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Mechanisms and prediction of short-term natriuretic effect of sodium-glucose cotransporter 2 inhibitor in heart failure patients coexisting type 2 diabetes mellitus

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Abstract

The mechanisms of the diuretic effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor and its predictors in heart failure (HF) patients with coexisting type 2 diabetes mellitus (T2DM) remain under investigation. A total of 40 hospitalized HF patients with T2DM (68 ± 13 years old, male gender 63%) were prospectively enrolled and received ipragliflozin at a dose of 50 mg once daily after breakfast for at least 4 consecutive days. They underwent first-morning blood and urine tests, and 24-h urine tests before and after short-term ipragliflozin therapy. Daily urine volume significantly increased from 1365 ± 511 mL/day on day 0 to 1698 ± 595 mL/day on day 3 (P < 0.001), which resulted in significant decreases in body weight and plasma brain natriuretic peptide level. Changes in 24-h urine volume were strongly and independently correlated with changes in 24-h urine sodium excretion (r = 0.80, P < 0.001), but was not significantly correlated with those in 24-h urine sugar excretion (r = 0.29, P = 0.07). Lower concentration of first-morning urine sodium and higher loop diuretic dosage before ipragliflozin therapy were associated with urine volume increment with ipragliflozin therapy, and former retained its independent predictor (Odds ratio 0.96, 95% CI 0.93–0.99, P = 0.02). First-morning urine sodium ≤ 53 mEq/L and baseline loop diuretics ≥ 20 mg/day predicted increased urine volume on day 3 with high diagnostic accuracy. Ipragliflozin has acute natriuretic activity, and first-morning urine sodium and baseline dosage of loop diuretics strongly predicted the diuretic effects. Ipragliflozin therapy may restore responsiveness to loop diuretics in symptomatic HF patients with T2DM.

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References

  1. Bauters C, Lamblin N, Mc Fadden EP, Van Belle E, Millaire A, de Groote P (2003) Influence of diabetes mellitus on heart failure risk and outcome. Cardiovasc Diabetol 2:1

    Article  Google Scholar 

  2. MacDonald MR, Petrie MC, Varyani F, Ostergren J, Michelson EL, Young JB, Solomon SD, Granger CB, Swedberg K, Yusuf S, Pfeffer MA, McMurray JJ, CHARM investigators (2008) Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur Heart J 29:1377–1385

    Article  Google Scholar 

  3. Gustafsson I, Brendorp B, Seibaek M, Burchardt H, Hidebrandt P, Køber L, Torp-Pedersen C, Danish Investigatord of Arrhythmia, and Mortality on Dofetilde Study Group (2004) Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure. J Am Coll Cardiol 43:771–777

    Article  Google Scholar 

  4. Marx N, McGuire DK (2016) Sodium-glucose cotransporter-2 inhibition for the reduction of cardiovascular events in high-risk patients with diabetes mellitus. Eur Heart J 37:3192–3200

    Article  CAS  Google Scholar 

  5. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE, EMPA-REG OUTCOME Investigators (2015) Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373:2117–2128

    Article  CAS  Google Scholar 

  6. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw Q, Law G, Desai M, Matthews DR, CANVAS Program Collaborative Group (2017) Canagliflozin and cardiovascular and renal events in Type 2 diabetes. N Engl J Med 377:644–657

    Article  CAS  Google Scholar 

  7. Wiviott SD, Raz I, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniler TA, Kruder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Langkilde AM, Sabatine MS, DECLARE-TIMI 58 Investigators (2019) Dapagliflozin and cardiovascular outcomes in Type 2 diabetes. N Engl J Med 380:347–357

    Article  CAS  Google Scholar 

  8. Davies MJ, D'Alessio DA, Fradkin J, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB (2018) Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 61:2461–2498

    Article  Google Scholar 

  9. Lambers Heerspink HJ, de Zeeuw D, Wie L, Leslie B, List J (2013) Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab 15:853–862

    Article  CAS  Google Scholar 

  10. Masuda T, Watanabe Y, Fukuda K, Watanabe M, Onishi A, Ohara K, Imai T, Koepsell H, Muto S, Vallon V, Nagata D (2018) Unmasking a sustained negative effect of SGLT2 inhibition on body fluid volume in the rat. Am J Physiol Renal Physiol 315:F653–664

    Article  CAS  Google Scholar 

  11. Sano M (2018) A new class of drugs for heart failure: SGLT2 inhibitors reduce sympathetic overactivity. J Cardiol 71:471–476

    Article  Google Scholar 

  12. Takeuchi T, Dohi K, Omori T, Moriwaki K, Sato Y, Nakamori S, Fujimoto N, Fujii E, Yamada N, Ito M (2015) Diuretic effects of sodium-glucose cotransporter 2 inhibitor in patients with type 2 diabetes mellitus and heart failure. Int J Cardiol 201:1–3

    Article  Google Scholar 

  13. Kimura G (2016) Diuretic action of sodium–glucose cotransporter 2 inhibitors and its importance in the management of heart failure. Circ J 80:2277–2281

    Article  CAS  Google Scholar 

  14. Imai E, Horino M, Nitta K, Yamagata K, Iseki K, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S (2007) Modification of the modification of diet in renal disease (MDRD) study equation for Japan. Am J Kidney Dis 50:927–937

    Article  Google Scholar 

  15. Dohi K, Ito M (2014) Novel diuretic strategies for the treatment of heart failure in Japan. Circ J 78:1816–1823

    Article  Google Scholar 

  16. Cherney DZ, Perkins BA, Soleymanlou N (2014) Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 129:587–597

    Article  CAS  Google Scholar 

  17. Tanaka H, Takano K, Iijima H, Kubo H, Maruyama N, Hashimoto T, Arakawa K, Togo M, Inagaki N, Kaku K (2017) Factors affecting canagliflozin-induced transient urine volume increase in patients with type 2 diabetes mellitus. Adv Ther 34:436–451

    Article  CAS  Google Scholar 

  18. Itcho K, Oki K, Kobuke K, Ohno H, Yoneda M, Hattori N (2019) Angiotensin 1–7 suppresses angiotensin II mediated aldosterone production via JAK/STAT signaling inhibition. J Steroid Biochem Mol Biol 185:137–141

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Japan

    Shusuke Fukuoka, Kaoru Dohi, Keishi Moriwaki, Masaki Ishiyama, Taku Omori & Naoki Fujimoto

  2. Department of Cardiology, Mie Chuo Medical Center, Tsu, Japan

    Tetsushiro Takeuchi

Authors
  1. Shusuke Fukuoka
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  2. Kaoru Dohi
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  3. Tetsushiro Takeuchi
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  4. Keishi Moriwaki
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  5. Masaki Ishiyama
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  6. Taku Omori
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  7. Naoki Fujimoto
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  8. Masaaki Ito
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Corresponding author

Correspondence to Kaoru Dohi.

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Conflict of interest

M. Ito received departmental research grant support equal to or more than 1,000,000 yen from Otsuka Pharmaceutical Co., Ltd. and Daiichi Sankyo Company Limited in 2018. K.D. lecture fees equal to or more than 500,000 yen from Otsuka Pharmaceutical Co., Ltd. and Takeda Pharmaceutical Company Limited in 2018. All of the other authors have no conflict of interest to this study.

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Fukuoka, S., Dohi, K., Takeuchi, T. et al. Mechanisms and prediction of short-term natriuretic effect of sodium-glucose cotransporter 2 inhibitor in heart failure patients coexisting type 2 diabetes mellitus. Heart Vessels 35, 1218–1226 (2020). https://doi.org/10.1007/s00380-020-01597-x

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  • DOI: https://doi.org/10.1007/s00380-020-01597-x

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