UKPDS
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group
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Overview
In newly diagnosed T2DM, intensive glycemic control reduced microvascular complications, with less immediate effect on macrovascular outcomes.
Clinical takeaway
UKPDS established that glycemic control matters in T2DM, especially for microvascular disease, and shaped early diabetes management targets.
Key result
Intensive control lowered any diabetes-related endpoint by 12% (RR 0.88), driven by a 25% cut in microvascular endpoints (RR 0.75); diabetes-related death and all-cause mortality did not differ.
Practice impact
Supports early glycemic control to prevent microvascular complications.
Evidence
Study design
Randomized controlled trial.
Enrollment
3,867
Follow-up
Median 10 years.
Geography
United Kingdom
Clinical question
Does intensive glucose control reduce diabetes complications in newly diagnosed type 2 diabetes?
Population
- Patients with newly diagnosed type 2 diabetes.
Intervention
Intensive glucose control using a sulfonylurea or insulin.
Comparator
Conventional therapy (diet first, drugs if needed).
Primary outcome
Three aggregate endpoints: any diabetes-related endpoint, diabetes-related death, and all-cause mortality.
Intensive glycemic control lowered any diabetes-related endpoint by 12%, mostly through a 25% reduction in microvascular endpoints; macrovascular disease was not reduced during the trial.
Relative risk / 0.88 / 95% CI 0.79-0.99 / p=0.029
Key results
- Median HbA1c was 7.0% with intensive therapy vs 7.9% with conventional therapy.
- Any diabetes-related endpoint: RR 0.88 (95% CI 0.79-0.99; p=0.029), a 12% reduction.
- Diabetes-related death: 10% lower, not significant (95% CI -11% to 27%; p=0.34). All-cause mortality: 6% lower, not significant (95% CI -10% to 20%; p=0.44).
- Microvascular endpoints: RR 0.75 (95% CI 0.60-0.93; p=0.0099), a 25% reduction driven by less retinal photocoagulation.
- Myocardial infarction was reduced by 16% but did not reach significance (p=0.052) during the main trial.
Harms
- Hypoglycemia and weight gain were more common with intensive therapy.
- Hypoglycemia rates were highest with insulin.
Clinical Use
Practice impact
- Supports early glycemic control to prevent microvascular complications.
Applicability
- Most applicable to patients with newly diagnosed type 2 diabetes considered for early glycemic control.
Limitations
- Older medication era predating GLP-1 and SGLT2 cardiometabolic therapies.
- The clearest benefit during the main trial was microvascular, not macrovascular.
- Interpreting cardiovascular benefit requires the 10-year post-trial follow-up.
Common misinterpretations
- The macrovascular (MI) benefit largely emerged in post-trial follow-up as a legacy effect, not during the main trial.
- UKPDS 34 separately showed metformin reduced mortality in overweight patients, a different substudy from this sulfonylurea/insulin comparison.
Citation
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837-853.
Intensive blood-glucose control by either sulphonylureas or insulin substantially decreases the risk of microvascular complications, but not macrovascular disease, in patients with type 2 diabetes.
- PMID
- 9742976