Document Detail


Examining the safety of PPAR agonists - current trends and future prospects.
MedLine Citation:
PMID:  23134541     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Introduction: 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. Areas covered: 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. Expert opinion: 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.
Authors:
Michele Bortolini; Matthew B Wright; Martin Bopst; Bogdana Balas
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-8
Journal Detail:
Title:  Expert opinion on drug safety     Volume:  -     ISSN:  1744-764X     ISO Abbreviation:  Expert Opin Drug Saf     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101163027     Medline TA:  Expert Opin Drug Saf     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
F. Hoffmann-La Roche, Ltd, PDS-Safety Risk Management , 663/2028, CH4070 Basel , Switzerland +41 61 687952 ; michele.bortolini@roche.com.
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