Abstract
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-April 2009) with no language restrictions. STUDY SELECTION: Two independent reviewers screened abstracts or full text articles to identify randomized trials comparing clinical outcomes in type-2 diabetes patients treated with intensive compared to 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: Five trials involving 27,802 adults were included. Intensive glucose targets were lower in the three most recent trials. Summary analyses showed that, compared with conventional control, intensive glucose control reduced the risk of cardiovascular disease (relative risk (RR): 0.90, 95% confidence interval (CI): 0.83, 0.98; risk difference per 1,000 patients per 5 years (RD): -15, CI: -24, -5) but not cardiovascular death (RR: 0.97, CI: 0.76, 1.24; RD: -3, CI: -14, 7) or all-cause mortality (RR: 0.98, CI: 0.84, 1.15; RD: -4, CI: -17, 10) and increased the risk of severe hypoglycemia (RR: 2.03, CI: 1.46, 2.81; RD: 39, CI: 7, 71). Similar to overall analyses, intensive glucose control reduced risk of cardiovascular disease and increased risk of severe hypoglycemia in pooled findings from early and more recent trials. LIMITATIONS: Summary rather than individual data were pooled across trials. CONCLUSIONS: Intensive glucose control reduced risk for some cardiovascular disease (e.g., non-fatal myocardial infarction), but did not reduce risk for cardiovascular or all-cause mortality and increased risk of severe hypoglycemia.