Discovery and development of selective PPARγ modulators as safe and effective antidiabetic agents

Abstract

Importance of the field: PPARγ full agonists (pioglitazone and rosiglitazone) are the mainstay drugs for the treatment of type 2 diabetes; however, mechanism-based side effects have limited their full therapeutic potential. In recent years, much progress has been achieved in the discovery and development of selective PPARγ modulators (SPPARγMs) as safer alternatives to PPARγ full agonists.

Areas covered in this review: This review focuses on the preclinical and clinical data of all the SPPARγMs discovered so far, retrieved by searching PubMed, Prous Integrity database and company news updates from 1999 to date.

What the reader will gain: Here we thoroughly discuss SPPARγMs' mode of action, briefly examine new ways to identify superior SPPARγMs, and finally, compare and contrast the pharmacological and safety profile of various agents.

Take home message: The preclinical and clinical findings clearly suggest that selective PPARγ modulators have the potential to become the next generation of PPARγ agonists: effective insulin sensitizers with a superior safety profile to that of PPARγ full agonists.

Keywords::

• edema
• insulin sensitization
• PPARγ modulators
• weight gain

Acknowledgement

We are extremely thankful to M Dutta for his assistance in drawing and organizing structures using the Chew Draw. We are also highly thankful to S Sharma, R Sharma and S Bal-Tembe for reading and providing assistance with writing the manuscript.

Notes

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