10-year follow-up of intensive glucose control in type 2 diabetes.
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.)
Holman
Rury R
RR
Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology, and Metabolism, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom. rury.holman@dtu.ox.ac.uk
Paul
Sanjoy K
SK
Bethel
M Angelyn
MA
Matthews
David R
DR
Neil
H Andrew W
HA
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D012306:Risk; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D013453:Sulfonylurea Compounds