Abstract
<title>Abstract</title> <p>Background Depression is highly prevalent among individuals with type 2 diabetes mellitus (T2DM) and is associated with adverse metabolic and cardiovascular outcomes. However, its impacts on insulin initiation and cardiovascular health remain insufficiently characterized across diverse healthcare settings. This retrospective multinational observational cohort study aims to evaluate associations of comorbid depression with insulin initiation and cardiovascular outcomes among individuals with T2DM. Methods Electronic health records from three academic medical center databases in Taiwan and South Korea, standardized to the Observational Medical Outcomes Partnership (OMOP) Common Data Model within the OHDSI network, were used. Eligible participants were adults with T2DM initiating oral antidiabetic therapy with at least 365 days of prior observation; those with prior insulin exposure, maternity-related conditions, schizophrenia, or bipolar disorder were excluded. The target cohort had comorbid depression (diagnosis plus antidepressant medication); the comparator cohort had no depression. Propensity score stratification balanced baseline characteristics. The primary outcome was insulin initiation (≥ 30 consecutive days); secondary outcomes were acute coronary syndrome (ACS), myocardial infarction (MI), and stroke. Cox proportional hazards models were used, with site-level hazard ratios pooled via random-effects meta-analysis. Results The final analytic population included 4725 patients with depression and 39,721 without depression. The meta-analysis demonstrated that depression was associated with an increased risk of insulin initiation (hazard ratio [HR] 1.77; 95% CI, 1.03–3.06). Elevated risks were also observed for ACS (HR 1.74; 95% CI, 1.17–2.59), MI (HR 1.31; 95% CI, 1.02–1.68), and stroke (HR 3.38; 95% CI, 1.41–8.12). These findings were directionally concordant across sensitivity analyses and databases. Conclusion Comorbid depression is associated with accelerated insulin initiation and increased cardiovascular risks in T2DM patients. Integration of mental health management into diabetes care may improve clinical outcomes.</p>