ADOPT has (A Diabetes Outcome Progression Trial) demonstrated that initial treatment with Avandia (rosiglitazone maleate) reduced the risk of monotherapy failure in people with type 2 diabetes by 32 per cent compared to metformin and 63 per cent compared to glyburide at five years.

The results of this international study involving 4,360 people recently diagnosed with type 2 diabetes were published in the New England Journal of Medicine and presented at the 19th World Diabetes Congress of the International Diabetes Federation (IDF). 1

Rosiglitazone was more effective than metformin or glyburide in delaying the progressive loss of blood sugar control, as measured in the study by fasting plasma glucose (FPG) and glycosylated (or glycated) haemoglobin levels (HbA1c).1 The primary reasons for loss of blood sugar control are increasing insulin resistance and declining ß-cell function.2 ADOPT demonstrated that rosiglitazone significantly improved insulin sensitivity and reduced the rate of loss of ß-cell function 1

"ADOPT provides evidence supporting earlier treatment with rosiglitazone in the management of type 2 diabetes. This is the first long-term study to demonstrate that the progressive loss of blood sugar control can be delayed and target blood sugar levels can be maintained for a longer period with rosiglitazone than with metformin and glyburide - the two most frequently prescribed oral antidiabetic agents," said Dr Steven Kahn, professor of medicine, VA Puget Sound Health Care System and University of Washington School of Medicine, Seattle, Washington, US and Dr Giancarlo Viberti, professor of diabetes and metabolic medicine, King's College London School of Medicine, UK. "The more durable effect on blood sugar with rosiglitazone was also consistent with greater improvements in core defects of the disease, including significant effects on insulin resistance and ß-cell function."

ADOPT provides an important update to findings from the United Kingdom Prospective Diabetes Study (UKPDS) released in 1998, which preceded availability of thiazolidinediones (TZDs) and included only two of the three oral agents evaluated in ADOPT - metformin and sulphonylurea.3-5

Initial therapy with rosiglitazone delayed progressive loss of blood sugar control more effectively than metformin or glyburide using different blood sugar thresholds - from FPG >180 mg/dl to a lower blood sugar level more consistent with current therapeutic approaches, FPG >140 mg/dl 1,6,7 Long-term blood glucose control as measured by a mean HbA1c <7.0 per cent was maintained for longer with rosiglitazone - 60 months versus 45 months with metformin and 33 months with glyburide.1

"With ADOPT, we now have clear evidence from a large international study that the initial use of rosiglitazone is more effective than standard therapies for type 2 diabetes in maintaining blood sugar control," said Dr Lawson Macartney, senior vice president, cardiovascular and metabolic Medicine Development Centre, GSK. "ADOPT adds to the growing body of evidence released this year supporting the rationale for incorporating rosiglitazone as a cornerstone of treatment of type 2 diabetes by demonstrating patient benefits in terms of long-term glucose control."

In ADOPT, rosiglitazone was reported to be generally well tolerated among the large cohort of people with type 2 diabetes who were followed for up to six years. There was no significant difference between the rosiglitazone and metformin groups in treatment discontinuation, but the rate was higher for the glyburide group (44 per cent in the glyburide group; 38 per cent in the metformin group; 37 per cent in the rosiglitazone group). Largely a higher level of withdrawals due to hypoglycaemia drove this difference for people in the glyburide group.1

After the five-year period of study, commonly reported adverse events across the treatment groups were oedema (rosiglitazone 14.1 per cent; glyburide 8.5 per cent; metformin 7.2 per cent); weight gain (rosiglitazone 6.9 per cent; glyburide 3.3 per cent; metformin 1.2 per cent); gastrointestinal side effects (metformin 38.3 per cent; rosiglitazone 23.0 per cent; glyburide 21.9 per cent); and hypoglycaemia (glyburide 38.7 per cent; metformin 11.6 per cent; rosiglitazone 9.8 per cent).1