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* Key challenges of type 2 diabetes * * Over time, glycaemic control deteriorates UKPDS clearly showed the need for new diabetes treatments In UKPDS, the yearly median HbA1c in patients receiving conventional treatment increased steadily throughout the trial. In contrast, median HbA1c fell during the first year in patients receiving intensive treatment (glibenclamide, metformin or insulin) but gradually increased subsequently and only remained within the recommended treatment target for the first 3–6 years of treatment (depending on assigned treatment). During the remaining years of follow-up, median HbA1c continued to rise steadily above treatment targets. This failure of existing treatments, even when used intensively in highly motivated patients highlights the need for new treatments in the management of type 2 diabetes. UKPDS recruited 5102 patients with newly diagnosed type 2 diabetes; 4209 were randomised. The patients were treated for a median of 4.0 years. Conventional therapy aimed to maintain fasting plasma glucose (FPG) at < 15 mmol/l (270 mg/dl) using diet alone initially. However, sulphonylureas, insulin or metformin could be added if target FPG was not met. References UKPDS 34. Lancet 1998;352:854–865 UKPDS 33. Lancet 1998;352:837–853 ADOPT The more recent ADOPT study supports this. In the ADOPT study, rosiglitazone, metformin, and glibenclamide were evaluated as initial treatment for recently diagnosed type 2 diabetes in a double-blind, randomized, controlled clinical trial involving 4360 patients. The study showed that HbA1c increases with time, irrespective of OAD choice. Kahn et al (ADOPT). NEJM 2006;355(23):2427–43 * * Most therapies results in weight gain over time The influence of diabetes treatment on weight was evident in the UKPDS study (UKPDS 34): regardless of treatment, patients gained weight. Patients treated with insulin showed the largest weight increase, with an average gain of 4.0 kg more than conventional therapy at 10 years (
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