The UK Prospective Diabetes Study (UKPDS) was a landmark randomised, multicentre trial of glycaemic therapies in 5,102 patients with newly diagnosed type 2 diabetes. It ran for twenty years (1977 to 1997) in 23 UK clinical sites and showed conclusively that the complications of type 2 diabetes, previously often regarded as inevitable, could be reduced by improving blood glucose and/or blood pressure control.
The UKPDS was designed and run by the late Professor Robert Turner and Professor Rury Holman.
Reducing glucose exposure (HbA1c 7.0 % versus 7.9 % over median 10.0 years), with sulphonylurea or insulin therapy, reduced the risk of “any diabetes-related endpoint” by 12% and microvascular disease by 25%, with a 16% trend to a reduced risk of myocardial infarction (P=0.052). Post-UGDP (University Group Diabetes Program) fears that sulphonylurea or insulin therapies may be harmful were allayed, as no increase was observed with these agents in the incidence of cardiovascular deaths, myocardial infarction or sudden death. Although neither of these therapies impaired quality of life, both increased risk of hypoglycaemia and weight gain.
In an embedded study of 1,148 hypertensive patients, improving blood pressure (142/82 mmHg versus 154/87 mmHg over median 8.4 years) with an ACE inhibitor or a beta blocker, reduced the risk of both microvascular and macrovascular disease. A cost-effectiveness analysis showed that cost savings from the reduction in diabetic complications outweighed the cost of the additional medication required, but not the extra staff costs involved.
Principal investigator:Rury Holman
Sponsor:Medical Research Council (1997-2002)
Oxford University (2002-2007)
Reference number:ISRCTN75451837
When the intervention trial finished in September 1997, all surviving UKPDS patients were entered into a ten-year, post-trial monitoring programme. This was completed in December 2007 with the results to be presented at the September 2008 EASD meeting.
The UKPDS Post-Trial monitoring results showed continuing benefit of earlier improved glucose control, with maintenance of the relative risk reductions reported in 1998 for any diabetes related endpoint (9%, P=0.04) and microvascular disease (24%, P=0.001), despite loss of within trial blood glucose and antihyperglycaemic therapy differences – a legacy effect.
In addition, significant relative risk reductions emerged for myocardial infarction (15%, P=0.014) and all-cause mortality (12%, P=0.007).
The UKPDS Post-Trial monitoring results showed continuing benefit of earlier metformin therapy, with maintenance of the relative risk reductions reported in 1998 for any diabetes related endpoint (21%, P=0.013), myocardial infarction (33%, P=0.005) and all-cause mortality (27%, P=0.002), despite loss of within trial blood glucose and antihyperglycaemic therapy differences – a legacy effect. No significant changes were seen during or after the trial with respect to microvascular disease.
See: UKPDS 80, N Eng J Med 2008; 359 Holman et al
Download UKPDS 80 slide set here
The UKPDS Post-Trial monitoring results showed that the risk reductions reported in 1998 for any diabetes related endpoint and for microvascular disease were not maintained following the loss of within trial blood pressure and antihypertensive therapy differences. No significant changes were seen during or after the trial with respect to myocardial infarction or all-cause mortality.
See: UKPDS 81, N Eng J Med 2008; 359 Holman et al
Download UKPDS 81 slide set here
In a wide-ranging interview Professors Rury Holman and Amanda Adler discuss the origins of the UKPDS, review the trial findings, the discovery of the post-trial glycaemic and metformin legacy effects, and reveal some of the 44-year follow-up results.
[Watch interview]
The 44-year UK Prospective Diabetes Study (UKPDS) follow-up results were presented today at the 58th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Stockholm, Sweden. The new data from the UKPDS, one of the longest ever studies of diabetes, show that the problems experienced by people with type 2 diabetes, including heart attacks, kidney failure and vision loss are not inevitable, with the benefits of early good blood glucose control persisting for decades....
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Computer simulation models, such as the UKPDS Outcomes model 2 (UKPDS-OM2), allow users to predict disease progression, health outcomes and costs in individuals with type 2 diabetes.
Data from 5,102 UKPDS participants from the 20-year trial and 4,031 survivors with 10 years post-trial follow-up were used to derive time path equations for 13 clinical risk factors: HbA1c, systolic blood pressure, LDL-cholesterol, HDL-cholesterol, BMI, micro- or macro-albuminuria, creatinine, heart rate, white blood cell count, haemoglobin, eGFR, atrial fibrillation and peripheral vascular disease....