Effects of high dose aleglitazar on renal function in patients with type 2 diabetes.

Abstract

BACKGROUND:

Aleglitazar is a new, balanced dual peroxisome proliferator-activated receptor (PPAR)α/γ agonist designed to optimize lipid and glycemic benefits and minimize PPAR-related adverse effects.

METHODS:

SESTA R was a 26-week, randomized, double-blind, multicenter study comparing the effects of a supratherapeutic dosage of aleglitazar (600 μg/day) with pioglitazone (45 mg/day) on change in measured GFR (mGFR) in 174 patients with type 2 diabetes and normal to mildly impaired renal function (estimated GFR [eGFR] 60 to 120 ml/min/1.73 m(2)).

RESULTS:

In 118 patients with evaluable GFR measurements, baseline mean (± SD) mGFR was 97.6 ± 17.5 ml/min/1.73 m(2) in the aleglitazar group and 101.9±21.6ml/min/1.73m(2) in the pioglitazone group. Mean percent change from baseline mGFR was -16.9% (90% confidence interval -22.0 to -11.5) with aleglitazar and -4.6% (-10.15 to 1.35) with pioglitazone, a mean treatment difference of -13.0% (-19.0 to -6.5). The 17% decrease from baseline in mGFR was consistent with the 19% decrease in eGFR Modification of Diet in Renal Disease (MDRD) observed with aleglitazar, which reached a plateau after 4weeks, with no further progression until treatment discontinuation. Following aleglitazar withdrawal, eGFR values returned to pretreatment levels within the 4-8-week follow-up, which suggests reversible hemodynamic changes in renal function.

CONCLUSIONS:

Despite the increased incidence of expected, dose-dependent PPAR class side effects (e.g., peripheral edema, weight gain, and congestive heart failure) limiting further development of this supratherapeutic dosage of aleglitazar (600 μg/day), these data, together with the data from the dose-ranging SYNCHRONY study, suggest aleglitazar may be a potential new treatment for cardiovascular risk reduction in post-acute coronary syndrome patients at the therapeutic 150 μg daily dose.

• Authors: Matthias Herz, Flavio Gaspari, Norberto Perico, Giancarlo Viberti, Teresa Urbanowska, Michael Rabbia, Dominika Wieczorek Kirk
• Journal: International journal of cardiology (Int J Cardiol) Vol. 151 Issue 2 Pg. 136-42 (Sep 01 2011) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 20837369 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Oxazoles
• Thiophenes
• aleglitazar

Topics

• Adolescent
• Adult
• Aged
• Diabetes Mellitus, Type 2 (drug therapy, physiopathology)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Follow-Up Studies
• Glomerular Filtration Rate (drug effects)
• Humans
• Male
• Middle Aged
• Oxazoles (administration & dosage, adverse effects)
• Prognosis
• Renal Insufficiency (chemically induced, physiopathology)
• Retrospective Studies
• Thiophenes (administration & dosage, adverse effects)
• Young Adult