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Impact of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) on Cardiovascular Outcomes in Heart Failure With Reduced

Fahd Mohammed Abdullah Makhsham1,2, Khaled Abdulbaqi Baggash Nasr1,2, Amer Abdulelah Saif Al-Sewaiee1,2

  • 1Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Cardiology Department, Nanfang Hospital, Southern Medical University, Guangzhou, CHN.

Cureus
|January 13, 2026
PubMed

Insights

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) significantly reduce cardiovascular mortality and heart failure hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF). Further research is needed to assess their impact on all-cause mortality.

Area of Science:

  • Cardiology
  • Pharmacology
  • Internal Medicine

Background:

  • Heart failure with reduced ejection fraction (HFrEF) remains a significant cause of cardiovascular morbidity and mortality.
  • Current treatment guidelines recommend a multi-drug approach to manage HFrEF.
  • Novel therapeutic agents are continuously being investigated to improve patient outcomes.

Purpose of the Study:

  • To systematically review and meta-analyze the efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in reducing cardiovascular events in patients with HFrEF.
  • To evaluate the impact of SGLT2i on hospitalization for heart failure, cardiovascular mortality, and all-cause mortality.
  • To assess the consistency of SGLT2i benefits across diabetic and non-diabetic patient subgroups.

Main Methods:

  • Systematic literature review and meta-analysis of randomized controlled trials (RCTs).
  • Inclusion of 12 publications, including subgroup analyses, comparing SGLT2i (empagliflozin, dapagliflozin, canagliflozin) with standard care in HFrEF patients.
  • Pooled data analysis to determine the risk reduction for key cardiovascular outcomes.

Main Results:

  • SGLT2i significantly reduced the risk of cardiovascular mortality by 23% (relative risk reduction).
  • SGLT2i significantly reduced the risk of hospitalization for heart failure by 25% (relative risk reduction).
  • No statistically significant reduction in all-cause mortality was observed with SGLT2i treatment.

Conclusions:

  • SGLT2i demonstrate significant cardioprotective effects in patients with HFrEF, reducing cardiovascular mortality and heart failure hospitalizations.
  • The benefits of SGLT2i extend to both diabetic and non-diabetic individuals with HFrEF.
  • While SGLT2i are valuable additions to HFrEF management, further longitudinal studies are warranted to investigate their effect on all-cause mortality.

Keywords:
cardiovascular mortalitydapagliflozinheart failuresglt2 inhibitorstype 2 diabetes

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