Systematic Review: Glucose Control and Cardiovascular Disease in Type 2 Diabetes

Background: Results from clinical trials examining the effect of intensive glucose control on cardiovascular disease have been conflicting. Purpose: To summarize clinical benefits and harms of intensive versus conventional glucose control for adults with type 2 diabetes. Data Sources: Studies were retrieved by systematically searching the MEDLINE database (January 1950 to April 2009) with no language restrictions. Study Selection: Two independent reviewers screened abstracts or full-text articles to identify randomized trials that compared clinical outcomes in patients with type 2 diabetes receiving intensive glucose control and those receiving conventional glucose control. Data Extraction: Two investigators independently abstracted data on study variables and outcomes, including severe hypoglycemia, cardiovascular disease, and all-cause mortality. Data Synthesis: 5 trials involving 27 802 adults were included. Intensive glucose targets were lower in the 3 most recent trials. Summary analyses showed that compared with conventional control, intensive glucose control reduced the risk for cardiovascular disease (relative risk [RR], 0.90 [95% CI, 0.83 to 0.98]; risk difference per 1000 patients per 5 years [RD], -15 [CI, -24 to -5]) but not cardiovascular death (RR, 0.97 [CI, 0.76 to 1.24]; RD, -3 [CI, -14 to 7]) or all-cause mortality (RR, 0.98 [CI, 0.84 to 1.15]; RD, -4 [CI, -17 to 10]). Intensive glucose control increased the risk for severe hypoglycemia (RR, 2.03 [CI, 1.46 to 2.81]; RD, 39 [CI, 7 to 71]). As was seen in the overall analyses, pooled findings from the early and more recent trials showed that intensive glucose control reduced the risk for cardiovascular disease and increased the risk for severe hypoglycemia. Limitation: Summary rather than individual data were pooled across trials. Conclusion: Intensive glucose control reduced the risk for some cardiovascular disease outcomes (such as nonfatal myocardial infarction), did not reduce the risk for cardiovascular death or allcause mortality, and increased the risk for severe hypoglycemia.