Document Detail

Examining the safety of PPAR agonists - current trends and future prospects.
MedLine Citation:
PMID:  23134541     Owner:  NLM     Status:  MEDLINE    
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.
Michele Bortolini; Matthew B Wright; Martin Bopst; Bogdana Balas
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2012-11-08
Journal Detail:
Title:  Expert opinion on drug safety     Volume:  12     ISSN:  1744-764X     ISO Abbreviation:  Expert Opin Drug Saf     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-20     Completed Date:  2013-05-29     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101163027     Medline TA:  Expert Opin Drug Saf     Country:  England    
Other Details:
Languages:  eng     Pagination:  65-79     Citation Subset:  IM    
Cardiometabolic Franchise Safety Science Leader, F. Hoffmann-La Roche, Ltd, PDS-Safety Risk Management, 663/2028, CH4070 Basel, Switzerland.
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MeSH Terms
Cardiovascular Diseases / chemically induced
Diabetes Mellitus, Type 2 / drug therapy*,  metabolism
Drug Design
Dyslipidemias / drug therapy*,  metabolism
Hypoglycemic Agents / adverse effects,  chemistry,  therapeutic use*
Hypolipidemic Agents / adverse effects,  chemistry,  therapeutic use*
PPAR alpha / agonists*,  metabolism
PPAR gamma / agonists*,  metabolism
Risk Assessment
Risk Factors
Treatment Outcome
Urinary Bladder Neoplasms / chemically induced
Reg. No./Substance:
0/Hypoglycemic Agents; 0/Hypolipidemic Agents; 0/PPAR alpha; 0/PPAR gamma

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