title: The effect of dapagliflozin on renal function in patients with type 2 diabetes.
abstract: Dapagliflozin's antihyperglycemic effects are mediated by inhibition of renal sodium-glucose cotransporter-2; therefore, renal safety of dapagliflozin was assessed.
  
  
  
  Twelve double-blind, placebo-controlled, randomized clinical trials were analyzed up to 24 weeks (N = 4545). Six of the 12 studies included long-term data for up to 102 weeks (N = 3036). Patients with type 2 diabetes with normal or mildly impaired renal function [estimated glomerular filtration rate (eGFR) 60 to <90 mL/min/1.73 m(2)] were treated with dapagliflozin (2.5, 5, or 10 mg/day) or placebo. Renal adverse events (AEs) were assessed.
  
  
  
  Mean eGFR showed small transient reductions with dapagliflozin at week 1, but returned to near baseline values by week 24 and remained stable to week 102. Mean eGFR changes were not very different for dapagliflozin 2.5, 5 and 10 mg versus placebo at 102 weeks: -0.74, 2.52 and 1.38 versus 1.31 mL/min/1.73 m(2), respectively. Renal AEs were similar in frequency to placebo through 24 weeks (1.4, 1.3, 0.9, and 0.9 %, respectively) and 102 weeks (2.4, 1.8, 1.9 and 1.7 %, respectively). Few were serious (0.2, 0.1, 0 and 0.3 %, respectively, over 102 weeks). The most common renal event was serum creatinine increase. In sub-group analyses in patients ≥65 years of age or those with moderate renal impairment (eGFR 30 to <60 mL/min/1.73 m(2)), renal AEs occurred more frequently with dapagliflozin than placebo. No events of acute tubular necrosis were reported.
  
  
  
  In patients with normal or mildly impaired renal function, dapagliflozin is not associated with increased risk of acute renal toxicity or deterioration of renal function. All trials included in this analysis are registered at ClinicalTrials.gov: NCT00263276, NCT00972244, NCT00528372, NCT00736879, NCT00528879, NCT00855166, NCT00357370, NCT00680745, NCT00683878, NCT00673231, NCT00643851, NCT00859898.
authors.affiliation: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA.
authors.forename: Donald Elliott
authors.initials: DE
authors.lastname: Kohan
authors.affiliation: Department of Medicine, University of Padua, Padua, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Fioretto
authors.affiliation: Global Medical Affairs, AstraZeneca, Mölndal, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Johnsson
authors.affiliation: Global Medical Affairs, AstraZeneca, Wilmington, DE, USA.
authors.forename: Shamik
authors.initials: S
authors.lastname: Parikh
authors.affiliation: Bristol-Myers Squibb, Research and Development, Route 206 and Provinceline Road, Princeton, NJ, 08543, USA. agata.ptaszynska@bms.com.
authors.forename: Agata
authors.initials: A
authors.lastname: Ptaszynska
authors.affiliation: Bristol-Myers Squibb, Research and Development, Route 206 and Provinceline Road, Princeton, NJ, 08543, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ying
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005960:Glucosides / Q000009:adverse effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; C529054:dapagliflozin
keywords: Dapagliflozin; Renal; SGLT2; Safety