Hillel Sternlicht1, George L Bakris2. 1. AHA Comprehensive Hypertension Center, Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, The University of Chicago Medicine, 5841 S. Maryland Ave. MC 1027, Chicago, IL, 60637, USA. 2. AHA Comprehensive Hypertension Center, Department of Medicine, Section of Endocrinology, Diabetes, and Metabolism, The University of Chicago Medicine, 5841 S. Maryland Ave. MC 1027, Chicago, IL, 60637, USA. gbakris@uchicago.edu.
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. 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.
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. 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.
Authors: Meg J Jardine; Zien Zhou; Kenneth W Mahaffey; Megumi Oshima; Rajiv Agarwal; George Bakris; Harpreet S Bajaj; Scott Bull; Christopher P Cannon; David M Charytan; Dick de Zeeuw; Gian Luca Di Tanna; Tom Greene; Hiddo J L Heerspink; Adeera Levin; Bruce Neal; Carol Pollock; Rose Qiu; Tao Sun; David C Wheeler; Hong Zhang; Bernard Zinman; Norman Rosenthal; Vlado Perkovic Journal: J Am Soc Nephrol Date: 2020-05 Impact factor: 10.121
Authors: Yuling Yan; Bin Liu; Jun Du; Jing Wang; Xiaodong Jing; Yajie Liu; Songbai Deng; Jianlin Du; Qiang She Journal: ESC Heart Fail Date: 2021-03-21
Authors: George Bakris; Megumi Oshima; Kenneth W Mahaffey; Rajiv Agarwal; Christopher P Cannon; George Capuano; David M Charytan; Dick de Zeeuw; Robert Edwards; Tom Greene; Hiddo J L Heerspink; Adeera Levin; Bruce Neal; Richard Oh; Carol Pollock; Norman Rosenthal; David C Wheeler; Hong Zhang; Bernard Zinman; Meg J Jardine; Vlado Perkovic Journal: Clin J Am Soc Nephrol Date: 2020-11-19 Impact factor: 8.237