Effects of intensive glycemic control on clinical outcomes among patients with type 2 diabetes with different levels of cardiovascular risk and hemoglobin A_1c in the ADVANCE trial

OBJECTIVE To study whether the effects of intensive glycemic control on major vascular outcomes (a composite of major macrovascular and major microvascular events), all-cause mortality, and severe hypoglycemia events differ among participants with different levels of 10-year risk of atherosclerotic cardiovascular disease (ASCVD) and hemoglobin A_1c (HbA_1c)atbaseline. RESEARCH DESIGN AND METHODS We studied the effects of more intensive glycemic control in 11,071 patients with type 2 diabetes (T2D), without missing values, in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, using Cox models. RESULTS During 5 years’ follow-up, intensive glycemic control reduced major vascular events (hazard ratio [HR] 0.90 [95% CI 0.83–0.98]), with the major driver being a reduction in the development of macroalbuminuria. There was no evidence of differences in the effect, regardless of baseline ASCVD risk or HbA_1c level (P for interaction 5 0.29 and 0.94, respectively). Similarly, the beneficial effects of intensive glycemic control on all-cause mortality were not significantly different across baseline ASCVD risk (P 5 0.15) or HbA_1c levels (P 5 0.87). The risks of severe hypoglycemic events were higher in the intensive glycemic control group compared with the standard glycemic control group (HR 1.85 [1.41–2.42]), with no significant heterogeneity across subgroups defined by ASCVD risk or HbA_1c at baseline (P 5 0.09 and 0.18, respectively). CONCLUSIONS The major benefits for patients with T2D in ADVANCE did not substantially differ across levels of baseline ASCVD risk and HbA_1c.