Type II diabetes - vildagliptin

The number of people who suffer from Type II diabetes is escalating, and it now accounts for as many as 90% of those with diabetes in the developed world.

Often a result of poor diet and lack of exercise, the condition leaves patients increasingly unable to use the insulin they produce. To start with, it can often be controlled by exercise and diet, but most sufferers eventually need drug treatment.

A variety of different forms of drug therapy are used to treat Type II diabetes, including sulfonylureas, biguanides, and insulin sensitisers like the glitazone drugs. Another strategy is to intervene in the hormonal regulation process of insulin secretion. To this end, Novartis is developing vildagliptin,¹ a dipeptidyl-peptidase (DPP) IV inhibitor. DPP IV degrades the incretin hormone glucagon-like peptide-1 (GLP-1), which is involved in the control of glucose homeostasis in the body.

Numerous clinical trials have been carried out. A randomised, double blind crossover study was carried out in 16 healthy male subjects to establish the risk of reactive hypoglycaemia when vildagliptin was given alongside glibenclamide.² The minimal glucose concentration in an oral glucose tolerance test was much lower when glibenclamide was also taken, but the combination did not give a significant increase in the risk of developing hypoglycaemia.

A trial was also run to establish the mechanism by which it suppresses post-prandial glucagon secretion.³ A group of 12 patients were given 100mg of the drug or placebo twice a day for 28 days, and the active was found to reduce post-prandial glucose exposure by 12% and overall glucose exposure by 10% in the first two hours. This showed that its glucagonostatic effect was mediated by an endocrine effect, and is not dependent on endogenous insulin secretion.

Its effects were investigated in a multicentre double blind placebo-controlled trial in patients whose Type II diabetes was controlled by diet.⁴ Over a period of four weeks, they were given 100mg vildagliptin a day or placebo. After the four weeks, those given the active had significantly higher post-prandial active GLP-1, and both post-prandial and fasting glucose levels were lower, with insulin secretion being maintained.

Another trial looked at its efficacy in patients whose diabetes was not properly controlled by metformin.⁵ Over a 52-week period, subjects were given either 50mg of vildagliptin four times a day or placebo alongside metformin. Glucose levels were significantly lower, both during fasting and after eating, in those given the active. It was generally well tolerated, and Phase III trials are now under way.