Prior studies of type 1 diabetics and newly diagnosed type 2 diabetics have suggested long-term reduction in mortality and macrovascular event risk resulting from earlier periods of tight glucose control. In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, blood pressure control in patients with type 2 diabetes resulted in lower risk of death, macrovascular, and microvascular events. However, this study did not find similar benefit from tight glycemic control. The present study extends the observation of patients in this trial to 6-years after completion of the trial to assess for a long-term benefit associated with a period of tight glycemic control. Of the 10261 patients eligible for continuation, 8494 consented to continued observation. Between-group differences in blood pressure and glycemic control observed during the trial period were no longer evident by the first post-trial visit (median of 3.5 years after completion of the trial). Over a median follow-up of nearly 6 years (for a total of nearly 10 years including time in trial), patients in the blood pressure treatment group demonstrated a significant reduction in their risk of death or death from cardiovascular causes (HR=0.91, 95% CI, 0.84 to 0.99; P=0.03). Similar benefit was not observed for patients previously randomized to tight glycemic control (HR=1.00, 95% CI, 0.92 to 1.08). However, a period of tight glycemic control was associated with a lower risk of end-stage renal disease (HR 0.54; 95% CI, 0.34 to 0.85; P = 0.007).
Conclusions: In this large study of patients with established type 2 diabetes, a period of tight glycemic control was not associated with reduced mortality or macrovascular risk in 10-years of follow-up. In light of prior studies, these findings suggest the relative benefit of glycemic control may be influenced by how long a patient has had underlying diabetes. Relative to glycemic control, blood pressure control appears to be a larger contributor to reducing cardiovascular risk in patients with established diabetes.
Summarized by Hussain Contractor and Steven M. Bradley
Zoungas S1, Chalmers J, Neal B, Billot L, Li Q, Hirakawa Y, Arima H, Monaghan H, Joshi R, Colagiuri S, Cooper ME, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Lisheng L, Mancia G, Marre M, Matthews DR, Mogensen CE, Perkovic V, Poulter N, Rodgers A, Williams B, MacMahon S, Patel A, Woodward M; ADVANCE-ON Collaborative Group. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med. 2014 Oct 9;371(15):1392-406.