title: Efficacy and safety of canagliflozin in patients with type 2 diabetes and stage 3 nephropathy.
abstract: OBJECTIVE
  Some sodium glucose co-transporter 2 (SGLT2) inhibitors are approved for the treatment of patients with type 2 diabetes mellitus (T2DM) with an estimated glomerular filtration rate (eGFR) of ≥45 ml/min/1.73 m(2). The efficacy and safety of canagliflozin, an approved SGLT2 inhibitor, was evaluated in patients with stage 3 chronic kidney disease (CKD; eGFR ≥30 to <60 ml/min/1.73 m(2)).
  
  
  METHODS
  This analysis used integrated data from four randomized, placebo-controlled, phase 3 studies that enrolled patients with T2DM and stage 3 CKD. RESULTS are presented for the overall population as well as subgroups with stage 3a CKD (eGFR ≥45 and <60 ml/min/1.73 m(2)) and stage 3b CKD (eGFR ≥30 and <45 ml/min/1.73 m(2)).
  
  
  RESULTS
  Among all subjects studied with stage 3 CKD, placebo-subtracted reductions in HbA1c (-0.38 and -0.47%; p < 0.001), body weight (-1.6 and -1.9%; p < 0.001), and systolic blood pressure (-2.8 and -4.4 mm Hg; p < 0.01) were seen with canagliflozin 100 and 300 mg, respectively. Decreases in HbA1c, body weight, and systolic blood pressure were examined in the stage 3a and 3b CKD subgroups, with greater decreases in HbA1c, -0.47% (-0.61, -0.32) and body weight in subjects in stage 3a CKD, -1.8% (-2.3, -1.2) with canagliflozin 100 mg. Initial declines in eGFR were seen early following treatment initiation with canagliflozin, but trended towards baseline over time. The most common adverse events with canagliflozin included genital mycotic infections and adverse events related to reduced intravascular volume likely secondary to osmotic diuresis.
  
  
  CONCLUSIONS
  In subjects with T2DM and stage 3 CKD, canagliflozin reduced HbA1c, body weight, and blood pressure, and was generally well tolerated.
authors: The University of Chicago Medicine, Chicago, Ill., Janssen Research & Development, LLC, USA.
authors: Hala
authors: H
authors: Yamout
authors: Vlado
authors: V
authors: Perkovic
authors: Melanie
authors: M
authors: Davies
authors: Vincent
authors: V
authors: Woo
authors: Dick
authors: D
authors: de Zeeuw
authors: Cristiana
authors: C
authors: Mayer
authors: Ujjwala
authors: U
authors: Vijapurkar
authors: Irina
authors: I
authors: Kline
authors: Keith
authors: K
authors: Usiskin
authors: Gary
authors: G
authors: Meininger
authors: George
authors: G
authors: Bakris
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D000068896:Canagliflozin; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate; D005960:Glucosides / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000378:metabolism; D012720:Severity of Illness Index; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D000068896:Canagliflozin; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D013876:Thiophenes; C517652:hemoglobin A1c protein, human