Antidiabetic —farglitazar
Diabetes mellitus is an increasing problem, with the World Health Organisation anticipating that around 300 million people worldwide will be suffering from the condition by 2005. It is a chronic condition, where insulin is either not produced or used correctly, and is characterised by a high blood glucose level as a result of the body not using the carbohydrates ingested from food properly.
Type I, the insulin-dependent form, is more common in young diabetics and is generally treated by insulin injections, while Type II, often called mature-onset diabetes, is normally controlled by the use of oral antidiabetic agents. A novel class of these drugs currently being investigated is the peroxisome proliferator-activated receptor (PPAR) agonists. The PPARs are transcription factors involved in the storage and use of dietary facts, and three subtypes have been identified, of which the PPAR-g receptor is the target for antidiabetic research.
A number of thiazolidinone compounds, such as pioglitazone and rosiglitazone, have been developed as PPAR-γ agonists over the past few years, and they act as insulin sensitisers, but several have shown significant side-effects post-marketing, and non-thiazolidinone compounds may prove to be better.
GSK has been developing the tyrosine-based compound farglitazar as a potential treatment for Type II diabetes.1 It has a high affinity for the PPAR-γ recept0r. In a randomised double-blind placebo-controlled trial in 35 patients, significant reductions in blood glucose were seen, and continued for 24hr after the dose.2 A further study in 376 patients proved its efficacy as monotherapy in the control of Type II diabetes. It was found to be well tolerated, and have a similar safety profile to other PPAR-γ agonists.3
The compound is now undergoing Phase III trials to further evaluate its potential as an oral therapy for Type II diabetes.