Association of inadequately controlled hypothyroidism with major adverse cardiovascular events in type 2 diabetes patients receiving levothyroxine: a retrospective cohort study.

PURPOSE: To evaluate whether levothyroxine (LT4) therapy is associated with major adverse cardiovascular events (MACE) in adults with type 2 diabetes. METHODS: We conducted a retrospective cohort study using the multi-institutional Chang Gung Research Database (2006-2017). New LT4 users were direct covariate matching with a 1:1 ratio to nonusers by age, sex, and index date, excluding patients with prior LT4 exposure or prior MACE. The primary outcome was MACE-nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization-with follow-up from the index date to the first event or 31 December 2017. Baseline comorbidities, concomitant medications, and laboratory parameters were assessed; Cox models estimated hazard in the matched cohort. Prespecified subgroup analyses examined age, sex, hypertension, diabetic microvascular complications, and end-stage renal disease. RESULTS: Compared with matched nonusers, LT4 users had a higher incidence of MACE, with higher rates of nonfatal stroke and heart failure hospitalization. In subgroup analyses, LT4 use, older age, male sex, hypertension, diabetic microvascular complications, and end-stage renal disease were associated with increased MACE risk. CONCLUSION: In adults with type 2 diabetes, the increased risk of MACE observed in patients receiving LT4 appears to be driven by inadequately controlled hypothyroidism rather than the medication itself. These findings underscore the critical importance of achieving and maintaining euthyroidism through careful LT4 dosing and active thyroid-function monitoring to mitigate cardiovascular risk in this high-risk population.