Muraglitazar
Muraglitazar is a peroxisome proliferator-activated receptor (PPAR) agonist that was developed for the treatment of type 2 diabetes. It was designed to activate both PPAR-alpha and PPAR-gamma receptors, which are involved in glucose metabolism and lipid metabolism, respectively. However, the drug was withdrawn from development due to concerns about its safety profile.
History
Muraglitazar was developed by Bristol-Myers Squibb in the early 2000s. It was one of several dual PPAR agonists being developed at the time, which were hoped to provide better glucose control and lipid-lowering effects than the existing thiazolidinedione class of drugs. However, in 2006, Bristol-Myers Squibb announced that it was discontinuing development of muraglitazar due to concerns about its safety profile.
Mechanism of Action
Muraglitazar acts as a dual PPAR agonist, activating both PPAR-alpha and PPAR-gamma receptors. PPAR-alpha receptors are primarily involved in lipid metabolism, and their activation can lead to reductions in triglyceride levels and increases in high-density lipoprotein (HDL) cholesterol. PPAR-gamma receptors, on the other hand, are involved in glucose metabolism, and their activation can improve insulin sensitivity and reduce blood glucose levels.
Safety Concerns
The safety concerns that led to the discontinuation of muraglitazar primarily related to an increased risk of cardiovascular disease. In a meta-analysis of clinical trial data, muraglitazar was found to be associated with a significant increase in the risk of major adverse cardiovascular events, including heart attack and stroke. This led to the decision by Bristol-Myers Squibb to discontinue development of the drug.
See Also
Muraglitazar
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