New treatment for type 2 diabetes puts insulin back to work

Brussels, Belgium, 28 September 1999: New data presented at the European Association for the Study of Diabetes (EASD) annual conference show that rosiglitazone ­ the new treatment for type 2 diabetes ­ gives individuals with this disease long-term control of their blood glucose levels by reducing one of the fundamental defects of this devastating condition.

Rosiglitazone is a novel oral anti-diabetic treatment that works by reducing insulin resistance ­ a defect where cells respond poorly to insulin, causing blood glucose levels to rise. Insulin resistance is not only a fundamental defect in type 2 diabetes ­ it is also commonly associated with a cluster of other conditions, including coronary heart disease and high blood pressure.(1)

"Unlike most traditional drugs for type 2 diabetes, rosiglitazone works in a novel way to reduce insulin resistance, helping the body¹s own insulin work more effectively and offering patients improved glycaemic control, as measured by fasting plasma glucose. The hope is that this will slow long-term deterioration," said Dr David Matthews of the Oxford Diabetes and Endocrinology Centre, Oxford, UK.

The new studies highlight the following important effects of rosiglitazone on insulin action:

Rosiglitazone reduces insulin resistance . Using an indirect method of analysis, which calculates insulin resistance without invasive tests, investigators reported that rosiglitazone (8 mg/day) alone reduced insulin resistance in individuals with type 2 diabetes by 33%, compared with placebo, in just 26 weeks. Rosiglitazone was also added to existing treatment with an oral anti-diabetes drug (a sulphonylurea). In this study, 493 type 2 diabetes patients, including those who were new to drug therapy and others who had been previously treated with diabetes drugs, were given either placebo or rosiglitazone monotherapy. Rosiglitazone was also compared to placebo in combination with sulphonylurea. Continued sulphonylurea treatment plus placebo led to an increase in insulin resistance of 15% compared to baseline, whereas a reduction in insulin resistance of 17% compared to baseline was noted with the addition of rosiglitazone (4 mg/day). (2)

Rosiglitazone improves pancreatic function . In the same study, investigators reported that, in six months, treatment with rosiglitazone (8 mg/day) increased the function of the insulin-producing cells of the pancreas (beta cells) by 60%. The function of the beta cells was also measured for the addition of rosiglitazone (4 mg/day) to existing treatment with a sulphonylurea. After 26 weeks, the combination of sulphonylurea and rosiglitazone led to an increase in function of 63%, compared with sulphonylurea therapy and placebo. (2)

Rosiglitazone reduces insulin levels in the blood . Investigators reported significant reductions in measured insulin concentrations in the blood of up to 18% with rosiglitazone treatment (8 mg/day). In contrast, sulphonylurea treatment in a comparable group of individuals led to an increase in insulin concentrations of 23%. 587 individuals with type 2 diabetes were involved in this 12-month study. (3)

In type 2 diabetes, the pancreas attempts to compensate for insulin resistance by producing extra insulin. Years of maintaining high levels of insulin resulting from insulin resistance may leave the beta cells exhausted. This exhaustion ultimately leaves many people with type 2 diabetes needing regular insulin injections.

Pre-clinical studies also being presented at EASD, comparing obese diabetic mice with lean littermates, suggest that rosiglitazone therapy may have the potential to exert a durable beta cell protective action in type 2 diabetes.4

By putting insulin back to work within the body, treatment with rosiglitazone means that a range of patients can achieve long-term control of blood glucose levels:

Investigators compared rosiglitazone with a sulphonylurea (a traditional oral anti-diabetes medicine) in 231 patients previously treated with diet and exercise alone. This study found that, after 12 months of treatment, rosiglitazone produced better glycaemic control as measured by fasting plasma glucose. Only 49% of individuals taking the sulphonylurea achieved the target fasting plasma glucose level compared with 74% of individuals taking rosiglitazone (8 mg/day). (5)

Other investigators studied the effects of rosiglitazone in individuals with poorly controlled type 2 diabetes (HbA1c > 9%)*, where previous treatments had failed to achieve adequate blood glucose control. Data was pooled from three multicentre, double-blind studies of rosiglitazone as monotherapy in 2,090 patients. According to these studies, rosiglitazone demonstrated clinically significant effects on both fasting plasma glucose and HbA1c at all doses and regimens, regardless of whether the drug was administered to patients previously treated with an anti-diabetic agent or with diet alone. These studies indicate that rosiglitazone is effective regardless of the starting level of glucose control.

*HbA1c is haemoglobin A1c ­ haemoglobin that has reacted with glucose in the blood. This is a useful indicator of the average level of a patient¹s blood glucose control in the previous 2­3 months. In the landmark United Kingdom Prospective Diabetes Study (UKPDS), HbA1c reductions of 1% were shown to significantly reduce the risk of the complications that place such a heavy burden on the health of people with type 2 diabetes. (7)

Dr Matthews concludes: "These findings suggest that rosiglitazone may have a role as an effective alternative to current first-line therapies for type 2 diabetes."

Note to Editors

SmithKline Beecham¹s Avandia® (rosiglitazone maleate) received approval on 25 May 1999 from the U.S. Food and Drug Administration (FDA) for the treatment of type 2 diabetes as both monotherapy and in combination with metformin. Rosiglitazone has received marketing approval in 15 countries, including the US, Mexico, Venezuela and Argentina. In addition, the product has been filed for regulatory approval with the European Medicines Evaluation Agency and in over 40 other markets worldwide.

References

1. Conn J & Betteridge DJ. Insulin resistance in cardiovascular disease. Aspects of Cardiovascular Medicine 1998; 5:329­336.
2. Matthews DR, Bakst AW, Weston WM, et al . Rosiglitazone decreases insulin resistance and improves beta-cell function in patients with type 2 diabetes. Poster 858 presented at EASD 1999.
3. Jones NP, Charbonnel B, Lönnqvist F, et al . Rosiglitazone reduces plasma insulin and its precursors while decreasing glycaemia in type 2 diabetics. Poster 859 presented at EASD 1999.
4. Lister C, Moore GBT, Piercy V, et al . Rosiglitazone, but not metformin or glibenclamide, improves glycaemic control and increases islet insulin content. Poster presented at EASD 1999.
5. Owen S, Charbonnel B, Lönnqvist F, et al . Rosiglitazone is an effective alternative to glibenclamide as first-line therapy in type 2 diabetic patients. Poster 868 presented at EASD 1999.
6. Goldstein B, Salzman A. Rosiglitazone is effective in poorly controlled type 2 diabetes patients. Poster 861 presented at EASD 1999.
7. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837­853.