|Dr. J. R. Conway of the Diabetes Clinic, 155 Elmsley St. in Smiths Falls is an investigator in the largest Diabetes Prevention study ever undertaken in the world. NAVIGATOR study to determine benefit of early administration of Starlix® and Diovan® in people with impaired glucose tolerance who have high cardiovascular risk
Basel, 10 September 2001 - Novartis today announced the launch of NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research), the largest-ever diabetes prevention clinical trial to date, which aims to determine whether long-term administration of Starlix® (nateglinide) or Diovan® (valsartan) reduce or delay the development of type 2 diabetes and cardiovascular (CV) disease in people who have impaired glucose tolerance (IGT) and are at high cardiovascular risk. Recent studies suggest that people with IGT are 34% more likely to die from CV disease than people with normal blood glucose control.
IGT is an intermediate state between normal blood glucose control and type 2 diabetes. IGT is characterized by an excessive rise in blood glucose following consumption of 75g glucose. People with IGT show abnormalities in both insulin secretion and response to insulin (insulin sensitivity), and are at high risk of progressing to type 2 diabetes, with a 40-50% chance of developing the disease within ten years. IGT is also a major risk factor for CV disease.
"With as many as one in seven people over 40 being affected by IGT, it is essential that we evaluate strategies to improve the outlook of people with this condition. We believe that collaborative research in these two fields will ultimately lead to treatment strategies that can prevent type 2 diabetes and cardiovascular disease in high-risk populations," said Thomas Ebeling, Chief Executive Officer, Novartis Pharma AG.)
Speaking at the launch of the NAVIGATOR trial, Professor Paul Zimmet of the WHO Collaborating Centre in Melbourne, Australia, and a world expert on IGT, noted, "although we have clear evidence that weight control and physical activity substantially reduce the risk of developing diabetes and CV disease, it's equally clear that many people do not respond to lifestyle advice" .
NAVIGATOR will be the largest diabetes prevention trial to date, involving 7500 subjects recruited from 600-800 centres in 40 countries. Participants will be aged at least 50 with at least one cardiovascular disease, or 55 years and older with at least one CV risk factor. In the four arm study, subjects will be randomised to receive Starlix (60mg before main meals), Diovan (160mg daily), both, or placebo. The effects of the two drugs will be assessed independantly. The NAVIGATOR protocol is under review with the U.S. Food and Drug Administration and European health authorities.
The study will be carried out in two phases. In the first phase, designed to run for three years after the last subject is enrolled, the effect of Starlix and Diovan on progression to diabetes will be evaluated. In the second, or 'extension' phase, the drugs' effects on CV disease will be evaluated. This phase will last until 1000 subjects have had a cardiovascular event. The total duration of NAVIGATOR follow-up is estimated at five years and nine months. It is expected that the first patient visit will take place in November 2001 and that recruitment will last 18 months.
Mealtime glucose spikes have been identified as an important risk factor for CV disease and mortality in people with type 2 diabetes. Starlix is an oral anti-diabetic drug which, when taken before main meals, rapidly stimulates a short-acting burst of insulin secretion, thereby reducing post-meal hyperglycaemia with minimal risk of subsequent hypoglycaemia. The pattern of insulin secretion produced by Starlix is similar to the physiological pattern of insulin secretion that is progressively lost in people with IGT and type 2 diabetes. Thus, in theory, Starlix is an ideal drug to use in the treatment of IGT.
Diovan is an angiotensin II receptor blocker (ARB) indicated for treatment of high blood pressure. Studies have shown that drugs that block the effects of angiotensin II reduce the incidence of cardiovascular disease in high-risk groups. Evidence is also emerging that these drugs may improve insulin sensitivity and reduce the risk of developing type 2 diabetes. Diovan is supported by the world's largest clinical trial program with an ARB, including several studies besides NAVIGATOR that are investigating its effects beyond blood pressure lowering. Diovan is also undergoing regulatory review worldwide for treatment of heart failure.
"The NAVIGATOR trial, which is nearly twice the size of any comparable trial, will show us whether restoration of early phase insulin secretion and improvements in insulin sensitivity can arrest decline to type 2 diabetes and prevent cardiovascular disease in this high-risk group" says Rury Holman, Professor of Diabetic Medicine, University of Oxford, UK, one of the trial's lead investigators. "Half of the people who develop type 2 diabetes already have complications by the time they are diagnosed. If we are to manage the growing tidal wave of type 2 diabetes, it is essential that we tackle the problem upstream".