Cardiovascular disease is prevented over the long term by better blood glucose control
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Cardiovascular Disease is Prevented Over the Long Term by Better Blood Glucose Control Holman RR, Paul SK, Bethel MA, et al.: 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008, 359:1577–1589.
tions persisted for any diabetes-related end point (21%; P = 0.01), myocardial infarction (33%; P = 0.005), and death from any cause (27%; P = 0.002).
Rating: ••Of major importance.
Discussion: Despite an early loss of glycemic differences, a continued reduction in microvascular risk and emergent risk reductions for myocardial infarction and death from any cause were observed during the decade-long followup. A continued benefit after metformin therapy was evident in overweight patients.
Introduction: The United Kingdom Prospective Diabetes Study (UKPDS) was a randomized, prospective, multicenter trial comparing intensive glucose control with conventional therapy in people with newly diagnosed type 2 diabetes mellitus. UKPDS is now an outcomes study with up to 10 years of follow-up. During the randomized trial phase, study participants achieved an average mean difference in glycated hemoglobin of 0.9% [1]. Intensive treatment was associated with a reduced risk of microvascular complications and a nonsignificant (P = 0.052) reduction in the relative risk of myocardial infarction. Aims: This article reports outcomes of 10-year posttrial observational monitoring. Methods: Of 5102 patients with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive conventional therapy (dietary restriction) or intensive therapy (sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. During the fi rst 5 years of monitoring, 3277 patients were asked to attend annual UKPDS clinics. No attempts were made to maintain their previously assigned therapies. Patients unable to attend the clinics were sent questionnaires. During the sixth through 10th years of monitoring, all patients were assessed through the use of questionnaires. The authors reported results for seven prespecified aggregate clinical outcomes from UKPDS on an intention-to-treat basis, according to previous randomization categories. Results: Between-group differences in glycated hemoglobin levels were lost after the fi rst year. For those treated with sulfonylurea or insulin, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%; P = 0.04; absolute risk reduction [ARR], 4.1%; number needed to treat [NNT], 24) and microvascular disease (24%; P = 0.001; ARR, 3.2%; NNT, 31). Risk reductions for myocardial infarction (15%; P = 0.01; ARR, 2.8%; NNT, 36) and death from any cause (13%; P = 0.007; ARR, 3.5%; NNT, 29) emerged over time as more events occurred. In the metformin group, significant risk reduc-
Editors’ comments The year 2008 was a big year for reporting results of major clinical trials in type 2 diabetes and cardiovascular disease (CVD). The new long-term follow-up from UKPDS is the most paradigm-shifting study, taking the glucose hypothesis “into the end zone.” UKPDS
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