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

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• 作者：Matthias Herz^a ; ^{matthias.herz@roche.com} ; Flavio Gaspari^b ; Norberto Perico^b ; Giancarlo Viberti^c ; Teresa Urbanowska^a ; Michael Rabbia^d ; Dominika Wieczorek Kirk^a
• 关键词：Peroxisome proliferator-activated receptor ; Acute coronary syndrome ; Diabetes ; Cardiovascular risk
• 刊名：International Journal of Cardiology
• 出版年：2011
• 出版时间：1 September, 2011
• 年：2011
• 卷：151
• 期：2
• 页码：136-142
• 全文大小：1K

文摘

Background

Aleglitazar is a new, balanced dual peroxisome proliferator-activated receptor (PPAR)¦Á/¦Ã 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 ¦Ìg/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 m²).

Results

In 118 patients with evaluable GFR measurements, baseline mean (¡À SD) mGFR was 97.6 ¡À 17.5 ml/min/1.73 m² in the aleglitazar group and 101.9 ¡À 21.6 ml/min/1.73 m² in the pioglitazone group. Mean percent change from baseline mGFR was ?6.9 % (90 % confidence interval ?2.0 to ?1.5) with aleglitazar and ?.6 % (?0.15 to 1.35) with pioglitazone, a mean treatment difference of ?3.0 % (?9.0 to ?.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 ¦Ìg/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 ¦Ìg daily dose.