Pooled analysis of Phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin

Kidney Int. 2018 Jan;93(1):231-244. doi: 10.1016/j.kint.2017.06.017. Epub 2017 Aug 30.

Abstract

Sodium glucose cotransporter 2 (SGLT2) inhibitors reduce HbA1c, blood pressure, and weight in patients with type 2 diabetes. To investigate the effect of renal function on reductions in these parameters with the SGLT2 inhibitor empagliflozin, we assessed subgroups by baseline estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease) in pooled data from five 24-week trials of 2286 patients with type 2 diabetes randomized to empagliflozin or placebo. Reductions in HbA1c with empagliflozin versus placebo significantly diminished with decreasing baseline eGFR. Reductions in systolic blood pressure (SBP) with empagliflozin were maintained in patients with lower eGFR. The mean placebo-corrected changes from baseline in systolic blood pressure at week 24 with empagliflozin were -3.2 (95% confidence interval -4.9,-1.5) mmHg, -4.0 (-5.4, -2.6) mmHg, -5.5 (-7.6, -3.4) mmHg, and -6.6 (-11.4, -1.8) mmHg in patients with an eGFR of 90 or more, 60 to 89, 30 to 59, and under 30 ml/min/1.73m2, respectively. Similar trends were observed for diastolic blood pressure. Weight loss with empagliflozin versus placebo tended to be attenuated in patients with a lower eGFR. Results were consistent in a 12-week ambulatory blood pressure monitoring trial in 823 patients with type 2 diabetes and hypertension. Thus, unlike HbA1c reductions, systolic blood pressure and weight reductions with empagliflozin are generally preserved in patients with chronic kidney disease.

Keywords: SGLT2 inhibition; diabetic nephropathy; glomerular filtration rate; kidney diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / therapeutic use*
  • Biomarkers / blood
  • Blood Pressure / drug effects*
  • Clinical Trials, Phase III as Topic
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / physiopathology*
  • Down-Regulation
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Glucosides / adverse effects
  • Glucosides / therapeutic use*
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / physiopathology*
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Treatment Outcome
  • Weight Loss / drug effects*

Substances

  • Benzhydryl Compounds
  • Biomarkers
  • Glucosides
  • Glycated Hemoglobin A
  • Sodium-Glucose Transporter 2 Inhibitors
  • hemoglobin A1c protein, human
  • empagliflozin