Glycemic Control in Type 2 Diabetes: The Tighter the Better?

Abstract

Hemmingsen B, Christensen LL, Wetterslev J, Vaag A, Gluud C, Lund SS, Almdal T: Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomized clinical trials with meta-analyses and trial sequential analyses. BMJ 344:e1771, 2012 Objective. The goal of this meta-analysis was to determine the effect of intensive versus conventional glycemic control on all-cause mortality and cardiovascular mortality, nonfatal myocardial infarction (MI), microvascular complications, and severe hypoglycemia in patients with type 2 diabetes. Design and methods. This was a systematic review with both meta-analysis and trial-sequential analysis of randomized clinical trials. The researchers evaluated 28,614 participants with type 2 diabetes (15,269 randomized to intensive control and 13,345 randomized to conventional control). This analysis included 20 randomized trials, of which 14 dealt exclusively with glycemic control in the usual-care setting in patients without acute events at entry. Thirteen of the trials were published in English, and one was in Russian. The included trials were mainly conducted in North America and Europe. Ten of the trials described how the diagnosis of type 2 diabetes was established, whereas four did not describe how the diagnosis was made. Potential participants in the trials were excluded primarily for having liver, kidney, or other severe disease. The mean follow-up duration varied by study, although, for most, it was 5 years. Results. Compared to conventional glycemic management, intensive treatment of blood glucose did not reduce all-cause mortality (relative risk [RR] 1.02, 95% CI 0.91–1.13; 28,359 participants, 12 trials). Data were insufficient to suggest that intensive control reduces the risk of cardiovascular mortality (RR 1.11, 95% CI 0.92–1.35; 28,359 participants, 12 trials). Intensive treatment reduced the risk for nonfatal MI (RR 0.85, 95% CI 0.76–0.95, P = 0.004; 28,111 participants, 8 trials) in meta-analysis, but this was not confirmed …