Tanika N. Kelly, PhD; Lydia A. Bazzano, MD, PhD; Vivian A. Fonseca, MD; Tina K. Thethi, MD; Kristi Reynolds, PhD; Jiang He, MD, PhD
Kelly TN, Bazzano LA, Fonseca VA, Thethi TK, Reynolds K, He J. Systematic Review: Glucose Control and Cardiovascular Disease in Type 2 Diabetes. Ann Intern Med. 2009;151:394-403. doi: 10.7326/0003-4819-151-6-200909150-00137
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Published: Ann Intern Med. 2009;151(6):394-403.
Results from clinical trials examining the effect of intensive glucose control on cardiovascular disease have been conflicting.
To summarize clinical benefits and harms of intensive versus conventional glucose control for adults with type 2 diabetes.
Studies were retrieved by systematically searching the MEDLINE database (January 1950 to April 2009) with no language restrictions.
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.
Two investigators independently abstracted data on study variables and outcomes, including severe hypoglycemia, cardiovascular disease, and all-cause mortality.
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], âˆ’15 [CI, âˆ’24 to âˆ’5]) but not cardiovascular death (RR, 0.97 [CI, 0.76 to 1.24]; RD, âˆ’3 [CI, âˆ’14 to 7]) or all-cause mortality (RR, 0.98 [CI, 0.84 to 1.15]; RD, âˆ’4 [CI, âˆ’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.
Summary rather than individual data were pooled across trials.
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 all-cause mortality, and increased the risk for severe hypoglycemia.
The relative benefits and harms of intensive versus conventional glucose control for type 2 diabetes are controversial.
This review of 5 large trials found that, compared with conventional control, intensive glucose control reduced the risk for cardiovascular disease (mostly nonfatal myocardial infarction) but not for cardiovascular death or all-cause mortality, and increased risk for severe hypoglycemia. Trial design, achieved control, and findings were heterogeneous: Early trials suggested possible decreased risk for death with intensive control, whereas some more recent trials suggested possible increased risk for death with more stringent control.
The investigators did not evaluate costs. They pooled summary findings from trials rather than individual data from patients.
Appendix Table 1.
Appendix Table 2.
ACCORD = Action to Control Cardiovascular Risk in Diabetes (12); ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (13); UKPDS = United Kingdom Prospective Diabetes Study (8, 11); VADT = Veterans Affairs Diabetes Trial (14).
MI = myocardial infarction; PAD = peripheral artery disease.
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Cardiology, Endocrine and Metabolism, Diabetes, Coronary Risk Factors.
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