Antidiabetic agent - taspoglutide
According to the WHO, Type 2 diabetes is reaching epidemic levels. In this form of the disease, patients become sensitised to insulin and therefore do not use the insulin their pancreas makes efficiently. While this can often be managed effectively by diet and exercise, particularly in the early stages, drug treatment usually becomes necessary. Numerous different therapeutic approaches are under investigation, including treatment with glucagon-like peptide 1 (GLP-1) analogues.
According to the WHO, Type 2 diabetes is reaching epidemic levels. In this form of the disease, patients become sensitised to insulin and therefore do not use the insulin their pancreas makes efficiently. While this can often be managed effectively by diet and exercise, particularly in the early stages, drug treatment usually becomes necessary. Numerous different therapeutic approaches are under investigation, including treatment with glucagon-like peptide 1 (GLP-1) analogues.
It is now known that metabolic mediators other than insulin are also involved in the pathogenesis of Type 2 diabetes. One of these is the incretin GLP-1; this is secreted by L cells in the ileum and is released into the bloodstream after food is consumed. It activates incretin receptors on the b-cells, which enhances the glucose dependent exocytosis of insulin, and also lowers glycaemia by decelerating gastric emptying, inhibiting glucagon secretion, and enhancing the disposal of glucose disposal in the peripheral tissues, as well as inhibiting food intake.
It also has longer term effects, such as enhancing the secretion of insulin - it has been shown to be responsible for about two-thirds of the insulin secretion response in normal subjects, but less than a fifth in those with Type 2 diabetes.
Studies have also shown that GLP-1 infusions can normalise insulin control in patients with Type 2 diabetes; however, as it is rapidly inactivated in the body by the enzyme dipeptidyl peptidase 4 (DPP4), a longer acting analogue would make a more effective therapeutic agent. Several of these are being investigated, including taspoglutide, initially developed by Ipsen and licensed to Roche, plus Teijin and Chugai in Japan, which has greater resistance to the DPP4 enzyme.
In a randomised, double blind, parallel group study, 51 patients with Type 2 diabetes who were being treated with metformin were given a continuous subcutaneous infusion of 100, 200, 400 or 800µg/day of taspoglutide or placebo over seven days. Those given the drug experienced a significantly reduced mean 24 hour glucose AUC, with the highest dose having the greatest effect; in addition, 24 hour insulin AUC increased and glucagon levels fell.1
Its effect over a longer period of time - 28 days - has also been investigated. Eighteen metformin-treated patients were given 400µg/day by continuous subcutaneous infusion or placebo. The treated group had improved glucose levels from the first day and throughout the treatment period.2
Another trial looked at the effect of single doses; 48 patients whose glucose levels were not well controlled with metformin were given a single subcutaneous injection of 1, 8 or 30mg or placebo; the highest dose significantly reduced blood glucose levels for up to two weeks, both fasting and after eating.3 They also lost weight. Another trial showed that weekly subcutaneous injections were similarly effective.4
A slow release formulation is also being looked at. This was given to 306 patients whose symptoms were inadequately controlled with metformin; they were given 5, 10 or 20mg of the drug once a week, 10 or 20mg every two weeks or placebo over eight weeks, and then followed for a further four weeks. The weekly version was more effective in controlling glucose levels, and looks promising as a potential therapy for Type 2 diabetes.5