Legacy Effect of Intensive Blood Glucose Control on Cardiovascular Outcomes in Patients With Type 2 Diabetes and Very High Risk or Secondary Prevention of Cardiovascular Disease: A Meta-analysis of Randomized Controlled Trials

Purpose

We performed a meta-analysis to investigate the legacy effect of >5 years of intensive blood glucose lowering on cardiovascular outcomes in patients with type 2 diabetes and very high risk or secondary prevention of cardiovascular disease (CVD).

Methods

We mainly searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials. Patients in the included studies had intensive glucose lowering for >5 years and posttrial follow-up for at least 5 years. Primary end points were all-cause mortality and cardiovascular death. Secondary end points were major macrovascular events, myocardial infarction, and stroke. We used risk ratios (RRs) with 95% CIs as summary statistics.

Findings

We included 3 trials that involved 13,684 patients, of whom 6805 received intensive glucose-lowering treatment and 6879 received standard treatment. The mean total follow-up duration was 10.3 years, which included 5.4 years of in-trial intervention and 5.5 years of posttrial follow-up. Intensive glucose control treatment did not significantly reduce all-cause mortality (RR = 0.98; 95% CI, 0.87–1.10) or cardiovascular death (RR = 0.97; 95% CI, 0.87–1.09). No significant risk reduction was found for stroke (RR = 1.02; 95% CI, 0.92–1.14), myocardial infarction (RR = 0.91; 95% CI, 0.75–1.09), or major macrovascular events (RR = 0.99; 95% CI, 0.93–1.06).

Implications

A legacy effect of >5-year intensive blood glucose control on cardiovascular outcomes in patients with type 2 diabetes and very high risk or secondary prevention of CVD was not detected, although this effect might be applicable in patients with diabetes and primary prevention of CVD. Further investigation of the legacy effect in different CVD risk populations should therefore be performed.