SGLT2 Inhibitor Use in Patients with Type 2 Diabetes Mellitus and Heart Failure

Main Article Content

Sarah Fraser
Elizabeth Swiggum

Keywords

SGLT2 inhibitor, HFrEF, HFpEF, Congestive Heart Failure, Type 2 Diabetes Mellitus

Abstract

Abstract
Type 2 diabetes mellitus and heart failure, both reduced and preserved ejection fraction phenotypes, are indi-vidually associated with significant morbidity and mortality and, when co-morbid, compound their risks for poor outcomes. Sodiumglucose co-transporter 2 inhibitors have demonstrated significant risk reduction in important clinical outcomes in both conditions and should be utilized as foundational therapy to simultaneously target these two diseases. This article will explore the evidence for managing heart failure and type 2 diabetes patients and identify opportunities to improve outcomes.



Résumé
Le diabète de type 2 et l’insuffisance cardiaque, qu’il s’agisse d’un phénotype de fraction d’éjection réduite ou préservée, sont associés individuellement à une morbidité et à une mortalité importantes et, en présence d’affections comorbides, exacerbent les risques de mauvais résultats. Les inhibiteurs du cotransporteur sodium-glucose de type 2 montrent une diminution importante des risques relatifs aux résultats cliniques importants dans les deux affections et devraient être utilisés comme traitement de base pour cibler les deux maladies à la fois. Cet article explore les données probantes sur la prise en charge des patients atteints d’insuffisance cardiaque et de diabète de type 2 et cerne des possibilités d’amélioration des résultats.

Abstract 42 | PDF Downloads 44 XML Downloads 14 HTML Downloads 17

References

1. Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393(10166):31-39. doi:10.1016/S0140-6736(18)32590-X.
2. Taylor SI, Blau JE, Rother KI, Beitelshees AL. SGLT2 inhibitors as adjunctive therapy for type 1 diabetes: balancing benefits and risks. Lancet Diabetes Endocrinol. 2019;7(12):949-958. doi:10.1016/S2213-8587(19)30154-8.
3. Yeung DF, Boom NK, Guo H, Lee DS, Schultz SE, Tu J v. Trends in the incidence and outcomes of heart failure in Ontario, Canada: 1997 to 2007. Can Med Assoc J. 2012;184(14):E765. doi:10.1503/CMAJ.111958/-/DC1.
4. McDonald M, Virani S, Chan M, et al. CCS/CHFS Heart Failure Guidelines Update: Defining a new pharmacologic standard of care for heart failure with reduced ejection fraction. Can J Cardiol. 2021;37(4):531-546. doi:10.1016/J.CJCA.2021.01.017.
5. van Deursen VM, Urso R, Laroche C, et al. Comorbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey. Eur J Heart Fail. 2014;16(1):103-111. doi:10.1002/EJHF.30.
6. Shimabukuro M, Higa N, Oshiro Y, Asahi T, Takasu N. Diagnostic utility of brain-natriuretic peptide for left ventricular diastolic dysfunction in asymptomatic type 2 diabetic patients. Diabetes Obes Metab. 2007;9(3):323-329. doi:10.1111/J.1463-1326.2006.00607.X.
7. Rashid M, Kwok CS, Gale CP, et al. Impact of co-morbid burden on mortality in patients with coronary heart disease, heart failure, and cerebrovascular accident: a systematic review and meta-analysis. Eur Heart J Qual Care Clin Outcomes. 2017;3(1):20-36. doi:10.1093/EHJQCCO/QCW025.
8. Mullens W, Damman K, Testani JM, et al. Evaluation of kidney function throughout the heart failure trajectory - a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2020;22(4):584-603. doi:10.1002/EJHF.1697.
9. Chu L, Fuller M, Jervis K, Ciaccia A, Abitbol A. Prevalence of chronic kidney disease in type 2 diabetes: The Canadian REgistry of Chronic Kidney Disease in Diabetes Outcomes (CREDO) Study. Clin Ther. 2021;43(9):1558-1573. doi:10.1016/J.CLINTHERA.2021.07.015.
10. Rosano GMC, Moura B, Metra M, et al. Patient profiling in heart failure for tailoring medical therapy. A consensus document of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2021;23(6):872-881. doi:10.1002/EJHF.2206.
11. Pinto LC, Rados DV, Remonti LR, Kramer CK, Leitao CB, Gross JL. Efficacy of SGLT2 inhibitors in glycemic control, weight loss and blood pressure reduction: a systematic review and meta-analysis. Diabetol Metab Syndr. 2015;7(S1):A58. doi:10.1186/1758-5996-7-S1-A58.
12. Liu XY, Zhang N, Chen R, Zhao JG, Yu P. Efficacy and safety of sodium–glucose co-transporter 2 inhibitors in type 2 diabetes: a meta-analysis of randomized controlled trials for 1 to 2 years. J Diabetes Complications. 2015;29(8):1295-1303. doi:10.1016/j.jdiacomp.2015.07.011.
13. Neuen BL, Young T, Heerspink HJL, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2019;7(11):845-854. doi:10.1016/S2213-8587(19)30256-6.
14. Heerspink HJL, Stefánsson B v., Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446. doi:10.1056/NEJMoa2024816.
15. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303.
16. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413-1424. doi:10.1056/NEJMoa2022190.
17. Bhatt DL, Verma S, Pitt B. EMPEROR-Preserved: A promise fulfilled. Cell Metab. 2021;33(11):2099-2103. doi:10.1016/j.cmet.2021.10.011.
18. World Health Organization. World Health Organization Model List of Essential Medicines: 22nd List.; 2021. 66 pages. Accessed June 18, 2022. WHO/MHP/HPS/EML/2021.02.
19. Verma S, Dhingra NK, Butler J, et al. Empagliflozin in the treatment of heart failure with reduced ejection fraction in addition to background therapies and therapeutic combinations (EMPEROR-Reduced): a post-hoc analysis of a randomised, double-blind trial. Lancet Diabetes Endocrinol. 2022;10(1):35-45. doi:10.1016/S2213-8587(21)00292-8.
20. Seidu S, Kunutsor SK, Topsever P, Khunti K. Benefits and harms of sodium-glucose co-transporter-2 inhibitors (SGLT2-I) and renin-angiotensin-aldosterone system inhibitors (RAAS-I) versus SGLT2-Is alone in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Endocrinol Diabetes Metab. 2022;5(1). doi:10.1002/EDM2.303.
21. Rossing P, Inzucchi SE, Vart P, et al. Dapagliflozin and new-onset type 2 diabetes in patients with chronic kidney disease or heart failure: pooled analysis of the DAPA-CKD and DAPA-HF trials. Lancet Diabetes Endocrinol. 2022;10(1):24-34. doi:10.1016/S2213-8587(21)00295-3.
22. Donnan JR, Grandy CA, Chibrikov E, et al. Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis. BMJ Open. 2019;9(1):e022577. doi:10.1136/bmjopen-2018-022577.
23. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451-1461. doi:10.1056/NEJMoa2107038.
24. Nassif ME, Windsor SL, Borlaug BA, et al. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial. Nat Med. 2021;27(11):1954-1960. doi:10.1038/s41591-021-01536-x.
25. Solomon SD, de Boer RA, DeMets D, et al. Dapagliflozin in heart failure with preserved and mildly reduced ejection fraction: rationale and design of the DELIVER trial. Eur J Heart Fail. 2021;23(7):1217-1225. doi:10.1002/EJHF.2249.
26. Bhatt DL, Szarek M, Steg PG, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021;384(2):117-128. doi:10.1056/NEJMoa2030183.
27. Damman K, Beusekamp JC, Boorsma EM, et al. Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF). Eur J Heart Fail. 2020;22(4):713-722. doi:10.1002/EJHF.1713.
28. Voors AA, Angermann CE, Teerlink JR, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022;28(3):568-574. doi:10.1038/s41591-021-01659-1.
29. Schulze PC, Bogoviku J, Westphal J, et al. Effects of Early Empagliflozin Initiation on Diuresis and Kidney Function in Patients With Acute Decompensated Heart Failure (EMPAG-HF). Circulation. 2022;146(4):289–298. doi:10.1161/CIRCULATIONAHA.122.059038
30. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295-2306. doi:10.1056/NEJMoa1811744.
31. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):1810-1852. doi:10.1161/CIR.0B013E31829E8807.
32. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128. doi:10.1056/NEJMoa1504720.
33. Yu X, Zhang S, Zhang L. Newer perspectives of mechanisms for euglycemic diabetic ketoacidosis. Int J Endocrinol. 2018;2018:1-8. doi:10.1155/2018/7074868.
34. Lipscombe L, Booth G, Butalia S, et al. Pharmacologic glycemic management of type 2 diabetes in adults. Can J Diabetes. 2018;42:S88-S103. doi:10.1016/j.jcjd.2017.10.034.
35. Lam D, Shaikh A. Real-Life Prescribing of SGLT2 inhibitors: how to handle the other medications, including glucose-lowering drugs and diuretics. Kidney360. 2021;2(4):742-746. doi:10.34067/KID.0000412021.
36. Woo VC, Berard LD, Bajaj HS, Ekoé JM, Senior PA. Considerations for initiating a sodium-glucose co-transporter 2 inhibitor in adults with type 2 diabetes using insulin. Can J Diabetes. 2018;42(1):88-93. doi:10.1016/J.JCJD.2017.01.009.
37. Liu J, Li L, Li S, et al. Effects of SGLT2 inhibitors on UTIs and genital infections in type 2 diabetes mellitus: a systematic review and meta-analysis. Sci Rep. 2017;7(1). doi:10.1038/S41598-017-02733-W.