Which Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitor has better outcomes in patients with heart failure?

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Last updated: March 9, 2025View editorial policy

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From the Guidelines

Empagliflozin has demonstrated the most robust heart failure outcomes among SGLT2 inhibitors, with a significant 21% reduction in the primary composite endpoint of time to HF hospitalization or cardiovascular death, as shown in the EMPEROR-Preserved trial 1. The benefits of SGLT2 inhibitors in patients with heart failure are well-established, with reduced incidence of heart failure hospitalization and cardiovascular death observed in several clinical trials 1. Key points to consider when using SGLT2 inhibitors for heart failure management include:

  • Typical dosing is empagliflozin 10 mg daily or dapagliflozin 10 mg daily
  • Mechanisms of action include improved cardiac energetics, reduced cardiac preload and afterload, decreased inflammation, and inhibition of the sodium-hydrogen exchanger
  • Potential side effects include genital mycotic infections, urinary tract infections, and volume depletion
  • Patients with type 1 diabetes should not use these medications due to risk of diabetic ketoacidosis
  • SGLT2 inhibitors should be used as part of a comprehensive treatment approach that may include ACE inhibitors/ARBs, beta-blockers, and mineralocorticoid receptor antagonists as appropriate The most recent and highest quality study, EMPEROR-Preserved, suggests that empagliflozin is effective in reducing hospitalization for heart failure and cardiovascular death in patients with heart failure with preserved ejection fraction (HFpEF) 1. Additional benefits of empagliflozin include a significant reduction in total HF hospitalizations, decrease in the slope of the eGFR decline, and a modest improvement in QOL at 52 weeks 1. Overall, the evidence supports the use of empagliflozin as a first-line treatment for patients with heart failure, regardless of the presence or absence of diabetes.

From the FDA Drug Label

To reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. To reduce the risk of sustained eGFR decline, end stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression To reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure.

The FDA drug label does not answer the question of which SGLT2 inhibitor has better outcomes in patients with heart failure, as it does not provide a direct comparison between dapagliflozin 2 and empagliflozin 3. Both drugs are indicated to reduce the risk of hospitalization for heart failure and cardiovascular death in adults with heart failure, but the labels do not provide information on their relative efficacy.

From the Research

SGLT2 Inhibitors for Heart Failure

  • SGLT2 inhibitors, such as empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin, have been shown to reduce the risk of heart failure hospitalization and cardiovascular death in patients with heart failure 4, 5, 6.
  • Empagliflozin and dapagliflozin have been specifically studied in patients with heart failure with reduced ejection fraction (HFrEF) and have been shown to improve outcomes 7, 6, 8.

Comparative Outcomes of Empagliflozin and Dapagliflozin

  • A multicenter retrospective cohort study found that patients who initiated empagliflozin were less likely to experience the composite of all-cause mortality or hospitalization compared with patients who started dapagliflozin 7.
  • The study found that empagliflozin was associated with a lower risk of hospitalization (HR, 0.90 [95% CI, 0.86-0.94]) and a trend towards lower all-cause mortality (HR, 0.91 [95% CI, 0.82-1.00]) compared with dapagliflozin 7.

Clinical Benefits of Empagliflozin

  • A multinational randomized trial found that empagliflozin initiated in patients hospitalized for acute heart failure resulted in significant clinical benefit, including reduced risk of death from any cause, heart failure events, and improved symptoms 8.
  • The trial found that empagliflozin was well tolerated, with serious adverse events reported in 32.3% of patients treated with empagliflozin compared with 43.6% of patients treated with placebo 8.

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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