The Effect of Empagliflozin on Muscle Sympathetic Nerve Activity in Patients With Type II Diabetes Mellitus

J Am Soc Hypertens. 2017 Sep;11(9):604-612. doi: 10.1016/j.jash.2017.07.005. Epub 2017 Jul 21.

Abstract

Inhibition of sodium glucose cotransporter 2 with empagliflozin results in caloric loss by increasing urinary glucose excretion and has a mild diuretic effect. Diuretic effects are usually associated with reflex-mediated increases in sympathetic tone, whereas caloric loss is associated with decreased sympathetic tone. In an open-label trial, muscle sympathetic nerve activity (MSNA) (burst frequency, burst incidence, and total MSNA) was assessed using microneurography performed off-treatment and on day 4 of treatment with empagliflozin 25 mg once daily in 22 metformin-treated patients with type II diabetes (mean [range] age 54 [40-65] years). Systolic and diastolic blood pressure (BP), heart rate, urine volume, and body weight were assessed before and on day 4 (BP, heart rate), day 5 (urine volume), or day 6 (body weight) of treatment with empagliflozin. After 4 days of treatment with empagliflozin, no significant changes in MSNA were apparent despite a numerical increase in urine volume, numerical reductions in BP, and significant weight loss. There were no clinically relevant changes in heart rate. Empagliflozin is not associated with clinically relevant reflex-mediated sympathetic activation in contrast to increases observed with diuretics in other studies. Our study suggests a novel mechanism through which sodium glucose cotransporter 2 inhibition affects human autonomic cardiovascular regulation.

Keywords: Blood pressure; body weight; heart rate; sodium glucose cotransporter 2 inhibition; urine volume.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Benzhydryl Compounds / pharmacology*
  • Benzhydryl Compounds / therapeutic use
  • Blood Glucose / drug effects
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / urine
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / methods
  • Female
  • Glucose / metabolism
  • Glucosides / pharmacology*
  • Glucosides / therapeutic use
  • Heart Rate / drug effects
  • Humans
  • Hypertension / physiopathology
  • Hypertension / prevention & control
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / innervation*
  • Renal Elimination / drug effects
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Sympathetic Nervous System / drug effects*
  • Sympathetic Nervous System / physiopathology

Substances

  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Hypoglycemic Agents
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Metformin
  • empagliflozin
  • Glucose