Diabetes drug with little side-effects

Dr. V. Mohan, Director, Madras Diabetes Research Foundation, Chennai, and Dr. Salim Yusuf, Director, Division of Cardiology, and Dr. Hertzel Gerstein, Director, Division of Endocrinology, McMaster University, Hamilton, Canada, write:

This is in response to the news item ``The wonder drug that wasn't (TheHindu, July 5) to set the record straight.

The Diabetes Reduction Assessment with Rosiglitazone and Ramipril Medication (DREAM) is an international study which has undergone extensive peer reviews by several international bodies including the Canadian Institutes for Health Research and other scientists in the U.S., the U.K., Australia, and several European and South American countries. The trial has been approved by the Food and Drug Administration (FDA) in the U.S. and the Health Protection Branch of Health Canada for conduct in these countries. Thus the DREAM study has received extensive scrutiny, review and approval.

Dr. C. V. Krishnaswami of the VHS Medical Centre, Chennai, has unfortunately extrapolated the side-effects of Troglitazone to a different compound that we are using in the trial, namely Rosiglitazone. It is indeed true that Troglitazone was banned due to liver toxicity. But precisely for this reason, Rosiglitazone an Pioglitazone the next generation drugs of this new class of insulin sensitisers have been very carefully and extensively evaluated in clinical trials across the world to ensure their safety and efficacy. Rosiglitazone is now available worldwide and till date there have been no reports of liver toxicity with this drug although several million prescriptions have been dispensed. In India, several drug trials were conducted before the drug was marketed. It has been the experience of diabetologists all over India that many patients whose diabetes could never be controlled well are now maintaining excellent control after addition of this drug. Until now, there has not been any report of liver toxicity due to this drug in India although several thousand patients are using the drug. The only side-effects reported are weight gain and mild swelling of feet in some patients both of which are dose related and reversible if the drug is withdrawn. Rosiglitazone, and the insulin sensitizers in general, address the core defect in diabetes, namely insulin resistance; and hence it makes sound physiological sense to use these drugs early in the course of the disease, namely at the stage of impaired glucose tolerance to try to prevent diabetes. The DREAM study is an attempt in this direction.

Ramipril prevented strokes

Regarding the other drug, Ramipril, Dr. Krishnaswami is right in saying that it is primarily an anti-hypertensive agent and his comments were probably justified before the HOPE trial. But in the light of the landmark HOPE trial which showed that Ramipril actually prevented diabetes (although it was not an expected end- point of that trial), the DREAM study assumes great significance. It is well-known that subjects with impaired glucose tolerance (inability to handle a glucose load appropriately, but no diabetes) are at the same risk of developing cardiovascular complications as subjects with diabetes. In the HOPE study, Ramipril prevented heart attacks, strokes and cardiovascular- related deaths in both diabetics and non-diabetics with previous cardiovascular disease. Thus, irrespective of whether Ramipril prevents diabetes or not, it could definitely be expected to reduce cardiovascular morbidity and mortality in the study particularly since IGT subjects are known to have significantly higher prevalence of hypertension. If the study eventually proves that by using one drug one can prevent diabetes, control BP and reduce cardiovascular morbidity and mortality, it would indeed be a ``DREAM'' come true.

It is a tribute to India that for such a landmark study, Indian diabetologists have also been invited to take part. Whenever a new trial is taken up, it tries to answer unsolved questions and thus improve the lives of patients. Dr. Krishnaswami himself states that 5.5 per cent of IGT developed diabetes every year in his study.

A simple calculation will reveal that this works over to 55 per cent conversion to diabetes over a 10-year period. In fact, several studies now suggest that Indians with IGT probably develop diabetes at a faster rate than other ethnic groups. Given the millions of people at risk of developing diabetes in India, nowhere are prevention studies more relevant than in India.

Needless to say, the study will have to be reviewed and approved by the Ethical Committees of all three institutions participating in the trial and all necessary regulatory permissions will have to be obtained before it is implemented in India. Further, an independent international Data and Safety Monitoring Committee consisting of eminent scientists and physicians will carefully monitor all aspects of the study. This provides a high level of oversight and protection for the participants in the study.

No progress can be made in the field of medicine without trying out newer methods of treatment. In this case, the study does not involve any experimental drugs but is merely an extension of the use of two well-established drugs for a new indication - to try to prevent diabetes itself. If, at the end of the study, we have been able to prevent diabetes and/or prevent cardiovascular morbidity and mortality, we would consider our efforts to have been worthwhile.

Send this article to Friends by E-Mail

Section  : National
Previous : SC directive on payscales of judicial officers
Next     : 'Central relief inadequate'