Meta-analysis supports tight glycemic control for microvascular health
medwireNews: A meta-analysis from the Collaborators on Trials of Lowering Glucose (CONTROL) group supports intensive glycemic control for improved microvascular outcomes in patients with type 2 diabetes.
The analysis, which includes individual patient data from 27,049 adult participants of the ACCORD, ADVANCE, UKPDS, and VADT trials, found a reduced risk for kidney and retinal outcomes, but not for neuropathy, during a median 5 years of follow-up.
However, Sophia Zoungas (The George Institute for Global Health, University of Sydney, New South Wales, Australia) and study co-authors note that there was marked variability between the trials for neuropathic outcomes, which “were assessed with subjective and variable methods such as monofilament and reflex testing.”
They suggest: “The findings might have differed if standardised nerve conduction testing had been applied in all four trials.”
During follow-up, the trials’ participants experienced a total of 1626 kidney events, and the risk for this outcome was a significant 20% lower for participants who had been randomly assigned to receive intensive glycemic control than for those who received standard treatment.
There were also 795 eye events, and intensive glycemic control reduced this risk by a significant 13%, but the risk for nerve events, of which there were 7598, was not influenced by treatment intensity.
The effects of intensive glucose control on microvascular outcomes were consistent across most prespecified subgroups including for age, ethnicity, diabetes duration, and glycated hemoglobin (HbA1c) level. The exception was that men appeared to derive more benefit than women from intensive treatment specifically for retinal outcomes, although the researchers caution that it was an exploratory analysis and that the large number of analyses increases the likelihood of the finding being a statistical anomaly.
The findings are published in The Lancet Diabetes & Endocrinology, along with a linked commentary, in which William Herrington and David Preiss, both from the University of Oxford, UK, describe the effect of tight glycemic control as “important, but modest.”
Factoring in the CONTROL group’s previous macrovascular outcomes meta-analysis, they calculate that the number of severe hypoglycemic events caused by tight glycemic control is about double the combined number of macro- and microvascular events prevented.
This supports the “cautious” American Diabetes Association advice to consider HbA1c targets below 6.5% only if they can be achieved without significant hypoglycemia, they say.
However, the commentators also note the potential for a “legacy effect” of tight glycemic control whereby its benefits continue to accumulate after it has been discontinued, which could influence the risk–benefit balance. Some long-term studies have shown such an effect, whereas others have not.
Therefore, “extension of the meta-analysis to the post-trial period is required for a complete assessment of risks versus benefits of this treatment strategy,” they conclude.
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