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.
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.
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).
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