title: 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.
abstract: 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.
  
  
  BACKGROUND
  NCT01043029 January 5, 2010.
authors.affiliation: Hospital 12 de Octubre, Clinical Science, Madrid, Spain. ruilope@ad-hocbox.com.
authors.forename: Luis
authors.initials: L
authors.lastname: Ruilope
authors.forename: Markolf
authors.initials: M
authors.lastname: Hanefeld
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lincoff
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Viberti
authors.forename: Sylvie
authors.initials: S
authors.lastname: Meyer-Reigner
authors.forename: Nadejda
authors.initials: N
authors.lastname: Mudie
authors.forename: Dominika
authors.initials: D
authors.lastname: Wieczorek Kirk
authors.forename: Klas
authors.initials: K
authors.lastname: Malmberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Herz
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D013810:Therapeutic Equivalency; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D000077205:Pioglitazone; D045162:Thiazolidinediones; D013876:Thiophenes; C542437:aleglitazar