Public Release: 

New studies report AVANDIA may have the potential to reduce cardiovascular risk by targeting a fundamental cause of Type 2 diabetes

Shire Hall Communications

Data announced at the 61st Annual Meeting of the American Diabetes Association (ADA)

25th June 2001, Philadelphia, USA - New study results announced at the ADA demonstrate that AVANDIA® (rosiglitazone maleate) may have the potential to reduce cardiovascular risk in patients with Type 2 diabetes due to its beneficial effect on insulin resistance.1-3 AVANDIA®, a PPAR (Peroxisome Proliferator-Activated Receptor) gamma agonist (also known as a 'glitazone' or 'thiazolidinedione') directly targets insulin resistance. Insulin resistance is a fundamental defect of Type 2 diabetes and is associated with a number of cardiovascular risk factors.4 Cardiovascular disease and related events are key medical complications associated with Type 2 diabetes as well as primary cost drivers.5-7

Professor Enzo Bonora from the University of Verona, Italy, said today, "I am extremely encouraged by the results presented at ADA which clearly demonstrate Avandia's ability to significantly reduce insulin resistance, and I hope that these data could translate into better cardiovascular outcomes in patients. This is positive news as there are approximately 190 million people worldwide who suffer from Type 2 diabetes and most of them are at high risk of dying from cardiovascular disease."

Professor Bonora reported final results from three trials, involving over 1,000 patients with Type 2 diabetes, which evaluated the effects of AVANDIA® on insulin resistance in combination with traditional therapy (sulphonylurea [SU] or metformin [MET]) compared with traditional therapy alone, and as monotherapy compared to glyburide (glibenclamide). In the two 26 week combination trials, statistically significant reductions in insulin resistance were only achieved with AVANDIA® plus SU or MET. The results were consistent to the third study, a monotherapy trial which demonstrated a notably significant reduction in insulin resistance with AVANDIA® compared with glyburide.

"What is important here is that although insulin resistance is associated with cardiovascular risk factors, insulin resistance itself seems to be a major independent risk factor for cardiovascular disease" comments Dr Bonora. "Based on these data and previous studies, it is anticipated that a reduction in insulin resistance may have beneficial consequences for cardiovascular complications by reducing risk up to 25-30%."

A separate study which was intended to evaluate the effects of AVANDIA® on C-Reactive Protein, interleukin-6 and white blood cell count (non traditional factors associated with cardiovascular risk) in patients with Type 2 diabetes was also presented this week at ADA.2 The study results concluded the positive effects of AVANDIA® on these factors may be related to a change in insulin resistance and therefore could have a potentially positive impact on long-term cardiovascular risk.

"There is increasing evidence suggesting a relationship between amelioration of insulin resistance and reducing the cardiovascular risk. Trials assessing the direct relationship between the amelioration of insulin resistance and the decreased risk of cardiovascular events are now underway" concluded Professor Bonora.

Additional data presented today at ADA8,9 highlights that unlike traditional therapy, AVANDIA® targets both fundamental causes of Type 2 diabetes - insulin resistance and beta-cell function. The results of a study which evaluated the mechanisms by which AVANDIA® improves glycaemic control demonstrated that by reducing insulin resistance and preserving beta-cell function, AVANDIA® provides sustained improvements in glycaemic control; this normalised glycaemia in some of the pre-diabetic patients studied, whereas no patients normalised on glibenclamide. Although this was a small study this encouraging data supports previous evidence which shows AVANDIA® in combination with metformin or a sulphonlyurea sustains improvements in glycaemic control for up to two years.10,11

AVANDIA® is now approved for use in 66 countries worldwide. In the US alone, approximately ten million prescriptions have been written and the cumulative number of patients who have received AVANDIA® is approximately two million.

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GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

For further information please contact Laura Tipple or Siân Boisseau, Shire Hall Communications, 0207 313 6300. GSK press contact: Rebecca Fisher-Pollard, 0208 990 9000

References
1. Leonard TB et al. Rosiglitazone May Reduce Insulin Resistance Related Cardiovascular Disease Risk in Patients with Type 2 diabetes. 61st American Diabetes Association Annual Meeting, 22nd-26th June 2001, Philadelphia, USA. Abstract number 1838-PO.
2. Fuell D et al. The Effect of Treatment with Rosiglitazone on C-Reactive Protein and Interleukin-6 in Patients with Type 2 Diabetes. 61st American Diabetes Association Annual Meeting, 22nd-26th June 2001, Philadelphia, USA. Abstract number 1813-PO.
3. Weston W et al. Rosiglitazone-Mediated Reductions in Urinary Albumin Excretion are Associated with Changes in Ambulatory Blood Pressure in Type 2 Diabetes Patients. 61st American Diabetes Association Annual Meeting, 22nd-26th June 2001, Philadelphia, USA. Abstract number 541-P.
4. Groop LC. Insulin Resistance: The Fundamental Trigger of Type 2 diabetes. Diabetes, Obesity and Metabolism. May 1999:1(Supplement 1):S1-S7.
5. Brown JB, Pedula KL, Bakst AW. The Progressive Cost of Complications in Type 2 Diabetes Mellitus. Archives of Internal Medicine 1999;159:1873-1880.
6. Selby JV et al. Excess Costs of Medical Care for Patients with Diabetes in a Managed Care Population. Diabetes Care 1997;20:1396-1402.
7. Glauber H and Brown JB. Impact of Cardiovascular Disease on Health Care Utilization in a Defined Diabetic Population. J. Clin. Epidemiol 1994:47:1133-1142.
8. Dostou J et al. Mechanisms by which rosiglitazone improves glycaemic control in Type 2 diabetes mellitus. 61st American Diabetes Association Annual Meeting, 22nd-26th June 2001, Philadelphia, USA. Abstract number 2161-PO.
9. Deacon et al. Rosiglitazone is Effective in Obese and Non-Obese Patients with Type 2 Diabetes. 61st American Diabetes Association Annual Meeting, 22nd-26th June 2001, Philadelphia, USA. Abstract number 1804-PO.
10. Jones NP et al. Long term efficacy of rosiglitazone as monotherapy or in combination with metformin. Diabetologia 2000;43(Supplement 1): A192, Abs 736 and Poster.
11. GlaxoSmithKline Data on File. Long term efficacy of rosiglitazone added to sulphonylureas (AVDF0330A).

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