Antidiabetic agent - rivoglitazone
The growing global epidemic of Type II diabetes means that there remains a need for better, safer medicines to treat it. The glitazone drugs act as insulin sensitisers by agonising the peroxisome proliferator activated receptor, or PPARγ. The drugs decrease insulin resistance by enhancing the activity of insulin in the liver, adipose tissue and skeletal muscle. Two have been on the market for a decade - GSK's rosiglitazone (Avandia) and Lilly's pioglitazone (Actos) but in recent years the class has been dogged by concerns about potential cardiac side-effects. Several other glitazones are in development, including Daiichi Sankyo's rivoglitazone.
The growing global epidemic of Type II diabetes means that there remains a need for better, safer medicines to treat it. The glitazone drugs act as insulin sensitisers by agonising the peroxisome proliferator activated receptor, or PPARγ. The drugs decrease insulin resistance by enhancing the activity of insulin in the liver, adipose tissue and skeletal muscle. Two have been on the market for a decade - GSK's rosiglitazone (Avandia) and Lilly's pioglitazone (Actos) but in recent years the class has been dogged by concerns about potential cardiac side-effects. Several other glitazones are in development, including Daiichi Sankyo's rivoglitazone.
Trials include a double blind, randomised proof of concept study.1,2 A total of 426 patients with Type II diabetes were given 0.5, 2 or 5mg daily doses of rivoglitazone, or placebo or open label pioglitazone. The three doses gave respective reductions of fasting plasma glucose levels of 12, 39 and 51mg/dl, whereas the reduction with 30mg doses of pioglitazone was 19mg/dl. The new drug also gave better glycaemic control and lower lipid levels than pioglitazone.
A longer term trial has also been carried out. Again, this double blind, randomised trial, carried out over 26 weeks was a comparative trial against pioglitazone.3 The primary output was a reduction in glycosylated haemoglobin, or HbA1C, levels. This was significantly higher in subjects given placebo, and unchanged in the 1mg rivoglitazone and 45mg pioglitazone patients. It was significantly lower in those given 2 and 3mg rivoglitazone, with reductions of 0.4% and 0.5% respectively. The changes observed in fasting glucose were consistent with these reductions.
The new agent also gave a dose-dependent decrease in triglyceride levels, and increased high density lipoprotein cholesterol levels. No serious side-effects related to the treatment were observed, with the most frequent being weight gain and peripheral oedema. Further Phase II and Phase III trials are under way.