David Brill
Intensive glucose control, starting early, reduces the long-term risk of death for type 2 diabetics, according to important new follow-up data from the UK Prospective Diabetes Study (UKPDS).
Ten years on from the trial’s conclusion, a 13 percent reduction in all-cause mortality risk and a 15 percent reduction in myocardial infarction risk has emerged among the intensively-controlled patients (P=0.007 and 0.01, respectively). These benefits – termed a “legacy effect” – were seen even though differences in glycated hemoglobin levels between the groups disappeared just 1 year after withdrawal of the randomized intervention.
The original study ran from 1977 to 1997. Surviving patients were then returned to their usual care but continued to be followed up with annual clinic visits for 5 years and questionnaires for a further 5 years.
A risk reduction for microvascular disease – first reported at the end of the trial – also persisted 10 years later for the intensively-controlled patients.
“What this is saying to me is that you can’t wait to treat diabetes,” Professor Rury Holman, lead investigator for the UKPDS, told a press conference at the 44th Annual Meeting of the European Association for the Study of Diabetes (EASD), held recently in Rome, Italy.
“You need to treat it early – at least from diagnosis – and you will get additional benefits in the long term, rather than just waiting until the blood glucose is high or, heaven forbid, they’ve had a complication and then suddenly getting interested in
treating them.”
The same legacy effects were not seen, however, for tight control of blood pressure in hypertensive type 2 diabetics. Risk reductions for diabetes-related death, stroke
and microvascular disease were reported in 1998 but these benefits disappeared within 2 years of the end of the intervention period.
“This doesn’t mean that blood pressure is not important,” said Holman, head of the Diabetes Trials Unit at The Oxford Centre for Diabetes, Endocrinology and Metabolism,
UK.
“We take this to mean that the full benefits of blood pressure control in the tight control group had emerged by trial end, and over the post-study period there is no additional benefit over and above that recorded in the trial.”
The new post-trial data from UKPDS were presented at the EASD conference and subsequently published online in two separate papers in The New England Journal of Medicine.
The original study involved 5,102 newlydiagnosed diabetics, 4,209 of whom were randomized to receive intensive or regular glucose control. [Lancet 1998;352:837-53] A total of 3,277 patients entered post-trial monitoring.
The blood pressure control arm of the study included 1,148 patients, 884 of whom entered post-trial monitoring. The original intervention regimen comprised up to 100 mg atenolol once daily or up to 50 mg captopril twice daily. [BMJ 1998;317:703-13]
Intensive glucose control in the UKPDS was carried out with insulin or sulfonylurea, or metformin for overweight patients. The target was to maintain a fasting plasma glucose level below 6 mmol/L.
A significant risk reduction for any diabetes-related endpoint was reported at conclusion of the trial, driven largely by the reduction in microvascular risk, but the results for all-cause mortality and myocardial infarction did not reach significance at the time.
The benefits of metformin among overweight patients were considerable, with risk reductions of 32 percent for any diabetes-related endpoint and 42 percent for diabetes-related death, reported in 1998. [Lancet 1998;352:854-65] These effects were attenuated in the 2008 data but nonetheless persisted, with significant risk reductions of 21 percent and 30 percent, respectively.
“When we started the study people didn’t believe that treating glucose was important. Many people thought that complications were genetically determined and that glucose was not relevant,” added Holman.
“After UKPDS showed you have to control glucose or you’ll get complications, everybody got into the game and started giving two, three or four treatments. Here I believe we are seeing the impact of that in clinical practice.”
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