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.