Clinical Question: Does intensive glucose lowering in patients with type 2 diabetes decrease their risk of death or sequelae of diabetes?

Bottom Line: Combining the results of 13 trials enrolling more than 34,500 patients, this meta-analysis found no benefit to attempting intensive glucose lowering in adults with type 2 diabetes, with the exception of a decrease in the likelihood of nonfatal myocardial infarction (but not cardiovascular mortality). The more studies that accumulate, the less benefit is shown with intensive glucose lowering. (Level of Evidence: 1a-)

Reference: Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 2011;343:d4169.

Study Design: Meta-analysis (randomized controlled trials)

Funding Source: Government

Setting: Various (meta-analysis)

Synopsis: These French investigators searched 3 databases, including the Cochrane Database, as well as reference lists of other meta-analyses, to identify randomized controlled trials assessing intensive glucose lowering treatment versus standard care or less intensive treatment. Two investigators independently evaluated the studies for inclusion, extracted the data, and assessed the quality of the research. They included 13 trials of 34,533 patients. Attempting intensive glucose lowering did not affect mortality (risk ratio = 1.04; 99% CI, 0.91-1.19) or cardiovascular death (risk ratio = 1.11; 0.86 - 1.43), though nonfatal myocardial infarction risk was lower with treatment (risk ratio = 0.85; 0.74-0.96). On the other hand, severe hypoglycemia (low enough to require medical intervention) was doubled in the intensive treatment group (risk ratio = 2.33; 1.62 - 3.36). Over 5 years, the risk of severe hypoglycemia requiring medical treatment ranged from 1.9% to 6.6% of patients. Restricting the analysis to only high-quality studies removed heterogeneity but also removed the benefit seen for nonfatal myocardial infarction risk. It did not change other results but revealed a 47% increase in the risk of heart failure. Microvascular effects of diabetes -- retinopathy, renal failure, and amputation -- were not affected by intensive glucose lowering, but there was heterogeneity among the results related to the quality of the trial. Removing the results of the oft-maligned University Group Diabetes Project did not affect the results.