exposures. Main outcomes were MACE (acute myocardial infarction, stroke, or cardiovascular disease-related death) and all-cause mortality after T2D diagnosis. Cause-specific Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs); results were pooled using random-effects meta-analyses and stratified by age and sex. Results The cohort included 1,929,027 adults with T2D (909,176 [47.1%] males). In pooled analyses, adults with T2D and ADHD had a higher rate of all-cause mortality (HR, 2.42; 95% CI, 1.72-3.41), but not MACE (HR, 1.04; 95% CI, 0.81-1.35), after a T2D diagnosis compared with those without ADHD. Among adults with T2D and ADHD, ADHD medication use was associated with higher rate of MACE in those diagnosed with T2D before age 45 years (HR, 1.58; 95% CI, 1.18-2.10). These associations remained consistent, after adjusting for sex, age, calendar year at T2D diagnosis, psychiatric history, other psychotropic medication use, and cardiometabolic medication use. Conclusions Adults with T2D and co-occurring ADHD were found to have increased risk of all-cause mortality after T2D diagnosis, while ADHD was not consistently associated with MACE across countries. ADHD medication use was linked to higher rate of MACE in adults with early-onset T2D. These findings suggest the potential need for integrated somatic-psychiatric care and careful consideration of ADHD medication use that may help reduce MACE and mortality, particularly in younger-onset T2D.