Pharmacodynamic Effects of Single and Multiple Doses of Empagliflozin in Patients With Type 2 Diabetes

Clin Ther. 2016 Oct;38(10):2265-2276. doi: 10.1016/j.clinthera.2016.09.001. Epub 2016 Sep 28.

Abstract

Purpose: Our aim was to investigate the effects of the sodium glucose cotransporter 2 inhibitor empagliflozin on urinary and serum glucose and electrolytes, urinary volume, osmolality, and the renin-angiotensin system in patients with type 2 diabetes.

Methods: In an open-label study, 22 patients receiving metformin (median age 56 years; range 40-65 years) received empagliflozin 25 mg once daily for 5 days. Food, fluid, and sodium intake were standardized for 3 days before and during treatment.

Findings: Twenty patients completed treatment. After single and multiple doses of empagliflozin, mean (SE) changes from baseline in 24-hour urinary glucose excretion were 463.3 (57.3) mmol/d and 599.5 (60.0) mmol/d, respectively (83.5 [10.3] g/d and 108.0 [10.8] g/d, respectively) (both P < 0.001), and in fasting serum glucose concentration were -1.8 (0.4) mmol/L and -1.1 (0.3) mmol/L, respectively (both P < 0.001). After a single dose, mean (SE) change from baseline in urine sodium excretion was 45.3 (9.6) mmol/d (P < 0.001), and in urine volume was 341.0 (140.5) g/d (P = 0.025), but there were no changes compared with baseline in either parameter after multiple doses. There were no changes in plasma renin or serum aldosterone with single or multiple doses of empagliflozin. There was a nonsignificant reduction in weight after a single dose of empagliflozin and a mean (SE) change of -1.4 (0.5) kg after multiple doses (P = 0.020).

Implications: Empagliflozin 25 mg increased urinary glucose excretion and decreased serum glucose and weight with transient natriuresis and increases in urine volume, without significant changes in the renin-angiotensin system. Clinicaltrials.gov Identifier: NCT01276288.

Keywords: electrolytes; natriuresis; pharmacodynamics.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Benzhydryl Compounds / administration & dosage*
  • Blood Glucose / drug effects
  • Body Weight
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Fasting
  • Female
  • Glucosides / administration & dosage*
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Renin-Angiotensin System / drug effects
  • Sodium-Glucose Transporter 2 Inhibitors*

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Metformin
  • empagliflozin

Associated data

  • ClinicalTrials.gov/NCT01276288