Issue 104 Item 6 Starlix® (nateglinide) Enhances Early Insulin Secretion and Con

It is estimated that as many as 150 million people may have IGT. 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 an intermediate state between normal blood glucose control and type 2 diabetes and is characterized by an excessive rise in blood glucose following an oral glucose tolerance test. IGT is also a major risk factor for cardiovascular disease.

Dr Leif Groop of the University of Lund in Sweden, one of the study's lead investigators, commented, "Loss of early insulin secretion is one of the first pathophysiological signs of progression to type 2 diabetes. By restoring the normal, physiological pattern of insulin secretion, nateglinide essentially normalised glucose tolerance in these patients".

The study, which took place at centers in six European countries, involved 288 people with IGT (plasma glucose two hours after consuming 75 g glucose > or = 7.8mmol/l but <11.1 mmol/l and fasting plasma glucose < 7 mmol/l). Subjects were randomly allocated to take 30 mg, 60 mg, or 120 mg of Starlix® (nateglinide), or a placebo, before main meals for eight weeks. At the start and end of the study, blood glucose and insulin levels were measured at intervals for three hours after a standard meal.

The results showed that Starlix® (nateglinide) enhanced early insulin secretion and reduced both the size of the blood glucose peak and the total increase in blood glucose over the three hours following the meal. Fasting glucose levels were not affected.

Confirmed hypoglycemia (plasma glucose levels < or = 3.7 mmol/l or 67mg/Dl.) occurred in five (6.6%) subjects receiving 60 mg nateglinide and 23 (26.7%) of subjects taking the 120 mg dose. All symptoms were mild and quickly resolved.

"60 mg nateglinide was extremely well tolerated in these IGT patients," remarks Dr Groop. "The fast-on, fast-off, and glucose-dependent action of nateglinide means that the risk of hypoglycemia is minimal, even in these patients who do not yet have diabetes."

People with IGT are the ideal population to be involved in diabetes prevention trials. The mode of action of nateglinide and its excellent safety profile have led to its inclusion in the NAVIGATOR trial launched in November 2001. NAVIGATOR will be the largest diabetes prevention trial to date, involving 7,500 subjects in 40 countries, and will determine whether long-term administration of Starlix® (nateglinide) (60 mg before main meals) or the angiotensin II receptor blocker Diovan® (valsartan) (160 mg a day) prevents or delays type 2 diabetes and cardiovascular disease in people who have IGT and are at high cardiovascular risk.