Type II diabetes - exenatide
Type II diabetes is a growing problem in the developed world, with the WHO predicting that the number of sufferers will double from around 150m in 2000 to 300m in 2005.
Type II diabetes is a growing problem in the developed world, with the WHO predicting that the number of sufferers will double from around 150m in 2000 to 300m in 2005.
There are two main forms of the condition: Types I and II. People with Type I, also known as insulin-dependent diabetes or juvenile-onset diabetes, are unable to produce their own insulin in the pancreas.
Those with Type II - adult-onset or non-insulin dependent diabetes - are more likely to produce enough insulin, but their bodies are incapable of using it effectively. A variety of different forms of drug therapy are used to treat Type II diabetes, including sulfonyl-ureas, biguanides, and a range of insulin sensitisers like the glitazone drugs.
Now, a new class is being investigated by Amylin Pharmaceuticals: incretin mimetics. The first of these drugs, exenatide, is now being developed in conjunction with Eli Lilly and Alkermes.1
Glucagon like peptide 1 (GLP-1) is a naturally occurring incretin hormone that stimulates the body to produce insulin in response to rising blood sugar levels. It also inhibits the release of glucagon after eating, and reduces the rate at which nutrients are absorbed into the bloodstream. But the peptide itself is not therapeutically useful, as its half life is too short. Exenatide is a synthetic version of a peptide isolated from Gila monster venom; it has a similar effect to GLP-1 but is both more stable and longer acting.
Three pivotal randomised Phase III trials have been carried out.2 Patients were given exenatide or placebo, with those given the active first dosed subcutaneously twice a day for a month with 5µg of the peptide, then either 5 or 10µg twice a day for six months. A trial involving 336 patients who had had unsatisfactory results with metformin alone showed statistically significant dose dependent reductions in the primary glucose control endpoint.2 In the second trial, 377 patients for whom sulfonylurea drugs had been ineffective were randomised to receive exenatide or placebo. Those given exenatide saw similar improvements to those in the metformin patient trial, with the best improvement seen in those given the highest dose.
In the third study, 734 patients who had been unsuccessful with a combination of metformin and sulfonylureas were treated. Again, good results were seen with those given the peptide.