Diabetes Can Be Prevented With Drug Therapy, Study Shows

Rosiglitazone reduced the chance of getting diabetes by 60 per cent among those taking part in the three-year, international trial that involved 191 clinics in 21 countries.

Results of the trial known as DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone medication) were presented today in Copenhagen, at the 42nd Annual Meeting of the European Association for the Study of Diabetes.

Dr. Hertzel Gerstein, co-principal investigator and a professor of medicine at McMaster, said the results have major implications for future health care.

"If we can prevent diabetes, we may also be able to prevent the serious cardiovascular, eye, kidney, and other health consequences of diabetes," said Gerstein, an endocrinologist. "The DREAM results show that adding rosiglitazone to healthy lifestyle advice substantially lowers the chance of getting diabetes in people at high risk for the disease."

The DREAM trial was designed to answer the question: "Does ramipril 15 mg/day and/or rosiglitazone 8 mg/day prevent type 2 diabetes?" The study included 5,269 people worldwide whose average age was 55 and whose glucose level was starting to rise but who did not have diabetes (i.e. they had impaired fasting glucose or impaired glucose tolerance). Participants took one of the medications or a placebo over a period of three years.

Ramipril is an angiotensin-converting enzyme inhibitor (ACE-I) drug that was shown to prevent cardiovascular events in high-risk people, including those with diabetes, in the Heart Outcomes Prevention Evaluation (HOPE) study. That study suggested that it may also prevent diabetes.

Rosiglitazone is a thiazolidinedione (TZD) drug that is currently used to treat diabetes. It works by helping the body respond to its own insulin and may also preserve the ability to make insulin.

Among study participants taking rosiglitazone, only 12 per cent developed diabetes, compared to 26 per cent who were taking the placebo. Rosiglitazone also normalized glucose levels in 51 per cent of participants versus 30 per cent of those taking a placebo. It benefited all participants, and particularly those who were the heaviest.

"The world is facing a major diabetes epidemic," said Professor Rury Holman, European co-chair of DREAM and Professor of Diabetic Medicine, University of Oxford, UK. "The knowledge that rosiglitazone can reduce the risk of people developing diabetes provides another opportunity to help tackle this growing health care problem."

Ramipril did not reduce the risk of diabetes, which affected 18 per cent of participants on that drug and 20 per cent on placebo. However, significantly more people taking ramipril (43 per cent) than placebo (38 per cent) had normal glucose levels by the end of the study, which could also have future implications.

"Diabetes dramatically increases the risk of cardiovascular and other problems," said Dr. Salim Yusuf, cardiologist and DREAM co-principal investigator. "Although ramipril did not prevent diabetes, the beneficial metabolic effects that we found may add to the clinical benefits of ACE-I seen in HOPE and other studies."

More than five per cent of all adults have a diagnosis of type 2 diabetes, and this rate is rising rapidly throughout the world, due in part to the increase in weight and reduction in physical activity in both developed and developing countries.

"The results of both the HOPE and DREAM studies offer us new strategies for preventing and delaying the onset of diabetes and its devastating complications," said Dr. Diane Finegood, Scientific Director of CIHR s Institute of Nutrition, Metabolism and Diabetes.

"With an estimated one in three people born in the year 2000 likely to develop diabetes in their lifetime, we need to do all we can to identify effective treatment and prevention strategies. With funding from CIHR, Drs. Gerstein and Yusuf were able to lead this important multi-national effort requiring the co-operation of investigators and their staff at 191 sites in North and South America, Europe, India and Australia."

Those with type 2 diabetes require life long therapy to reduce their high risk of further complications such as blindness, kidney failure, amputations, heart attacks, strokes and premature death.

Although modest dietary and physical activity changes can clearly prevent diabetes in many people, additional strategies for high risk individuals are also urgently needed.

The results of the DREAM trial are also being published in the New England Journal of Medicine and The Lancet.

DREAM was funded by the Canadian Institutes of Health Research via the CIHR/Rx&D Collaborative Research Program, Sanofi-Aventis and King Pharmaceuticals (manufacturers of ramipril) as well as GlaxoSmithKline (manufacturer of rosiglitazone).

It was led by an independent international steering committee and conducted by the Population Health Research Institute at the Michael G. DeGroote School of Medicine at McMaster University and Hamilton Health Sciences in Hamilton, Ontario, Canada.