BACKGROUND: Optimal glycated hemoglobin (HbA1c) targets for type 2 diabetes remain controversial. Given the evolution of modern antidiabetic therapies, this study aims to reevaluate optimal glycemic targets among patients receiving contemporary glucose-lowering treatments. METHODS: We conducted a retrospective cohort study using the National Taiwan University Hospital Integrated Medical Database, including 16 604 patients with type 2 diabetes who initiated dipeptidyl peptidase-4 inhibitors between 2009 and 2019, with follow-up through December 2021. Patients were categorized by long-term mean HbA1c quintiles. Outcomes included major adverse cardiovascular events (including ischemic stroke, myocardial infarction, cardiovascular death), renal outcomes (progression to dialysis, ≥50% estimated glomerular filtration rate decline, or doubling serum creatinine), hospitalization for heart failure, and safety outcomes. Associations were assessed using Cox proportional hazards models and restricted cubic spline analyses. RESULTS: Compared with the third quintile as reference, the fourth (hazard ratio HR, 1.22 95% CI, 1.01-1.47) and fifth quintiles (HR, 1.36 95% CI, 1.12-1.64) were associated with a significantly higher risk of major adverse cardiovascular events. Restricted cubic spline modeling identified significant J-shaped relationships for both major adverse cardiovascular events and renal outcomes, with the lowest risk observed around an HbA1c of 7%. In contrast, hospitalization for heart failure risk increased linearly with rising HbA1c levels. Notably, sex differences were identified: men showed a linear decrease in cardiovascular risk with lower HbA1c, whereas women exhibited a J-shaped relationship, indicating increased risks at both glycemic extremes. CONCLUSION: Optimal glycemic targets among patients receiving contemporary therapies differ by outcome and sex. Individualized HbA1c management strategies are essential to balance cardiovascular and renal benefits against potential risks.
Lin et al. (Wed,) studied this question.