alexa 10-year follow-up of intensive glucose control in type 2 diabetes.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular and Genetic Medicine

Author(s): Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA

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Abstract BACKGROUND: During the United Kingdom Prospective Diabetes Study (UKPDS), patients with type 2 diabetes mellitus who received intensive glucose therapy had a lower risk of microvascular complications than did those receiving conventional dietary therapy. We conducted post-trial monitoring to determine whether this improved glucose control persisted and whether such therapy had a long-term effect on macrovascular outcomes. METHODS: Of 5102 patients with newly diagnosed type 2 diabetes, 4209 were randomly assigned to receive either conventional therapy (dietary restriction) or intensive therapy (either sulfonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires. We examined seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories. RESULTS: Between-group differences in glycated hemoglobin levels were lost after the first year. In the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9\%, P=0.04) and microvascular disease (24\%, P=0.001), and risk reductions for myocardial infarction (15\%, P=0.01) and death from any cause (13\%, P=0.007) emerged over time, as more events occurred. In the metformin group, significant risk reductions 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). CONCLUSIONS: 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 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients. (UKPDS 80; Current Controlled Trials number, ISRCTN75451837.) 2008 Massachusetts Medical Society This article was published in N Engl J Med and referenced in Journal of Molecular and Genetic Medicine

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