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

Matthias Herz, Flavio Gaspari, Norberto Perico, Giancarlo Viberti, Teresa Urbanowska, Michael Rabbia, Dominika Wieczorek Kirk

Research output: Contribution to journalArticlepeer-review

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 ± 21.6 ml/min/1.73 m 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 4 weeks, 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.

Original languageEnglish
Pages (from-to)136-142
Number of pages7
JournalInternational Journal of Cardiology
Volume151
Issue number2
DOIs
Publication statusPublished - Sep 1 2011

Keywords

  • Acute coronary syndrome
  • Cardiovascular risk
  • Diabetes
  • Peroxisome proliferator-activated receptor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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