|There has been considerable interest in the results from the ADOPT study (A Diabetes Outcome Progression Trial) which evaluated prospectively over 5 years the impact of rosiglitazone therapy, relative to metformin and glyburide, on the progression of type 2 diabetes.
In an interview, Lawrence Leiter, Professor of Medicine and Nutritional Sciences, University of Toronto, Canada, discusses the results and their clinical implications:
The UK Prospective Diabetes Study (UKPDS) showed that both metformin and sulphonylureas were associated with a progressive rise in fasting sugar and glycated haemoglobin in patients with type 2 diabetes over the duration of the study. The aim of the ADOPT study was to investigate whether rosiglitazone, relative to glyburide and metformin, was associated with more sustained reductions in blood sugar levels over a median treatment period of 4 years. Approximately 1,500 patients were randomized to each of the three treatment arms.
The study found that rosiglitazone achieved sustained glycaemic control and prolonged the time to treatment failure which was defined as the time to fasting plasma glucose levels greater than 180 mg/dL (10 mmol/L). Therapy with rosiglitazone was associated with a 32% risk reduction of treatment failure compared with metformin and a 63% risk reduction compared with glyburide (p < 0.001 for both comparisons). These benefits were confirmed by two further investigations of sustained glycaemic control namely - time to fasting plasma glucose levels above 140 mg/dL (among patients ≤ 140 mg/dL at baseline) and glycated haemoglobin levels.
In keeping with findings from previous studies, rosiglitazone was associated with a greater weight gain (approximately 5 kg) and oedema, while metformin was associated with a higher incidence of gastrointestinal events and glyburide with a higher incidence of hypoglycaemia relative to the other treatment groups. A surprise finding from ADOPT was that rosiglitazone was associated with a higher incidence of lower limb fractures (but not hip or vertebral fractures).
|The benefits observed with rosiglitazone were primarily the results of improved insulin sensitivity, but also a small improvement in beta-cell function. It is likely that as a consequence of the results from ADOPT, rosiglitazone may move up the treatment hierarchy, replacing sulphonylureas as second-line therapy. It is likely, however, that metformin will remain a first-line treatment.
Cape City - IDF December 2006