J-DOIT3 supports intensive management to prevent diabetic complications
medwireNews: The J-DIOT3 trial results support the findings from Steno-2, showing that intensive risk factor management can reduce the risk for complications in patients with type 2 diabetes.
As noted by commentator Per-Henrik Groop (University of Helsinki, Finland), Steno-2 is relatively old, having been published in 2003, and is quite small, with only 160 patients, yet is the only randomized controlled trial demonstrating the benefits of intensive risk factor management in diabetes patients.
“[Steno-2] probably has the world record in terms of citation per patient,” he told delegates at the EASD annual meeting in Lisbon, Portugal.
J-DOIT3 was much larger, with 1271 diabetes patients with hypertension or dyslipidemia assigned to receive conventional treatment and 1269 assigned to intensive treatment of blood glucose, blood pressure, and cholesterol. Yet the trial just missed its primary endpoint; the risk for the primary outcome of myocardial infarction, stroke, revascularization, and death was reduced by a nonsignificant 19% in the intensive versus conventional treatment groups, with a 95% confidence interval of 0.63 to 1.04 and a p value of 0.094.
However, there were some imbalances between the randomized groups, such as a higher rate of smoking in the intensive group, and when the researchers adjusted for these, the hazard ratio decreased to 0.76 and became statistically significant.
Nevertheless, Groop said the trial has produced “clinically meaningful data,” despite not achieving its endpoint “in the strictest statistical sense.” He attributed the missed endpoint to the good control of risk factors in the conventional treatment group, noting that by aiming at the strict Japanese guideline targets “the trialists made life difficult for themselves.”
As a result of this rigorous treatment, the trial accumulated endpoint events very slowly, requiring the investigators to expand the components of the primary endpoint, reduce the statistical power, and increase the length of follow-up.
Neither group actually met these tough targets, with the exception of diastolic blood pressure, but they achieved low levels of glycated hemoglobin, blood pressure, and cholesterol overall. For example, the conventional and intensive groups achieved glycated hemoglobin levels of 7.2% and 6.8%, respectively (the target levels were 6.9 and 6.2%).
And the intensive group achieved significantly lower levels of all three risk factors than the conventional group.
Of note, patients in the intensive treatment group had a highly significant 58% reduction in the risk for cerebrovascular events – primarily strokes, which are more common than myocardial infarctions in Japanese populations. Takashi Kadowaki (University of Tokyo Hospital, Japan), who presented the results, attributed this to the intensive blood pressure control, and suggested that Japanese diabetes patients may benefit from a lower blood pressure target than currently advocated.
The risk for coronary events, by contrast, was reduced by a nonsignificant 14%. There was also a significant 32% reduction in the risk for nephropathy and a significant 14% reduction in the risk for retinopathy, although the risk for lower-limb vascular events was unaffected.
These risk reductions came with an increased risk for hypoglycemia, which occurred in 41.1% versus 22.3% of the intensive and conventional treatment groups, respectively. Severe hypoglycemia was extremely rare.
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