Jerusalem, Israel, 18 September 2000: Addressing insulin resistance and declining beta-cell function may be the key to delaying the progression of type 2 diabetes, according to experts at the annual conference of the European Association for the Study of Diabetes (EASD).

A new treatment, Avandia^TM (rosiglitazone), is now available in Europe that may address this dual therapeutic need. Unlike conventional oral anti-diabetic therapies, Avandia^TM targets both fundamental causes of type 2 diabetes; reducing insulin resistance and potentially improving beta-cell function.^1,2 By doing this, Avandia^TM provides enhanced and sustained glycaemic control^3,4,5,6 and may have the potential to alter disease outcomes and delay disease progression.

Data show a 23% improvement in beta-cell function when Avandia^TM (8 mg/day) is added to metformin therapy in a Homeostasis Model Assessment (HOMA) study*.⁷ This may reflect Avandia^TM’s ability to reduce elevated blood glucose and free fatty acid levels,7 factors characteristic of type 2 diabetes that appear to be toxic to the pancreatic beta-cells.^8,9

Significantly, a preclinical study showed that Avandia^TM may have a protective effect on the beta-cells.¹⁰ "In animal studies, we found that Avandia^TM prevented the loss of â-cell mass in rats treated before the development of diabetes," reported Dr Diane Finegood, lead investigator of the study. "Maintenance of â-cell mass was associated with less â-cell death as compared to untreated animals. This suggests that, in this model, the progression to type 2 diabetes can be delayed."

As type 2 diabetes progresses insulin resistance increases and the beta-cells can no longer compensate, so it becomes harder to maintain good glycaemic control -- even with combination therapy. This may be due, in part, to the fact that conventional oral anti-diabetics do not directly treat the underlying causes of the disease, particularly insulin resistance.¹

Avandia^TM (8 mg/day) in combination with metformin therapy was also shown to reduce insulin resistance by 20% compared to baseline.² Furthermore, adding Avandia^TM (4 mg/day) to sulphonylurea treatment decreased insulin resistance by 17% compared to baseline.²

Importantly, the effects of Avandia^TM, in combination with metformin, on insulin resistance and beta-cell function are maintained for at least 2 years.^7,11 This may account for the sustained improvements in glycaemic control seen with Avandia^TM treatment and suggests that it may delay disease progression.

At present, the ability of treatments to maintain effective glycaemic control declines markedly with time; approximately half of patients on monotherapy must progress to combination therapy within 3 years.¹²Through its novel mode of action, Avandia^TM has the potential to substantially improve the management of type 2 diabetes in patients with unmet medical needs.

* Homeostasis Model Assessment (HOMA) is a method for estimating insulin resistance and beta-cell function in patients with type 2 diabetes.

SmithKline Beecham -- one of the world’s leading healthcare companies -- discovers, develops, manufactures, and markets pharmaceuticals and vaccines, over the counter medicines, health-related consumer products. For company information, visit SmithKline Beecham on the World Wide Web at http://www.sb.com .

Note to Editors:

Avandia^TM (rosiglitazone) is the first PPAR (peroxisome proliferator-activated receptor) gamma agonist (thiazolidinedione; glitazone) to receive a product licence in the EU via the centralised procedure. Avandia^TM is now available in more than 50 countries worldwide. SmithKline Beecham has committed to a programme of clinical investigations worth more than £100 million in Europe alone -- one of the biggest diabetes programmes recorded.

Avandia^TMTM is a trademark of SmithKline Beecham plc.

References

1. Kobayashi M. Effects of current therapeutic interventions on insulin resistance. Diabetes, Obesity and Metabolism 1999; 1 (Supplement 1):S32--S40.

2. Matthews DR, Bakst AW, Weston WM, et al. Rosiglitazone decreases insulin resistance and improves beta-cell function in patients with type 2 diabetes. Diabetologia 1999; 42 (Supplement 1) :A228.

3. Fonseca V, Rosenstock J, Patwardhan R, et al. Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA 2000; 283:1695--1702.

4. SmithKline Beecham. Data on file to support long-term safety and efficacy of rosiglitazone in combination with metformin in obese patients. 2000.

5. SmithKline Beecham. Data on file to support long-term safety and efficacy of rosiglitazone in combination with sulphonylureas in patients with renal insufficiency. 2000.

6. Wolffenbuttel BH, Gomis R, Squatrito S, et al. Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in Type 2 diabetic patients. Diabetic Medicine 2000; 17:40--47.

7. Jones NP, Mather R, Owen S, et al. Long-term efficacy of rosiglitazone as monotherapy or in combination with metformin. Submitted to EASD 2000.

8. Paolisso G & Howard BV. Role of non-esterified fatty acids in the pathogenesis of type 2 diabetes mellitus. Diabetic Medicine 1998; 15:360--366.

9. Rossetti L, Giaccari A & DeFronzo RA. Glucose toxicity. Diabetes Care 1990; 13:610--630.

10. Finegood DT, McArthur MD, Buckingham RE, et al. Rosiglitazone reduces net loss of pancreatic beta-cell mass in Zucker diabetic fatty rats. Submitted to EASD 2000.

11. SmithKline Beecham. Data on file (CMAT presentations). 2000.

12. Turner RC, Cull CA, Frighi V, et al. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999; 281:2005--2012.

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