The effect of empagliflozin on muscle sympathetic nerve activity in patients with type II diabetes mellitus.

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.

• Authors: Jens Jordan, Jens Tank, Karsten Heusser, Tim Heise, Christoph Wanner, Martina Heer, Sreeraj Macha, Michaela Mattheus, Søren S Lund, Hans J Woerle, Uli C Broedl
• Journal: Journal of the American Society of Hypertension : JASH (J Am Soc Hypertens) Vol. 11 Issue 9 Pg. 604-612 (Sep 2017) ISSN: 1878-7436 [Electronic] United States
• PMID: 28757109 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2017 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Chemical References

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

Topics

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