Clinical trial results presented at the American Diabetes Association annual meeting show that overall rates of cardiovascular hospitalization and cardiovascular death are similar in patients taking Avandia (rosiglitazone) compared to those receiving metformin and sulfonylurea.

Results from the 4,447-patient Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study, which was sponsored by GlaxoSmithKline, Avandia's maker, were also published online in the medical journal The Lancet.

RECORD is a large, prospective, randomized, controlled study that was initiated in 2001, and designed to compare cardiovascular outcomes of patients on Avandia added to metformin or sulfonylurea to those on metformin and sulfonylurea. The study confirmed its primary hypothesis. It showed that cardiovascular hospitalization or cardiovascular death (which includes heart attack, congestive heart failure, and stroke) was not statistically different between the two groups after an average of 5.5 years of therapy. This translates into 321 events (14.5 per cent) among patients receiving Avandia compared to 323 events (also 14.5 per cent) for patients receiving control medications (hazard ratio=0.99, 95 per cent confidence interval=0.85 to 1.16) (Data on the individual components are provided below.)

"RECORD provides a robust assessment of rosiglitazone's cardiovascular safety and achieving the study's primary endpoint leads us to conclude that rosiglitazone carries no increased risk of overall cardiovascular death or hospitalization compared to the most commonly used diabetes medicines, metformin and sulfonylurea, which have been used for decades," said Dr Philip D Home, chairman of the RECORD Steering Committee and a professor at Newcastle University. "Millions of patients with diabetes do not achieve good blood sugar control, even with combination therapy, making a wide range of therapeutic options critical for the management of this growing and deadly disease."

Glycaemic control, as measured by mean haemoglobin A1c, was statistically significantly better in the patient group randomized to Avandiaafter the average of 5.5 years of treatment in the trial. RECORD's glycaemic result is consistent with the superior long term glycaemia control (for nearly five years) previously demonstrated by Avandia versus metformin and sulfonylurea in the ADOPT study.

Although RECORD was not designed to study microvascular endpoints, previous studies such as the United Kingdom Prospective Diabetes Study, which studied other medicines, have found that improved glycaemic control may reduce complications of diabetes that can lead to amputations, kidney failure and eye damage.

Congestive heart failure is a known effect of Avandia and other drugs in the thiazolidinedione (TZD) class and is prominently described in a boxed warning in current labels of both TZDs. As anticipated, rates of CHF in RECORD were higher in the group randomized to Avandia (61 events or 2.7 per cent versus 29 events or 1.3 per cent) (hazard ratio=2.10, 95 per cent confidence interval=1.35 to 3.27). The difference was statistically significant.

Other adverse events in patients randomized to Avandia were consistent with those reported in the US. Prescribing Information for Avandia, including bone fractures, which were higher in the group randomized to Avandia and were seen mostly in the bones of the arm, hands, lower leg and feet, and predominantly in women.

Among patients randomized to Avandia, the results for the following prespecified secondary endpoints also showed:

RECORD showed no evidence of an increase in malignancies. There were fewer events of pancreatic cancer in patients taking Avandia although the numbers were small.

"RECORD provides important and reassuring information about Avandia for physicians fighting diabetes," said Dr Ellen Strahlman, GSK's chief medical officer. "Clinical outcomes trials like this offer the highest standard of evidence when considering the benefits and risks of medicines. RECORD clearly demonstrates that overall rates of cardiovascular hospitalization and death are similar in patients taking Avandia compared to those receiving metformin and sulfonylurea. We believe that Avandia remains an important diabetes medicine for the appropriate patients."

Avandia, introduced on the market in 1999, is a member of the TZD class of oral anti-diabetic medications which improve blood sugar control by directly targeting insulin resistance, an underlying cause of type-2 diabetes. This helps the body respond better to its own natural insulin. Avandia is indicated as an adjunct to diet and exercise to improve glycaemia control in patients with type-2 diabetes mellitus.

More than 18 million Americans have type-2 diabetes, making it the most common form of diabetes, which accounts for about 90 to 95 per cent of diagnosed diabetes cases. Type-2 diabetes has been associated with a variety of serious health problems including heart disease, stroke, eye damage, kidney failure and foot problems that lead to amputations.