Literature DB >> 28299616

Promise of SGLT2 Inhibitors in Heart Failure: Diabetes and Beyond.

Pieter Martens1,2, Chantal Mathieu3, Frederik H Verbrugge4.   

Abstract

OPINION STATEMENT: This review provides mechanistic insight in the pleiotropic effects of sodium-glucose transporter-2 (SGLT-2) inhibitors with particular interest to the pathophysiology of heart failure. The SGLT-2 inhibitor empagliflozin has recently demonstrated an unprecedented 38% reduction in cardiovascular mortality in patients with diabetes. Despite modest effects on long-term glycemic control, highly significant reductions in heart failure admissions and end-stage kidney disease were observed. SGLT-2 inhibitors are the latest approved class of glucose-lowering agents. By blocking sodium/glucose uptake in the proximal tubules of the nephron, they induce glycosuria. Treatment with SGLT-2 inhibitors in diabetes leads to a sustained ∼1% reduction in glycated hemoglobin levels, with favorable reductions in both arterial blood pressure (∼3-6 mmHg) and body weight (∼2-4 kg/m2). However, those effects fail to explain fully the dramatic reduction in cardiovascular mortality, heart failure readmissions, and end-stage kidney disease. The unique pharmacological profile of SGLT-2 inhibitors puts them at the crossroads of important hemodynamic, neurohumoral, metabolic, and vascular endothelial pathways influencing cardiac and renal disease. SGLT-2 inhibitors decrease proximal tubular sodium and chloride reabsorption, leading to a reset of the tubuloglomerular feedback. This induces plasma volume contraction without activation of the sympathetic nerve system, decreases harmful glomerular hyper-filtration leading to better long-term renal preservation, and improves diuretic and natriuretic responses to other diuretic agents. Moreover, SGLT-2 inhibitors might improve the efficiency of myocardial energetics by offering β-hydroxybutyrate as an attractive fuel for oxidation and increase hematocrit improving oxygen transport. Finally, decreased vascular stiffness and improved endothelial function are observed with the use of SGLT-2 inhibitors in diabetes. Those multiple nonglycemic effects reinforce SGLT-2 inhibitors as the preferred glucose-lowering drug to treat diabetic patients with heart failure. In the future, they might even be considered in heart failure or chronic kidney disease patients without diabetes.

Entities:  

Keywords:  Diabetes mellitus; Energy metabolism; Glomerular filtration rate; Heart failure; Plasma volume; Sodium-glucose transporter 2

Year:  2017        PMID: 28299616     DOI: 10.1007/s11936-017-0522-x

Source DB:  PubMed          Journal:  Curr Treat Options Cardiovasc Med        ISSN: 1092-8464


  65 in total

1.  Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.

Authors:  Benjamin M Scirica; Deepak L Bhatt; Eugene Braunwald; P Gabriel Steg; Jaime Davidson; Boaz Hirshberg; Peter Ohman; Robert Frederich; Stephen D Wiviott; Elaine B Hoffman; Matthew A Cavender; Jacob A Udell; Nihar R Desai; Ofri Mosenzon; Darren K McGuire; Kausik K Ray; Lawrence A Leiter; Itamar Raz
Journal:  N Engl J Med       Date:  2013-09-02       Impact factor: 91.245

2.  Timing of hemoconcentration during treatment of acute decompensated heart failure and subsequent survival: importance of sustained decongestion.

Authors:  Jeffrey M Testani; Meredith A Brisco; Jennifer Chen; Brian D McCauley; Chirag R Parikh; W H Wilson Tang
Journal:  J Am Coll Cardiol       Date:  2013-06-07       Impact factor: 24.094

3.  Efficacy and safety of sodium glucose co-transport-2 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials.

Authors:  M Monami; C Nardini; E Mannucci
Journal:  Diabetes Obes Metab       Date:  2013-12-29       Impact factor: 6.577

4.  Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor.

Authors:  Tadahiro Shimazu; Matthew D Hirschey; John Newman; Wenjuan He; Kotaro Shirakawa; Natacha Le Moan; Carrie A Grueter; Hyungwook Lim; Laura R Saunders; Robert D Stevens; Christopher B Newgard; Robert V Farese; Rafael de Cabo; Scott Ulrich; Katerina Akassoglou; Eric Verdin
Journal:  Science       Date:  2012-12-06       Impact factor: 47.728

5.  Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial.

Authors:  Michel Komajda; John J V McMurray; Henning Beck-Nielsen; Ramon Gomis; Markolf Hanefeld; Stuart J Pocock; Paula S Curtis; Nigel P Jones; Philip D Home
Journal:  Eur Heart J       Date:  2010-01-29       Impact factor: 29.983

6.  CV Protection in the EMPA-REG OUTCOME Trial: A "Thrifty Substrate" Hypothesis.

Authors:  Ele Ferrannini; Michael Mark; Eric Mayoux
Journal:  Diabetes Care       Date:  2016-07       Impact factor: 19.112

7.  SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice.

Authors:  Volker Vallon; Maria Gerasimova; Michael A Rose; Takahiro Masuda; Joseph Satriano; Eric Mayoux; Hermann Koepsell; Scott C Thomson; Timo Rieg
Journal:  Am J Physiol Renal Physiol       Date:  2013-11-13

8.  Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause mortality: cohort study in primary care.

Authors:  Julia Hippisley-Cox; Carol Coupland
Journal:  BMJ       Date:  2016-07-12

9.  The effect of direct renin inhibition alone and in combination with ACE inhibition on endothelial function, arterial stiffness, and renal function in type 1 diabetes.

Authors:  David Z I Cherney; James W Scholey; Shan Jiang; Ronnie Har; Vesta Lai; Etienne B Sochett; Heather N Reich
Journal:  Diabetes Care       Date:  2012-07-26       Impact factor: 19.112

10.  Effect of Acetazolamide on Obesity-Induced Glomerular Hyperfiltration: A Randomized Controlled Trial.

Authors:  Boris Zingerman; Michal Herman-Edelstein; Arie Erman; Sarit Bar Sheshet Itach; Yaacov Ori; Benaya Rozen-Zvi; Uzi Gafter; Avry Chagnac
Journal:  PLoS One       Date:  2015-09-14       Impact factor: 3.240

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  29 in total

1.  Loop diuretic use among patients with heart failure and type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors.

Authors:  Erin R Weeda; Christy Cassarly; Daniel L Brinton; David W Shirley; Kit N Simpson
Journal:  J Diabetes Complications       Date:  2019-05-10       Impact factor: 2.852

Review 2.  Direct cardiovascular impact of SGLT2 inhibitors: mechanisms and effects.

Authors:  Abdullah Kaplan; Emna Abidi; Ahmed El-Yazbi; Ali Eid; George W Booz; Fouad A Zouein
Journal:  Heart Fail Rev       Date:  2018-05       Impact factor: 4.214

Review 3.  Mitochondrial dysfunction in pathophysiology of heart failure.

Authors:  Bo Zhou; Rong Tian
Journal:  J Clin Invest       Date:  2018-08-20       Impact factor: 14.808

Review 4.  Clinical impact of oral antidiabetic medications in heart failure patients.

Authors:  Alberto Palazzuoli; Elena Ceccarelli; Gaetano Ruocco; Ranuccio Nuti
Journal:  Heart Fail Rev       Date:  2018-05       Impact factor: 4.214

Review 5.  Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials.

Authors:  Yuliya Lytvyn; Petter Bjornstad; Jacob A Udell; Julie A Lovshin; David Z I Cherney
Journal:  Circulation       Date:  2017-10-24       Impact factor: 29.690

6.  Inhibition of sodium-glucose cotransporter-2 preserves cardiac function during regional myocardial ischemia independent of alterations in myocardial substrate utilization.

Authors:  Hana E Baker; Alexander M Kiel; Samuel T Luebbe; Blake R Simon; Conner C Earl; Ajit Regmi; William C Roell; Kieren J Mather; Johnathan D Tune; Adam G Goodwill
Journal:  Basic Res Cardiol       Date:  2019-04-19       Impact factor: 17.165

Review 7.  Beyond the myocardium? SGLT2 inhibitors target peripheral components of reduced oxygen flux in the diabetic patient with heart failure with preserved ejection fraction.

Authors:  Mouhamed Nashawi; Omar Sheikh; Ayman Battisha; Mahnoor Mir; Robert Chilton
Journal:  Heart Fail Rev       Date:  2022-01       Impact factor: 4.214

8.  Heart failure hospitalization risk associated with use of two classes of oral antidiabetic medications: an observational, real-world analysis.

Authors:  Santosh Gautam; Abiy Agiro; John Barron; Thomas Power; Harry Weisman; Jeff White
Journal:  Cardiovasc Diabetol       Date:  2017-07-31       Impact factor: 9.951

Review 9.  How to tackle congestion in acute heart failure.

Authors:  Pieter Martens; Wilfried Mullens
Journal:  Korean J Intern Med       Date:  2018-04-11       Impact factor: 2.884

Review 10.  Targeting Obesity and Diabetes to Treat Heart Failure with Preserved Ejection Fraction.

Authors:  Raffaele Altara; Mauro Giordano; Einar S Nordén; Alessandro Cataliotti; Mazen Kurdi; Saeed N Bajestani; George W Booz
Journal:  Front Endocrinol (Lausanne)       Date:  2017-07-17       Impact factor: 5.555

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