Issued 30 July 2007

A study analyzing data on more than 400,000 type 2 diabetes patients in a real-world setting provides strong evidence that Avandia is not associated with the increased risk of heart attack suggested as part of a previously published meta-analysis.

The study showed that there was no increased risk of heart attack or coronary revascularization among patients taking Avandia compared to Actos and/or the two most commonly prescribed oral diabetes treatments, metformin and sulfonylureas.

The GSK-commissioned observational study used health insurance claims data from a database that includes more than 80 US healthcare plans with more than 50 million unique patients from 2000 to 2007. The results have been submitted to the U.S. Food and Drug Administration and will be presented July 30 at an FDA advisory committee meeting. The study examines cardiovascular ischemic outcomes among many more patients than in previous studies of this nature, and GSK is not aware of any other study comparing the real-world use of Avandia and Actos.

These data support the results of a similar study published in June of more than 33,000 type 2 diabetes patients from a different data set, which also showed that the incidence of hospitalizations for heart attack, and/or for coronary revascularization for patients on Avandia is the same as for metformin and sulfonylureas. Those study results were released in a paper titled “Coronary Heart Disease Outcomes in Patients Receiving Antidiabetic Agents” in Pharmacoepidemiology and Drug Safety.

The study was designed to compare the risk of heart attack and coronary revascularization in type 2 diabetes patients taking specific therapeutic regimens including: monotherapy with thiazolidindiones (TZDs) (Avandia, Actos), metformin and sulfonylureas alone; dual therapy with any two of these agents; or any of these agents in conjunction with insulin. Cardiovascular death could not be assessed in this study as it is not captured in the claims databases.

Specifically, the findings show:

- In patients taking a single treatment, there was essentially no difference in the rate of heart attack or coronary revascularization between Avandia and Actos (hazard ratio 0.97, 95% confidence interval, 0.78 — 1.20). The TZDs had no statistically significant differences from metformin and sulfonylureas.

- In patients taking a combination of two treatments, rates of heart attack and/or coronary revascularization were essentially the same across all tested comparisons; combinations of Avandia with metformin or a sulfonylurea were not meaningfully different from the commonly used combination of metformin and a sulfonylurea. In addition, the rates were similar when either Avandia or Actos were combined with metformin (hazard ratio 0.97, 95% confidence interval 0.81 — 1.17) or sulfonylureas (hazard ratio 1.12, 95% confidence interval 0.89 — 1.41). (These are the rates for head to head comparisons of Avandia and Actos in combination with metformin and sulfonylureas, respectively.)

- When treatments were combined with insulin, the combined risk of heart attack and/or coronary revascularization was essentially the same in Avandia and Actos groups (hazard rate 1.07, 95% confidence level 0.89 — 1.29) and the combination of either of these with insulin had similar risks to combinations of either sulfonylureas or metformin with insulin.

- The statistical analyses do not support a 40 percent or greater risk of heart attack in patients taking Avandia as suggested in a meta-analysis published online May 21 in the New England Journal of Medicine.

Avandia is an effective medicine that is an important treatment for millions of patients who are using it to manage their diabetes, a disease with potentially devastating consequences if left unmanaged.

Important safety information for Avandia® (rosiglitazone maleate)

Avandia, along with diet and exercise, helps improve blood sugar control. It may be taken alone or with other diabetes medicines. For some people taking Avandia, possible side effects include heart failure or other heart problems. Further information regarding potential heart-related risks is currently under review by the FDA. Talk to your doctor as FDA has made information on potential heart-related risks available to physicians on its website at www.fda.gov. Tell your doctor if you have heart problems or heart failure. Avandia can cause your body to keep extra fluid, which leads to swelling and weight gain. Extra body fluid can make some heart problems worse or lead to heart failure. If you have swelling or fluid retention, shortness of breath or trouble breathing, an unusually rapid increase in weight, or unusual tiredness while taking Avandia, call your doctor right away. You should not take Avandia if you have liver problems. Blood tests should be used to check for liver problems before starting and while taking Avandia. Tell your doctor if you have liver disease, or if you experience unexplained tiredness, stomach problems, dark urine or yellowing of skin while taking Avandia. Tell your doctor about all of the medicines you are taking. If you are taking Avandia with another diabetes medicine that lowers blood sugar, you may be at increased risk for low blood sugar. Ask your doctor whether you need to lower the dose of your other diabetes medicine. Avandia may increase your risk of pregnancy. Talk to your doctor before taking Avandia if you could become pregnant or if you are pregnant. If you are nursing, you should not take Avandia. Talk to your doctor for advice on how to keep your bones healthy. More fractures, usually in the upper arm, hand, or foot, have been seen in women taking Avandia. Your doctor should check your eyes regularly. Very rarely, some people have experienced vision changes due to swelling in the back of the eye while taking Avandia.