Effects of the dual peroxisome proliferator-activated receptor-α/γ agonist aleglitazar on renal function in patients with stage 3 chronic kidney disease and type 2 diabetes: a Phase IIb, randomized study

BACKGROUND: Type 2 diabetes is a major risk factor for chronic kidney disease, which substantially increases the risk of cardiovascular disease mortality. This Phase IIb safety study (AleNephro) in patients with stage 3 chronic kidney disease and type 2 diabetes, evaluated the renal effects of aleglitazar, a balanced peroxisome proliferator-activated receptor-α/γ agonist. METHODS: Patients were randomized to 52 weeks’ double-blind treatment with aleglitazar 150 μg/day (n = 150) or pioglitazone 45 mg/day (n = 152), followed by an 8-week off-treatment period. The primary endpoint was non-inferiority for the difference between aleglitazar and pioglitazone in percentage change in estimated glomerular filtration rate from baseline to end of follow-up. Secondary endpoints included change from baseline in estimated glomerular filtration rate and lipid profiles at end of treatment. RESULTS: Mean estimated glomerular filtration rate change from baseline to end of follow-up was –2.7% (95% confidence interval: –7.7, 2.4) with aleglitazar versus –3.4% (95% confidence interval: –8.5, 1.7) with pioglitazone, establishing non-inferiority (0.77%; 95% confidence interval: –4.5, 6.0). Aleglitazar was associated with a 15% decrease in estimated glomerular filtration rate versus 5.4% with pioglitazone at end of treatment, which plateaued to 8 weeks and was not progressive. Superior improvements in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides, with similar effects on glycosylated hemoglobin were observed with aleglitazar versus pioglitazone. No major safety concerns were identified. CONCLUSIONS: The primary endpoint in AleNephro was met, indicating that in stage 3 chronic kidney disease patients with type 2 diabetes, the decrease in estimated glomerular filtration rate after 52 weeks’ treatment with aleglitazar followed by 8 weeks off-treatment was reversible and comparable (non-inferior) to pioglitazone. TRIAL REGISTRATION: NCT01043029 January 5, 2010. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2369-15-180) contains supplementary material, which is available to authorized users.