Muraglitazar (proposed tradename Pargluva) is a dual peroxisome proliferator-activated receptor agonist with affinity to PPARα and PPARγ.[1]
The drug had completed phase III clinical trials,[2] however in May 2006 Bristol-Myers Squibb announced that it had discontinued further development.[3]
Data on muraglitazar is relatively sparse due to the brief introduction and subsequent abandonment of this agent. One double-blind randomized clinical trial comparing muraglitazar and pioglitazone found that the effects of the former were favourable in terms of HDL-C increase, decrease in total cholesterol, apolipoprotein B, triglycerides and a greater reduction in HbA1c (p <0.0001 for all comparisons). However, the muraglitazar group had a higher all-cause mortality, greater incidence of edema and heart failure and more weight gain compared to the pioglitazone group. A meta-analysis of the phase II and III clinical trials of muraglitazar revealed that it was associated with a greater incidence of myocardial infarction, stroke, transient ischemic attacks and congestive heart failure (CHF) when compared to placebo or pioglitazone.[4]
By calling attention to adverse events made public through the FDA advisory committee process, Dr Nissen came upon a mechanism to steer FDA from the outside. This mechanism came to fruition with rosiglitazone (Avandia) and led to FDA requiring demonstration of cardiac safety for new drugs to treat type 2 diabetes. This process is described by Dr Robert Misbin in INSULIN-History from an FDA Insider, published June 1, 2020 on Amazon.