Send to

Choose Destination
Expert Opin Drug Saf. 2013 Jan;12(1):65-79. doi: 10.1517/14740338.2013.741585. Epub 2012 Nov 8.

Examining the safety of PPAR agonists - current trends and future prospects.

Author information

Cardiometabolic Franchise Safety Science Leader, F. Hoffmann-La Roche, Ltd, PDS-Safety Risk Management, 663/2028, CH4070 Basel, Switzerland.



The peroxisome proliferator-activated receptor (PPAR)-α and -γ agonists, fibrates and glitazones, are effective treatments for dyslipidemia and type 2 diabetes mellitus, respectively, but exhibit class-related, as well as compound-specific safety characteristics.


This article reviews the profiles of PPAR-α, PPAR-γ, and dual PPAR-α/γ agonists with regard to class-related and compound-specific efficacy and adverse effects. We explore how learnings from first-generation drugs are being applied to develop safer PPAR-targeted therapies.


The finding that rosiglitazone may increase risk for cardiovascular events has led to regulatory guidelines requiring demonstration of cardiovascular safety in appropriate outcome trials for new type 2 diabetes mellitus drugs. The emerging data on the possibly increased risk of bladder cancer with pioglitazone may prompt the need for post-approval safety studies for new drugs. Since PPAR-α and -γ affect key cardiometabolic risk factors (diabetic dyslipidemia, insulin resistance, hyperglycemia, and inflammation) in a complementary fashion, combining their benefits has emerged as a particularly attractive option. New PPAR-targeted therapies that balance the relative potency and/or activity toward PPAR-α and -γ have shown promise in retaining efficacy while reducing potential side effects.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center