Right way, wrong samples

What doctors in India say about the ACCORD study on diabetics, which had to be stopped midway after the death of some patients.

The failure of the intensive treatment arm of ACCORD Action to Control Cardiovascular Risk in Diabetes, a study funded by the US National Institutes of Health, has raised several questions about the age-old belief that maintaining a low blood sugar is the best a diabetic patient can do.

The study, which was to be completed in 2009, had to be stopped midway after a preliminary analysis revealed that patients given intensive treatment to lower their blood sugar were more likely to die than those given less intense treatment.

Accord had enrolled 10,251 participants, of whom, 257 in the intensive treatment group have died, compared with 203 in the standard treatment group. The difference of 54 deaths, or 3 per 1,000 participants each year, over almost four years paints a grim picture. While the international medical fraternity is still awaiting more reports, the Indian doctors are looking into the possible reasons that led to the failure of the study.

8226; Idea behind the study

The ACCORD study was designed to test the effects of intensive control of blood sugar along with aggressive control of blood pressure and lipids.

8226; What went wrong?

According to experts here who were avidly following the research, the very target sample 8211; with people over 60 years in age who had some history of cardiac disorders, led to its failure. The doctors insist that the HBA1C level level of glucose in blood, measured by the percentage of haemoglobin that has glucose stuck to it, ideally maintained at 7 per cent, should not be allowed to drop below 6.5 per cent. But in case of some patients here, it was brought to 6 per cent. The very diagnosis of diabetes implies that 50 per cent of insulin in the body is ineffective, explains Dr Ashok Jhingan, chairman, Delhi Diabetes Research Centre. Also those above 60 are already a prey to one or the other cognitive disorder. 8220;Adoption of intensive measures like usage of insulin pumps and sugar-control pills, in such cases, led to further complications like hypoglycemia. A younger group of sample patients would have led to an interesting insight,8221; Dr Jhingan says.

8226; Should one go for the new researches?

While the well-established hypothesis of controlling diabetes is still debated, trickling in of more researches and insights further add to the dilemma.

The Steno-2 study, published on the same day in the New England Journal of Medicine, for instance, states that in high-risk type 2 diabetes patients, early intensive intervention with multiple drug combinations and behaviour modification, leads to reduced rates of death and cardiovascular disorders.

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While the results of Steno-2 at first glance appear to be in direct contrast to those of ACCORD, experts insist that the study populations of the two trials should not be confused.

8220;Patients in Steno-2 were younger and had been diabetic for an average of six years and just 25 per cent of Steno-2 patients had known cardiovascular disease on entry. Also, because of treatment resistance, only 18 per cent of patients in Steno-2 achieved the target HBA1c level of below 6.5 per cent,8221; says Dr Anoop Mishra, Director and HoD, Diabetes and Metabolic Diseases, Fortis Hospital.

Adds Dr SK Wangnoo, senior consultant endocrinologist, Apollo Hospitals: 8220;One has to understand that most of these studies are driven by pharma-clinical trials. And a single study should never prompt the patient to alter the ongoing course of medication, as the treatment is purely individualistic.8221;

8226; Is there a new remedy ahead?

Today most therapies are being developed with an aim to preserve the beta-cell insulin. Though data about the success rate of a new drug called Byetta is limited, it is believed to considerably supplement the GLP1 molecules, responsible for stimulating insulin production in the body.

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8220;An Incretin Mimetic, when injected, it improves blood sugar control by lowering both post-meal and fasting glucose levels leading to better long-term control as measured by HBA1C,8221; says Dr Wangnoo. Now available in India, it costs Rs 8,000 per month and is usually prescribed in extreme cases.

While insulin inhalers have been withdrawn from market, another non-invasive remedy, expected to hit the Indian shores by mid-May, is the

Incretin enhancer, to be launched under the brand name Januvia. 8220;It will enhance the GLP1 production internally,8221; he adds.

8226; So what is the way forward?

Altering lifestyle is deemed to be the key to tackle diabetes. 8220;Diet control is a must for all diabetics. The aim of controlling blood sugar is to maintain it close to normal through proper medical intervention, while keeping the HBA1C level at 7 per cent,8221; says Dr Vijay Panikar, Senior Diabetologist, Lilawati Hospital, Mumbai.