Background During the United Kingdom Prospective Diabetes Study(UKPDS), patients with type 2 diabetes mellitus who receivedintensive glucose therapy had a lower risk of microvascularcomplications than did those receiving conventional dietarytherapy. We conducted post-trial monitoring to determine whetherthis improved glucose control persisted and whether such therapyhad 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 sulfonylureaor insulin or, in overweight patients, metformin) for glucosecontrol. In post-trial monitoring, 3277 patients were askedto attend annual UKPDS clinics for 5 years, but no attemptswere made to maintain their previously assigned therapies. Annualquestionnaires were used to follow patients who were unableto attend the clinics, and all patients in years 6 to 10 wereassessed through questionnaires. We examined seven prespecifiedaggregate clinical outcomes from the UKPDS on an intention-to-treatbasis, according to previous randomization categories.
Results Between-group differences in glycated hemoglobin levelswere lost after the first year. In the sulfonylurea–insulingroup, relative reductions in risk persisted at 10 years forany diabetes-related end point (9%, P=0.04) and microvasculardisease (24%, P=0.001), and risk reductions for myocardial infarction(15%, P=0.01) and death from any cause (13%, P=0.007) emergedover time, as more events occurred. In the metformin group,significant risk reductions persisted for any diabetes-relatedend 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, acontinued reduction in microvascular risk and emergent riskreductions for myocardial infarction and death from any causewere observed during 10 years of post-trial follow-up. A continuedbenefit after metformin therapy was evident among overweightpatients. (UKPDS 80; Current Controlled Trials number, ISRCTN75451837
[controlled-trials.com]
.)
Source Information
From the Diabetes Trials Unit (R.R.H., S.K.P., M.A.B.), the Division of Public Health and Primary Health Care (H.A.W.N.), and the National Institute of Health Research (NIHR) School for Primary Care Research (H.A.W.N.), Oxford Centre for Diabetes, Endocrinology, and Metabolism (R.R.H., S.K.P., M.A.B., D.R.M., H.A.W.N.); and the NIHR Oxford Biomedical Research Centre (R.R.H., D.R.M., H.A.W.N.) — both in Oxford, United Kingdom. This article (10.1056/NEJMoa0806470) was published at www.nejm.org on September 10, 2008.
Address reprint requests to Dr. Holman at the Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom, or at rury.holman{at}dtu.ox.ac.uk.
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