Bristol-Myers Squibb decided to admit defeat and drop its diabetes drug Pargluva from development yesterday, just days after AstraZeneca discontinued work on a similar compound.

B-MS’ decision was almost inevitable, considering that the Food and Drug Administration told the company last year that it would have to conduct an additional Phase III study of Pargluva (muraglitazar), expected to take at least five years to complete. This prompted development partner Merck & Co to hand back sole rights to the compound to B-MS in December 2005.

The FDA wanted to know more about the drug's affect, if any, on cardiovascular health, after clinical data published in the Journal of the American Medical Association (November 23, 2005) showed there could be a higher-than-acceptable occurrence of heart attacks and other adverse events.

The company’s share price barely shifted in the wake of the announcement, indicating that investors had already discounted any contribution from muraglitazar to B-MS’ coffers in the coming years.

Muraglitazar is a dual alpha/gamma PPAR agonist, in the same class as AstraZeneca’s tesaglitazar, which was dropped from development last week.

In a statement, the company said it took the decision on the back of “analyses of existing studies with muraglitazar, results of outcomes studies with other PPAR alpha and gamma agonists, and the evaluation of the cardiovascular safety results from a recently-completed muraglitazar study.”

Several other compounds in this class, which were of particular interest as clinical candidates because they promised to tackle both insulin resistance and high blood lipids in type 2 diabetes, have already fallen by the wayside because of toxicity. Side effects have been varied, including oedema, raised levels of hepatic enzymes and tumours in rodents.

Casualties include Takeda's TAK-559, Novo Nordisk/Dr Reddy's Laboratories' ragaglitazar, Japan Tobacco's reglitazar and Merck & Co's MK-767.

B-MS has two other diabetes drugs in its pipeline, including the long-acting dipeptidyl peptidase IV inhibitor saxagliptin (BMS-477118), which is in Phase III testing, and an SGLT2 inhibitor in early-stage clinical trials. It also recently discontinued a dual PPAR agonist originally intended as a follow-up to muraglitazar.