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Ten-year UKPDS data confirm benefits of early, intensive glucose control
Glycemic effects and metformin therapy, not tight BP control, are associated with reductions in MI and all–cause mortality.
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44th Annual Meeting of the EASD
ROME — Early intervention with intensive glucose control has long-lasting effects, according to 10-year follow-up data on a cohort of patients with type 2 diabetes enrolled in the United Kingdom Prospective Diabetes Study.
Researchers from the United Kingdom conducted post-trial monitoring of a subset of 5,102 patients enrolled in the UKPDS, a randomized, prospective, multicenter trial that ran from 1977 and closed in 1997. Results from the original UKPDS showed a reduced risk for microvascular complications, but no improvement in MI or all-cause mortality among patients assigned to intensive glucose-lowering using a sulfonylurea or insulin. A reduced risk for MI and all-cause mortality but not microvascular complications was seen in those assigned to metformin.
Now, 10 years later, follow-up data from the trial demonstrate that early intensive glucose control not only continued to reduce microvascular complications, but also reduced risk for MI and all-cause mortality. The benefits of earlier metformin therapy were sustained as well. However, the benefits of tight BP control reported before the trial was terminated were not maintained over time.
“Diabetes is a disease for a lifetime. Our question was when we stopped intervening would the impact we’d seen disappear or would there be a continuing benefit, what we call a legacy effect,” Rury R. Holman, MBCHB, FRCP, professor of diabetic medicine at the University of Oxford in the United Kingdom, told Endocrine Today.
These post-monitoring data were presented at the 44th Annual Meeting of the European Association for the Study of Diabetes and were published simultaneously online in the New England Journal of Medicine.
Legacy effect
In the original UKPDS, researchers randomly assigned 4,209 patients to either conventional therapy in the form of dietary restriction or intensive therapy with sulfonylurea, insulin or, in overweight patients only, metformin. For post-trial monitoring, Holman and colleagues asked 3,277 patients to attend UKPDS clinics for five years and complete questionnaires through year 10. Of note, patients were not asked to maintain their previously assigned therapies.
Between-group differences in glycemic control were lost in the first year after the trial closed. At 10 years, patients assigned to intensive control with sulfonylurea and insulin had reduced risk for microvascular disease (24%), MI (15%), death from any cause (13%) and any diabetes-related end point (9%) compared with patients assigned to conventional therapy. Patients assigned to metformin experienced significant risk reductions for MI (33%), death from any cause (27%) and any diabetes-related end point (21%) that persisted over time compared with controls.
“We are seeing a continued benefit of earlier intervention. The message is very clear — early intensive glucose control leads to increased benefits over time, and waiting and treating later leads to disappointing results,” he said. “I think we will now see an emphasis on keeping blood glucose normal from day one, rather than trying to rescue it from some high value later on.”
Tight BP-lowering
The researchers also evaluated 1,148 patients with hypertension assigned to tight BP control with ACE inhibitors and beta blockers compared with conventional control over a median of 8.4 years. They asked 884 patients to undergo post-trial monitoring — similar to the glycemic arm — through UKPDS clinics and questionnaires. Again, no attempt was made to maintain their previously assigned therapies. David R. Matthews, DPhil, BM, BCh, FRCP, professor of diabetic medicine at the University of Oxford, presented these post trial monitoring study results.
The results suggested that patients assigned to tight BP-lowering (n=592) experienced significant reductions in microvascular disease, stroke and diabetes-related death, but no significant benefit in terms of MI risk or all-cause mortality. Like the glycemic arm, between-group differences in BP disappeared within two years after the UKPDS closed. The researchers reported no risk reductions for MI or death from any cause among patients assigned to tight BP control, but a significant risk reduction for peripheral vascular disease.
They concluded that improvement in BP control early-on in patients with type 2 diabetes and hypertension was associated with a reduced risk of complications, according to Matthews. However, BP control must be continued for the benefits to be maintained.
“With glucose control it matters how well you are treated now and how well you were treated in the past; with blood pressure, it seems to be related just to current therapy, confirming how essential it is to maintain good blood-pressure levels over time if the risk of complications is to be minimized,” he said in a press statement. – by Katie Kalvaitis
Relative Risk Reduction Among Patients Randomly Assigned to Intensive Glucose Control with Sulfonylurea/Insulin: |
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Relative Risk Reduction Among Patients Randomly Assigned to Tight Blood Pressure Control: |
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For more information:
- Matthews DR, Holman R. UKPDS 30 year data – are there legacy effects of improved glucose and blood pressure control? Presented at: the 44th Annual Meeting of the EASD; Rome; Sept. 7-11, 2008.
- N Engl J Med. 2008;doi:10.1056/NEJMoa0806470.
- N Engl J Med. 2008;doi:10.1056/NEJMoa0806359.