International Journal of Clinical and Pharmaceutical Innovations

An International Peer Reviewed Open Access Journal

ISSN (Online): 3142-8665
CODEN (USA): IJCPSM
Monthly Publication

editor@ijcpi.com

International Journal of Clinical and Pharmaceutical Innovations

An International Peer Reviewed Open Access Journal

ISSN (Online): 3142-8665
CODEN (USA): IJCPSM
Monthly Publication

editor@ijcpi.com

CLINICAL OUTCOMES OF DAPAGLIFLOZIN IN HEART FAILURE WITH REDUCED EJECTION FRACTION: A COMPREHENSIVE REVIEW

Akula Amulya, Ayesha Fathima, Gariga Deekshitha, Sreemantula Divya*
Full Article DOI

Abstract

Heart failure with reduced ejection fraction (HFrEF) remains an important health challenge worldwide, especially in Asia and India where there is a younger patient population, along with a high prevalence of type 2 diabetes, hypertension, and chronic kidney disease. Despite advances in the standard management of heart failure, considerable residual risk of hospitalization and death exists. This review highlights the clinical significance of dapagliflozin and includes data from the DECLARE-TIMI 58 trial and its subgroup analyses with more than 17,000 patients having type 2 diabetes. Dapagliflozin (10 mg per day) decreased the rate of cardiovascular mortality or hospitalization due to HF by 17% and the rate of heart failure hospitalization by 27%. These effects were independent of sub-group analysis, including in patients with HFrEF, with no impact on the eGFR decline and adverse effects primarily limited to genital infections. Also, real-life data and economic analysis provide additional evidence to consider this drug. Nowadays, international and Indian guidelines recommend dapagliflozin as one of the mainstays of the therapy in patients with HFrEF along with other GDMT. In conclusion, dapagliflozin offers a safe, effective strategy to improve outcomes in HFrEF, particularly in resource limited settings. Early and wider adoption could significantly decrease the burden of heart failure.

References

  • Haller PM, Wiviott SD, Berg DD, Jarolim P, Goodrich EL, Bhatt DL, Gause-Nilsson I, Leiter LA, McGuire DK, Wilding JPH, Raz I, Sabatine MS, Morrow DA. Galectin-3 and kidney function in type 2 diabetes treated with dapagliflozin: Analysis from DECLARE-TIMI 58. ESC Heart Fail. 2025 Dec; 12(6): 3981-3986. doi: 10.1002/ehf2.15415. Epub 2025 Sep 15. 
  • Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev., 2024 May 21; 5(5): CD015588. doi: 10.1002/14651858.CD015588.pub2.
  • Schechter M, Wiviott SD, Raz I, Goodrich EL, Rozenberg A, Yanuv I, Murphy SA, Zelniker TA, Fredriksson M, Johansson PA, Leiter LA, Bhatt DL, McGuire DK, Wilding JPH, Gause-Nilsson IAM, Cahn A, Langkilde AM, Sabatine MS, Mosenzon O. Effects of dapagliflozin on hospitalisations in people with type 2 diabetes: post-hoc analyses of the DECLARE-TIMI 58 trial. Lancet Diabetes Endocrinol, 2023 Apr; 11(4): 233-241. doi: 10.1016/S2213-8587(23)00009-8. Epub 2023 Mar 3. 
  • Zelniker TA, Wiviott SD, Mosenzon O, Goodrich EL, Jarolim P, Cahn A, Bhatt DL, Leiter LA, McGuire DK, Wilding J, Averkov O, Budaj A, Parkhomenko A, Ray KK, Gause-Nilsson I, Langkilde AM, Fredriksson M, Raz I, Sabatine MS, Morrow DA. Association of Cardiac Biomarkers With Major Adverse Cardiovascular Events in High-risk Patients With Diabetes: A Secondary Analysis of the DECLARE-TIMI      58 Trial. JAMA Cardiol, 2023 May 1; 8(5): 503-509. doi:10.1001/jamacardio.2023.0019. 
  • Mosenzon O, Raz I, Wiviott SD, Schechter M, Goodrich EL, Yanuv I, Rozenberg A, Murphy SA, Zelniker TA, Langkilde AM, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Wilding JPH, McGuire DK, Bhatt DL, Leiter LA, Cahn A, Dwyer JP, Heerspink HJL, Sabatine MS. Dapagliflozin and Prevention of Kidney Disease Among Patients With Type 2 Diabetes: Post Hoc Analyses From the DECLARE-TIMI 58 Trial. Diabetes Care, 2022 Oct 1; 45(10): 2350-2359. doi: 10.2337/dc22-0382. 6. Oyama K, Raz I, Cahn A, Goodrich EL, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, GauseNilsson IAM, Mosenzon O, Sabatine MS, Wiviott SD. Efficacy and Safety of Dapagliflozin According to Background Use of Cardiovascular Medications in Patients With Type 2 Diabetes: A Prespecified Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol, 2022 Sep 1; 7(9): 914-923. doi: 10.1001/jamacardio.2022.2006. 
  • Furtado RHM, Raz I, Goodrich EL, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Aylward P, Dalby AJ, Dellborg M, Dimulescu D, Nicolau JC, Oude Ophuis AJM, Cahn A, Mosenzon O, Gause-Nilsson I, Langkilde AM, Sabatine MS, Wiviott SD. Efficacy and Safety of Dapagliflozin in Type 2 Diabetes According to Baseline Blood Pressure: Observations From DECLARE-TIMI 58 Trial. Circulation, 2022 May 24; 145(21):          1581-1591. doi: 10.1161/CIRCULATIONAHA.121.058103. Epub 2022 May 5. 
  • Cahn A, Wiviott SD, Mosenzon O, Goodrich EL, Murphy SA, Yanuv I, Rozenberg A, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Gause-Nilsson IAM, Langkilde AM, Sabatine MS, Raz I. Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58. Diabetes Care, 2022 Apr 1; 45(4):             938-946. doi: 10.2337/dc21-1744. 
  • Oyama K, Raz I, Cahn A, Kuder J, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Park KS, Goudev A, Diaz R, Spinar J, Gause-Nilsson IAM, Mosenzon O, Sabatine MS, Wiviott SD. Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE-TIMI 58 trial. Eur Heart J., 2022 Aug 14; 43(31): 2958-2967. doi: 10.1093/eurheartj/ehab530. 
  • Mosenzon O, Wiviott SD, Heerspink HJL, Dwyer JP, Cahn A, Goodrich EL, Rozenberg A, Schechter M, Yanuv I, Murphy SA, Zelniker TA, Gause-Nilsson IAM, Langkilde AM, Fredriksson M, Johansson PA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Sabatine MS, Raz I. The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58. Diabetes Care, 2021 Aug; 44(8): 1805-1815. doi: 10.2337/dc21-0076. Epub 2021 Jul 7. 
  • Cherney DZI, Dagogo-Jack S, McGuire DK, Cosentino F, Pratley R, Shih WJ, Frederich R, Maldonado M, Liu J, Wang S, Cannon CP; VERTIS CV Investigators. Kidney outcomes using a sustained >/=40% decline in eGFR: A meta-analysis of SGLT2 inhibitor trials. Clin Cardiol, 2021 Aug; 44(8): 1139-1143. doi: 10.1002/clc.23665. Epub 2021 Jun 15. 
  • Zelniker TA, Raz I, Mosenzon O, Dwyer JP, Heerspink HHJL, Cahn A, Goodrich EL, Im K, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Gause-Nilsson I, Langkilde AM, Sabatine MS, Wiviott SD. Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes: A Prespecified Secondary Analysis of a Randomized    Clinical Trial.  JAMA Cardiol, 2021 Jul 1; 6(7): 801-810. doi: 10.1001/jamacardio.2021.0660.
  • Cahn A, Raz I, Leiter LA, Mosenzon O, Murphy SA, Goodrich EL, Yanuv I, Rozenberg A, Bhatt DL, McGuire DK, Wilding JPH, Gause-Nilsson IAM, Langkilde AM, Sabatine MS, Wiviott SD. Cardiovascular, Renal, and Metabolic Outcomes of Dapagliflozin Versus Placebo in a Primary Cardiovascular Prevention Cohort: Analyses From DECLARE-TIMI 58. Diabetes Care, 2021 May; 44(5): 1159-1167. doi: 10.2337/dc20-2492. Epub 2021 Mar 2. 
  • O'Donoghue ML, Kato ET, Mosenzon O, Murphy SA, Cahn A, Herrera M, Tankova T, Smahelova A, Merlini P, Gause-Nilsson I, Langkilde AM, McGuire DK, Wilding JPH, Leiter LA, Bhatt DL, Raz I, Sabatine MS, Wiviott SD. The efficacy and safety of dapagliflozin in women and men with type 2 diabetes mellitus. Diabetologia, 2021 Jun; 64(6): 1226-1234. doi: 10.1007/s00125-021-05399-2. Epub 2021 Feb 20. 
  • Bonaca MP, Wiviott SD, Zelniker TA, Mosenzon O, Bhatt DL, Leiter LA, McGuire DK, Goodrich EL, De Mendonca Furtado RH, Wilding JPH, Cahn A, Gause-Nilsson IAM, Johanson P, Fredriksson M, Johansson PA, Langkilde AM, Raz I, Sabatine MS. Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58. 
  • Circulation, 2020 Aug 25; 142(8): 734-747. doi: 10.1161/CIRCULATIONAHA.119.044775. Epub 2020 Aug 3. 
  • Zelniker TA, Bonaca MP, Furtado RHM, Mosenzon O, Kuder JF, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Budaj A, Kiss RG, Padilla F, Gause-Nilsson I, Langkilde AM, Raz I, Sabatine MS, Wiviott SD. Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: Insights From the DECLARE-TIMI 58 Trial. Circulation, 2020 Apr 14; 141(15): 1227-1234. doi: 10.1161/CIRCULATIONAHA.119.044183. Epub 2020 Jan 27. 
  • Cahn A, Mosenzon O, Wiviott SD, Rozenberg A, Yanuv I, Goodrich EL, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Langkilde AM, Sabatine MS, Raz I. Efficacy and Safety of Dapagliflozin in the Elderly: Analysis From the DECLARE-TIMI 58 Study. Diabetes Care, 2020 Feb; 43(2): 468-475. doi: 10.2337/dc19-1476. Epub 2019 Dec 16. 
  • Berg DD, Wiviott SD, Scirica BM, Gurmu Y, Mosenzon O, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Johanson P, Johansson PA, Langkilde AM, Raz I, Braunwald E, Sabatine MS. Heart Failure Risk Stratification and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes Mellitus. Circulation, 2019 Nov 5; 140(19): 1569-1577. doi: 10.1161/CIRCULATIONAHA.119.042685. Epub 2019 Aug 31. 
  • Mosenzon O, Wiviott SD, Cahn A, Rozenberg A, Yanuv I, Goodrich EL, Murphy SA, Heerspink HJL, Zelniker TA, Dwyer JP, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Kato ET, Gause-Nilsson IAM, Fredriksson M, Johansson PA, Langkilde AM, Sabatine MS, Raz I. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE-TIMI 58 randomised trial. Lancet Diabetes Endocrinol, 2019 Aug; 7(8): 606-617. doi: 10.1016/S2213-8587(19)30180-9. Epub 2019 Jun 10. 
  • Furtado RHM, Bonaca MP, Raz I, Zelniker TA, Mosenzon O, Cahn A, Kuder J, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Ruff CT, Nicolau JC, Gause-Nilsson IAM, Fredriksson M, Langkilde AM, Sabatine MS, Wiviott SD. Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction. Circulation, 2019 May 28; 139(22): 2516-2527. doi: 10.1161/CIRCULATIONAHA.119.039996. Epub 2019 Mar 18. 
  • Kato ET, Silverman MG, Mosenzon O, Zelniker TA, Cahn A, Furtado RHM, Kuder J, Murphy SA, Bhatt DL, Leiter LA, McGuire DK, Wilding JPH, Bonaca MP, Ruff CT, Desai AS, Goto S, Johansson PA, Gause-Nilsson I, Johanson P, Langkilde AM, Raz I, Sabatine MS, Wiviott SD. Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus. Circulation, 2019 May 28; 139(22):        2528-2536. doi: 10.1161/CIRCULATIONAHA.119.040130. Epub 2019 Mar 18. 
  • Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder 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. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med., 2019 Jan 24; 380(4): 347-357. doi: 10.1056/NEJMoa1812389. Epub 2018 Nov 10. 
  • Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Bansilal S, Bhatt DL, Leiter LA, McGuire DK, Wilding JP, Gause-Nilsson IA, Langkilde AM, Johansson PA, Sabatine MS. The design and rationale for the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 Trial. Am Heart J., 2018 Jun; 200: 83-89. doi: 10.1016/j.ahj.2018.01.012. Epub 2018 Feb 7. 
  • Wittbrodt ET, Eudicone JM, Bell KF, Enhoffer DM, Latham K, Green JB. Eligibility varies among the 4 sodium-glucose cotransporter-2 inhibitor cardiovascular outcomes trials: implications for the general type 2 diabetes US population. Am J Manag Care, 2018 Apr; 24(8 Suppl): S138-S145. 
  • Bloch MJ. Blood pressure effects of SGLT2 inhibitors make them an attractive option in diabetic patients with hypertension. J Am Soc Hypertens, 2016 Mar; 10(3): 186-7. doi: 10.1016/j.jash.2016.01.001. No abstract available. 
  • Leiter LA, Cefalu WT, de Bruin TW, Xu J, Parikh S, Johnsson E, Gause-Nilsson I. Long-term maintenance of efficacy of dapagliflozin in patients with type 2 diabetes mellitus and cardiovascular disease. Diabetes Obese Metab., 2016 Aug; 18(8): 766-74. doi: 10.1111/dom.12666. Epub 2016 May 12. 

QR

QR Code

Citation

Akula Amulya1, Ayesha Fathima2, Gariga Deekshitha3, Sreemantula Divya4*. (2026). Clinical Outcomes Of Dapagliflozin In Heart Failure With Reduced Ejection Fraction: A Comprehensive Review. International Journal of Clinical and Pharmaceutical Innovations, 1(4), 41-51.
DOI: https://doi.org/10.5281/zenodo.21037493

Copyright © Creative Commons Attribution 4.0 (CC BY 4.0)

Keywords

Dapagliflozin, SGLT2 inhibitors, HFrEF, DECLARE-TIMI 58, heart failure, cardiorenal protection.