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Blood Pressure Lowering and Sodium-Glucose Co-transporter 2 Inhibitors (SGLT2is): More Than Osmotic Diuresis

  • Hillel Sternlicht
  • George L. BakrisEmail author
Antihypertensive Agents: Mechanisms of Drug Action (Michael E. Ernst, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Antihypertensive Agents: Mechanisms of Drug Action

Abstract

Purpose of Review

This is an update of data regarding changes in blood pressure using sodium-glucose co-transporter 2 inhibitors (SGLT2i) for the treatment of diabetes. The mechanism of blood pressure lowering by SGLT2i was thought to be due to their osmotic diuretic effects. New data, however, has emerged from meta-analyses and studies of people with impaired kidney function demonstrating similar or greater magnitudes of blood pressure reduction in the absence of significant glycosuria. Potential additional mechanisms are proposed and reviewed.

Recent Findings

Two separate meta-analyses in over 10,000 participants combined demonstrate an average of 4/2 mmHg reduction in blood pressure by SGLT2i. This includes consistency between measurements of in-office and ambulatory blood pressure monitoring. This reduction extends to decreases in nocturnal blood pressure of 2.6 mmHg systolic pressure. These reductions in blood pressure by SGLT2i are also present when added to ongoing treatment with ACE inhibitors or ARBs. In one study, dapagliflozin, when added to a regimen of a renin-angiotensin-aldosterone system (RAAS) antagonist and a diuretic, further lowered in-office systolic pressure by 2.4 mmHg. In contrast, when prescribed to those on a RAAS antagonist plus a calcium channel blocker or RAAS antagonist plus a beta blocker, systolic pressure decreased 5.4 mmHg. Lastly, post hoc analyses of major cardiovascular outcome trials across the spectrum of estimated glomerular filtration rates from 30 to 80 ml/min/1.73 m2 demonstrated similar magnitudes of BP reduction in spite of far less reduction in glucosuria among those with advanced kidney disease. Moreover, recent data implicate the potential for increased ketones associated with SGLT2i contributing to blood pressure lowering in advanced-stage kidney disease.

Summary

SGLT2i are well established to lower blood pressure. Their mechanism appears to be multifactorial and has a hemodynamic as well as metabolic component contributing to this reduction.

Keywords

Hypertension Diabetes Sodium-glucose transporter 

Notes

Compliance with Ethical Standards

Conflict of Interest

Dr. Bakris reports grants from Janssen, Bayer, Vascular Dynamics, and NovoNordisk, and personal fees from Merck, outside the submitted work. Dr. Sternlicht declares no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.AHA Comprehensive Hypertension Center, Department of Medicine, Section of Endocrinology, Diabetes, and MetabolismThe University of Chicago MedicineChicagoUSA

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