Treatment of insulin resistance may have the potential to reduce long-term complications of type 2 diabetes

September 28, 1999

Brussels, Belgium, 28 September 1999: New data presented at this week's European Association for the Study of Diabetes (EASD) meeting in Brussels show that the new oral treatment for type 2 diabetes, rosiglitazone, reduces insulin resistance, offering glycaemic control and additional beneficial effects on other important risk factors of the disease. Results suggest that rosiglitazone may have the potential to reduce late-stage complications.

"The new studies show that by directly targeting insulin resistance, one of the fundamental defects in type 2 diabetes, rosiglitazone treatment may improve a whole range of metabolic abnormalities," said Dr George Bakris of the Rush University Hypertension Center, Chicago, USA.

Insulin resistance is a fundamental defect in type 2 diabetes, and the risk of coronary heart disease is approximately doubled in individuals with insulin resistance, regardless of whether the person also has type 2 diabetes. (1) Other associated metabolic changes, such as high blood concentrations of insulin and excretion of a protein known as albumin in the urine, are also 'markers' for the risk of coronary heart disease. (2,3)

A series of new studies being presented at EASD show that rosiglitazone, by directly reducing insulin resistance, gives long-term control of blood glucose (4,5) as well as offering other benefits.

Reduced insulin resistance . Using an indirect method of analysis, without invasive tests, investigators report that rosiglitazone monotherapy (8 mg/day) reduced insulin resistance by 33% compared with placebo in just 26 weeks of treatment. Rosiglitazone was also added to existing treatment with another oral anti-diabetes drug (a sulphonylurea). When compared with sulphonylurea plus placebo, the addition of rosiglitazone (4 mg/day) reduced insulin resistance by 32% over 26 weeks. Over 1400 individuals with type 2 diabetes were included in these studies. Some were new to drug therapy and others had received previous treatment with oral anti-diabetes drugs. (6)

Reduced insulin levels in the blood . Investigators report significant reductions in insulin concentrations in the blood of up to 18% with rosiglitazone. These reductions are consistent with a reduction in insulin resistance. In contrast, sulphonylurea therapy in a comparable group of individuals increased insulin concentrations by 23%. 587 individuals with type 2 diabetes were involved in the 12-month study. (7)

Reduced protein excretion . Investigators also report that treatment with rosiglitazone (8 mg/day) reduced albumin excretion measured in the urine by 26% after 52 weeks of treatment. Sulphonylurea therapy reduced urinary albumin excretion by just 9% in the same period. In this 12-month study, 203 patients were randomly assigned to receive either sulphonylurea or rosiglitazone treatment. (3)

In addition, individuals with poorly controlled type 2 diabetes often also suffer from a dyslipidaemia. This is characterized by abnormalities in the way they metabolise fats, which may lead to high levels of both triglycerides and free fatty acids in the blood, and a high total cholesterol:HDL cholesterol (the 'good' cholesterol) ratio. Dyslipidaemia is strongly linked with insulin resistance and increased cardiovascular risk. (8,9) The new studies also show the following effects of rosiglitazone treatment on these cardiovascular factors:

Reduced triglycerides . Investigators report that, overall, the changes in triglycerides after 26 weeks of treatment with rosiglitazone were not different from placebo. In patients with elevated triglyceride levels at baseline (400 mg/dl), triglycerides decreased during the course of treatment with rosiglitazone. (10)

Reduced free fatty acids . Investigators report significant reductions in free fatty acids compared with treatment with a sulphonylurea. According to the investigators, "the reductions with rosiglitazone were greater than could be explained by the concomitant improvements in glycaemia" (blood glucose control). This study treated 587 patients with either a sulphonylurea or rosiglitazone." (5)

Long-term improvements in the total cholesterol:HDL cholesterol ratio . Investigators looked at pooled data from 534 patients who have received rosiglitazone monotherapy (8 mg/day) for more than 18 months. Although short term increases in LDL have been reported with rosiglitazone (plateauing at 12 months), increases in HDL have been shown to continue over the course of 18 months, with a subsequent improvement in the total cholesterol:HDL cholesterol ratio. (5,10)

Dr Bakris concludes: "The fact that recognised risk factors are reduced by rosiglitazone raises the hope that treatment of insulin resistance may, in the long term, reduce the heavy burden of disease complications in people with type 2 diabetes."
-end-
Note to Editors

SmithKline Beecham's Avandia® (rosiglitazone maleate) received approval on 25 May 1999 from the US Food and Drug Administration (FDA) for the treatment of type 2 diabetes, both as 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 Agency for the Evaluation of Medicinal Products (EMEA) and in over 40 other markets worldwide.

References

  1. Strutton D, Stang P, Erbey JR, et al . Increased coronary heart disease associated with insulin resistance in populations with and without type 2 diabetes. Poster 1053 presented at EASD 1999.
  2. DeFronzo RA & Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991; 14:173­194.
  3. Bakris G, Weston WM, Rappaport EB, et al . Rosiglitazone produces long-term reductions in urinary albumin excretion in type 2 diabetes. Poster 865 presented at EASD 1999.
  4. 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.
  5. Lönnqvist F, Charbonnel B, Jones NP, et al . Rosiglitazone is superior to glibenclamide in reducing fasting plasma glucose in type 2 diabetic patients. Poster 869 presented at EASD 1999.
  6. 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.
  7. 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.
  8. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37:1595­1607.
  9. Haffner SM, D'Agostino RJ, Mykkanen L, et al. Insulin Sensitivity in Subjects with Type 2 Diabetes. Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study. Diabetes Care 1999; 22:562­568.
  10. Tabona MV, Weill S & Patwardhan R. Rosiglitazone given once or twice daily is effective first-line treatment for type 2 diabetes mellitus. Poster 867 presented at EASD 1999.

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