Document Detail


Aleglitazar, a dual PPARα and PPARγ agonist for the potential oral treatment of type 2 diabetes mellitus.
MedLine Citation:
PMID:  21046527     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
PPARγ and PPARα are nuclear receptors mainly involved in the regulation of glucose homeostasis and lipid levels, respectively. Aleglitazar, being developed by Roche Holding, is a dual agonist for PPARγ and PPARα for the potential simultaneous treatment of hyperglycemia and dyslipidemia in patients with type 2 diabetes mellitus (T2DM). In preclinical studies, aleglitazar decreased non-fasted glucose levels, increased glucose clearance and improved insulin resistance, while also increasing HDL-cholesterol and decreasing LDL-cholesterol levels in serum. In phase I and II clinical trials in patients with T2DM, aleglitazar demonstrated beneficial antidiabetic activities and had a higher antihyperglycemic efficacy than pioglitazone (a PPARγ agonist). Aleglitazar improved the lipid profile in patients and decreased levels of cardiovascular markers of inflammation and clotting. The observed adverse events were characteristic of either PPARγ or PPARα agonists; however, when compared to pioglitazone-PPARγ-mediated effects, such as edema and weight gain, these were less severe. PPARγ-mediated adverse events on bone have not been measured and should be addressed in the future. The PPARα-mediated adverse effects on renal function are of concern and are a primary endpoint of ongoing phase II clinical trials in patients with T2DM. A phase III clinical trial was also ongoing in patients with T2DM who had recently experienced a cardiac event.
Authors:
Beata Lecka-Czernik
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  IDrugs : the investigational drugs journal     Volume:  13     ISSN:  2040-3410     ISO Abbreviation:  IDrugs     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883655     Medline TA:  IDrugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  793-801     Citation Subset:  IM    
Affiliation:
University of Toledo, College of Medicine, Department of Orthopaedic Surgery, 3000 Arlington Avenue, Toledo, OH 43614, USA. beata.leckaczernik@utoledo.edu
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