Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis

Diabetes, Obesity and Metabolism

Volumn 20, Issue 3, 2018, Pages 479-487

  Hallow, Karen M ^a,b   Helmlinger, Gabriel ^c   Greasley, Peter J ^d   McMurray, John J V ^e   Boulton, David W ^c  

^a University of Georgia   (United States)

^b UNIVERSITY OF GEORGIA   (United States)

^c ASTRAZENECA   (United Kingdom)

^d ASTRAZENECA R AND D   (Sweden)

^e UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

antidiabetic drug; cardiovascular disease; dapagliflozin; diabetes complications; renal glucose handling; SGLT2 inhibitor

Indexed keywords

BUMETANIDE; DAPAGLIFLOZIN; SODIUM; 2-(3-(4-ETHOXYBENZYL)-4-CHLOROPHENYL)-6-HYDROXYMETHYLTETRAHYDRO-2H-PYRAN-3,4,5-TRIOL; BENZHYDRYL DERIVATIVE; DIURETIC AGENT; GLUCOSIDE;

ADULT; ARTERY PERFUSION; BLOOD VOLUME; CONTROLLED STUDY; DIURESIS; DRUG EFFECT; FEMALE; FREE WATER CLEARANCE; HEART FAILURE; HEART OUTPUT; HOSPITALIZATION; HUMAN; HUMAN EXPERIMENT; INTERSTITIAL FLUID; MALE; NORMAL HUMAN; OSMOSIS; PREDICTION; REVIEW; SODIUM BLOOD LEVEL; SODIUM EXCRETION; SODIUM URINE LEVEL; ADMINISTRATION AND DOSAGE; DRUG COMBINATION; DRUG INTERACTION; METABOLIC DISORDER; MIDDLE AGED; OSMOLARITY; PATHOPHYSIOLOGY; PHARMACOLOGY; RANDOMIZED CONTROLLED TRIAL; STATISTICS AND NUMERICAL DATA; URINE; YOUNG ADULT;

ADULT; BENZHYDRYL COMPOUNDS; BLOOD VOLUME; BUMETANIDE; DIURESIS; DIURETICS; DRUG COMBINATIONS; DRUG INTERACTIONS; FEMALE; GLUCOSIDES; HEART FAILURE; HOSPITALIZATION; HUMANS; MALE; MIDDLE AGED; OSMOLAR CONCENTRATION; SODIUM; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS; WATER-ELECTROLYTE IMBALANCE; YOUNG ADULT;

EID: 85034093732     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.13126     Document Type: Review

References (23)

1. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–2128.
2. Fitchett D, Zinman B, Wanner C, et al. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME(R) trial. Eur Heart J. 2016;37:1526–1534.
3. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644–657.
4. Ferrannini E, Mark M, Mayoux E. CV protection in the EMPA-REG OUTCOME Trial: a "thrifty substrate" hypothesis. Diabetes Care. 2016;39:1108–1114.
5. Shimizu K, Kurosawa T, Sanjo T, Hoshino M, Nonaka T. Solute-free versus electrolyte-free water clearance in the analysis of osmoregulation. Nephron. 2002;91:51–57.
6. Lindner G, Schwarz C, Funk GC. Osmotic diuresis due to urea as the cause of hypernatraemia in critically ill patients. Nephrol Dial Transplant. 2012;27:962–967.
7. Titze J. Water-free sodium accumulation. Semin Dial. 2009;22:253–255.
8. Hammon M, Grossmann S, Linz P, et al. 23Na Magnetic resonance imaging of the lower leg of acute heart failure patients during diuretic treatment. PLoS One. 2015;10:e0141336.
9. Titze J. Sodium balance is not just a renal affair. Curr Opin Nephrol Hypertens. 2014;23:101–105.
10. Schmieder R, Ott C, Linz P, et al. Os 12-03 Sglt-2-inhibition with Dapagliflozin reduces tissue sodium content. J Hypertens. 2016;34(suppl 1):e76.
11. Schrier RW. Body fluid volume regulation in health and disease: a unifying hypothesis. Ann Intern Med. 1990;113:155–159.
12. Schrier RW. Decreased effective blood volume in edematous disorders: what does this mean? J Am Soc Nephrol. 2007;18:2028–2031.
13. De Vecchis R, Ariano C, Esposito C, Giasi A, Cioppa C, Cantatrione S. In right or biventricular chronic heart failure addition of thiazides to loop diuretics to achieve a sequential blockade of the nephron is associated with increased risk of dilutional hyponatremia: results of a case-control study. Minerva Cardioangiol. 2012;60:517–529.
14. Francis GS, Siegel RM, Goldsmith SR, Olivari MT, Levine TB, Cohn JN. Acute vasoconstrictor response to intravenous furosemide in patients with chronic congestive heart failure. Activation of the neurohumoral axis. Ann Intern Med. 1985;103:1–6.
15. Weinfeld MS, Chertow GM, Stevenson LW. Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure. Am Heart J. 1999;138:285–290.
16. Greenberg A. Diuretic complications. Am J Med Sci. 2000;319:10–24.
17. Rabe EF. Relationship between absolute body-fluid deficits and fluid intake in the rat. J Comp Physiol Psychol. 1975;89:468–477.
18. Titze J, Luft FC, Bauer K, et al. Extrarenal Na+ balance, volume, and blood pressure homeostasis in intact and ovariectomized deoxycorticosterone-acetate salt rats. Hypertension. 2006;47:1101–1107.
19. Peacock WF, Costanzo MR, de Marco T, et al. Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry. Cardiology. 2009;113:12–19.
20. Heise T, Jordan J, Wanner C, et al. Pharmacodynamic effects of single and multiple doses of Empagliflozin in patients with type 2 diabetes. Clin Ther. 2016;38:2265–2276.
21. Heise T, Jordan J, Wanner C, et al. Acute pharmacodynamic effects of empagliflozin with and without diuretic agents in patients with type 2 diabetes mellitus. Clin Ther. 2016;38:2248–2264.e5.
22. Schneider MP, Raff U, Kopp C, et al. Skin sodium concentration correlates with left ventricular hypertrophy in CKD. J Am Soc Nephrol. 2017;28:1867–1876.
23. Hirose S, Nakajima S, Iwahashi Y, Seo A, Takahashi T, Tamori Y. Impact of the 8-week Administration of Tofogliflozin for glycemic control and body composition in Japanese Patients with type 2 diabetes mellitus. Intern Med. 2016;55:3239–3245.