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PPAR dual agonists: are they opening Pandora's Box?
Pitchai Balakumar1, Madhankumar Rose, Subrahmanya S Ganti
1Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India. pbala2006@gmail.com
Pharmacological Research
|April 13, 2007
Summary
Peroxisome proliferator activated receptors (PPARs) show promise for treating diabetic cardiovascular complications. While dual PPARalpha/gamma agonists have risks, novel PPARalpha/delta and PPAR gamma/delta agonists offer new therapeutic avenues.
Area of Science:
- Endocrinology and Metabolism
- Cardiovascular Research
- Pharmacology
Background:
- Cardiovascular disorders are the leading cause of mortality in diabetes mellitus patients.
- Current diabetes treatments do not adequately address secondary cardiovascular complications.
- Peroxisome proliferator activated receptors (PPARs) are key regulators of glucose and lipid metabolism.
Purpose of the Study:
- To critically analyze the role of PPAR agonists in managing diabetic cardiovascular complications.
- To review the protective and detrimental effects of various PPAR agonists.
- To explore novel PPAR agonist combinations for future therapeutic strategies.
Main Methods:
- Literature review of basic and clinical studies on PPAR agonists.
- Analysis of clinical trial data for PPARalpha/gamma dual agonists.
- Examination of preclinical data for PPARalpha/delta, PPAR gamma/delta, and pan-PPAR agonists.
Main Results:
- PPARalpha activation reduces triglycerides; PPARgamma activation enhances insulin sensitivity; PPARdelta activation improves fatty acid metabolism.
- PPARalpha/gamma dual agonists show potential but carry risks like cardiovascular events and carcinogenicity.
- Emerging evidence highlights the cardioprotective role of PPARdelta, supporting development of new dual and pan-agonists.
Conclusions:
- PPAR agonists represent a promising therapeutic class for diabetic cardiovascular complications.
- Development of PPARalpha/delta and PPAR gamma/delta dual agonists, and PPARalpha/gamma/delta pan agonists, may offer improved safety and efficacy.
- Further research into novel PPAR agonists is crucial for advancing the management of diabetic cardiovascular disease.
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