Effects of high dose aleglitazar on renal function in patients with type 2 diabetes
International Journal of Cardiology, 09/07/2011
Herz M et al. – Despite the increased incidence of expected, dose–dependent peroxisome proliferator–activated receptor (PPAR) class side effects (e.g., peripheral edema, weight gain, and congestive heart failure) limiting further development of this supratherapeutic dosage of aleglitazar (600μg/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 150μg daily dose.Methods
- SESTA R was a 26–week, randomized, double–blind, multicenter study comparing the effects of a supratherapeutic dosage of aleglitazar (600μg/day) with pioglitazone (45mg/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 120ml/min/1.73m2).
- In 118 patients with evaluable GFR measurements, baseline mean (±SD) mGFR was 97.6±17.5ml/min/1.73m2 in the aleglitazar group and 101.9±21.6ml/min/1.73m2 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.