Glycemic Control in Diabetes: A Tale of Three Studies

Abstract

Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VACSDM); both studies showed A1C 7.1% in the treatment group and 9.3- 9.4% in the control group. Analysis of a number of observational studies suggests that for every 1% increase in A1C, there is an 18% increase in the risk of CVD. The ACCORDstudywasbasedonthehypoth- esis that a 1.5% difference in A1C would result in a 15% difference in event rates in apopulationofhigh-riskdiabeticindivid- uals having a 3% annual CVD event rate. Power calculations required a sample size of 10,000 individuals, with 10,251 actu- ally participating and 5,128 randomized to intensive and 5,123 to standard glyce- mia goals. In addition, half of the partici- pantswererandomizedtointensiveblood pressure lowering to a systolic goal 120 mmHg (2,362 individuals) vs. 140 mmHg (2,371 individuals), and half were randomized to statin plus fibrate (2,753 individuals)vs.statinplusplacebo(2,765 individuals). Eligibility required stable type 2 diabetes treatment for at least 3 months with A1C 7.5-9.0%, BMI 45 kg/m2, creatinine 1.5 mg/dl, and age 40-79 years with, or 55-79 years with- out, established CVD—the latter group either having other anatomic evidence of atherosclerosis, albuminuria, left ventric- ularhypertrophy,oratleasttwoCVDrisk factors. The primary outcome wasfirst occur- rence of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death, and secondary outcomes included the above individual outcomes, total mortal- ity, quality of life, cost, cognitive health, skeletal health, and microvascular out- comes. At baseline, the groups were well matched, with median age 62 years, dia- betes duration 10 years, just over one- third of the subjects with a prior CVD event, mean BMI 32 kg/m2, blood pres- sure 136/75 mmHg, A1C 8.3%, and LDL