Peliglitazar

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Peliglitazar is a thiazolidinedione and fibrate dual PPAR agonist that was investigated for the treatment of type 2 diabetes mellitus. It acts as an agonist of both the peroxisome proliferator-activated receptor (PPAR) alpha and PPAR gamma subtypes. These receptors are involved in the regulation of lipid metabolism and glucose homeostasis.

Mechanism of Action

Peliglitazar functions by activating PPARα and PPARγ receptors. PPARα activation leads to increased fatty acid oxidation and improved lipid profiles, while PPARγ activation enhances insulin sensitivity and glucose uptake in adipose tissue and muscle. This dual action was intended to provide comprehensive metabolic control in patients with type 2 diabetes.

Clinical Development

Peliglitazar was developed by Bristol-Myers Squibb and underwent clinical trials to assess its efficacy and safety in managing type 2 diabetes. However, during the clinical trials, concerns about cardiovascular safety and potential hepatotoxicity led to the discontinuation of its development.

Pharmacokinetics

The pharmacokinetic profile of Peliglitazar includes its absorption, distribution, metabolism, and excretion. It is primarily metabolized in the liver and excreted via the kidneys. The half-life and bioavailability were studied during its clinical trials, but detailed data were not fully published due to the cessation of its development.

Safety and Efficacy

While Peliglitazar showed promise in improving glycemic control and lipid profiles, the safety concerns, particularly related to cardiovascular risks, outweighed the benefits. The Food and Drug Administration (FDA) and other regulatory bodies require a thorough assessment of cardiovascular outcomes for diabetes medications, which Peliglitazar did not meet satisfactorily.

Conclusion

Peliglitazar represents a class of drugs that aimed to provide dual benefits in diabetes management by targeting both lipid and glucose metabolism. Despite its potential, the safety concerns highlight the challenges in developing new therapies for complex conditions like type 2 diabetes.

Also see

• Thiazolidinedione
• Fibrate
• PPAR agonist
• Type 2 diabetes mellitus
• Insulin resistance

PPAR Agonists
Type	Example
PPAR-α	Fibrate
PPAR-γ	Thiazolidinedione
PPAR-δ	GW501516
Dual/Triple Agonists
PPAR-α/γ	Saroglitazar
PPAR-α/δ	Elafibranor
PPAR-γ/δ	Tesaglitazar
PPAR pan	Bezafibrate