Effects of the sodium-glucose co-transporter 2 inhibitor dapagliflozin in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease

Nephrol Dial Transplant. 2018 Nov 1;33(11):2005-2011. doi: 10.1093/ndt/gfx350.

Abstract

Background: The sodium-glucose co-transporter 2 inhibitor dapagliflozin decreases haemoglobin A1c (HbA1c), body weight, blood pressure (BP) and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes. The efficacy and safety of this drug have not been properly defined in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease (CKD).

Methods: In a pooled analysis of 11 phase 3 randomized controlled clinical trials, we determined least square mean changes in HbA1c, body weight, BP, estimated glomerular filtration rate (eGFR) and UACR over 102 weeks in patients with type 2 diabetes and an eGFR between 12 to less than 45 mL/min/1.73 m2 receiving placebo (n = 69) or dapagliflozin 5 or 10 mg (n = 151). Effects on UACR were determined in a subgroup of patients with baseline UACR ≥30 mg/g (n = 136).

Results: Placebo-corrected changes in HbA1c with dapagliflozin 5 and 10 mg were 0.03% [95% confidence interval (CI) -0.3-0.3] and 0.03% (95% CI -0.2-0.3) during the overall 102-week period. Dapagliflozin 5 and 10 mg compared with placebo reduced UACR by - 47.1% (95% CI -64.8 to - 20.6) and -38.4% (95% CI -57.6 to - 10.3), respectively. Additionally, dapagliflozin 5 and 10 mg compared with placebo reduced BP and body weight. eGFR increased with placebo during the first 4 weeks but did not change with dapagliflozin. There were no between-group differences in eGFR at the end of follow-up. Adverse events associated with renal function occurred more frequently in the dapagliflozin 10-mg group. These events were mainly asymptomatic increases in serum creatinine.

Conclusions: Dapagliflozin did not decrease HbA1c in patients with type 2 diabetes and Stages 3b-4 CKD, but decreased UACR, BP and body weight to a clinically meaningful extent. These results support a large outcome trial in this population to confirm long-term safety and efficacy in reducing adverse clinical endpoints.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albuminuria / chemically induced
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / therapeutic use*
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Creatinine / urine
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glomerular Filtration Rate / drug effects
  • Glucosides / adverse effects
  • Glucosides / therapeutic use*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*

Substances

  • 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
  • Benzhydryl Compounds
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Creatinine