TY - JOUR
T1 - Effects of high dose aleglitazar on renal function in patients with type 2 diabetes
AU - Herz, Matthias
AU - Gaspari, Flavio
AU - Perico, Norberto
AU - Viberti, Giancarlo
AU - Urbanowska, Teresa
AU - Rabbia, Michael
AU - Kirk, Dominika Wieczorek
PY - 2011/9/1
Y1 - 2011/9/1
N2 - Background: Aleglitazar is a new, balanced dual peroxisome proliferator-activated receptor (PPAR)alpha/gamma 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 mu g/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+/-17.5ml/min/1.73 m(2) in the aleglitazar group and 101.9+/-21.6 ml/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 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 mu g/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 mu g daily dose. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
AB - Background: Aleglitazar is a new, balanced dual peroxisome proliferator-activated receptor (PPAR)alpha/gamma 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 mu g/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+/-17.5ml/min/1.73 m(2) in the aleglitazar group and 101.9+/-21.6 ml/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 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 mu g/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 mu g daily dose. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
U2 - 10.1016/j.ijcard.2010.08.037
DO - 10.1016/j.ijcard.2010.08.037
M3 - Article
VL - 151
SP - 136
EP - 142
JO - International Journal of Cardiology
JF - International Journal of Cardiology
IS - 2
ER -
