Are dapagliflozin (SGLT2 inhibitor) and steglatro (ertugliflozin) equally effective for treating heart failure?

Dapagliflozin and Steglatro (Ertugliflozin) Are NOT Equally Effective for Heart Failure

Dapagliflozin has robust, high-quality evidence demonstrating significant reductions in heart failure hospitalizations and cardiovascular death, while steglatro (ertugliflozin) has no proven efficacy for heart failure outcomes and should not be used for this indication. 1, 2, 3

Evidence Supporting Dapagliflozin

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Dapagliflozin reduced the composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85) in the DAPA-HF trial, which enrolled 4,744 patients with NYHA class II-IV heart failure and ejection fraction ≤40%. 1, 2, 3
• First worsening heart failure events were reduced by 30% (HR 0.70,95% CI 0.59-0.83), and cardiovascular death was reduced by 18% (HR 0.82,95% CI 0.69-0.98). 1, 4
• These benefits occurred regardless of diabetes status—45% of DAPA-HF participants had type 2 diabetes, and the effect was consistent in both diabetic and non-diabetic patients. 1, 2

Heart Failure with Mildly Reduced or Preserved Ejection Fraction (HFmrEF/HFpEF)

• The DELIVER trial demonstrated that dapagliflozin reduced the composite of worsening heart failure or cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) in 6,263 patients with ejection fraction >40%. 2, 3, 5
• Benefits were consistent across the entire ejection fraction spectrum, including patients with ejection fraction ≥60%. 5

Guideline Recommendations for Dapagliflozin

• The American Diabetes Association and American College of Cardiology strongly recommend dapagliflozin (Class I recommendation) for all patients with symptomatic heart failure regardless of ejection fraction or diabetes status. 1, 2, 3
• Dapagliflozin is FDA-approved specifically for reducing cardiovascular death and heart failure hospitalizations in adults with heart failure. 2, 4

Complete Absence of Evidence for Ertugliflozin (Steglatro)

No Heart Failure Outcome Trials

• Ertugliflozin has not been studied in any dedicated heart failure outcome trials comparable to DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, or DELIVER. 1
• The available evidence for SGLT2 inhibitors in heart failure comes exclusively from trials of empagliflozin, canagliflozin, dapagliflozin, and sotagliflozin—ertugliflozin is conspicuously absent from all major cardiovascular outcome trials. 1

Limited Cardiovascular Data

• While other SGLT2 inhibitors demonstrated 27-39% reductions in heart failure hospitalizations across multiple trials (EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58, CREDENCE), ertugliflozin has no comparable data. 1
• The guidelines explicitly state that SGLT2 inhibitors "with proven benefit in this patient population" should be used—ertugliflozin does not meet this criterion. 1

Clinical Algorithm for SGLT2 Inhibitor Selection in Heart Failure

For HFrEF (LVEF ≤40%)

1. Choose dapagliflozin 10 mg daily or empagliflozin 10 mg daily—both have Class I, high-quality evidence. 1, 2, 3
2. Do NOT use ertugliflozin—it lacks heart failure efficacy data. 1
3. Initiate regardless of diabetes status, background GDMT (ACE inhibitors, ARBs, beta-blockers, MRAs), or baseline natriuretic peptide levels. 2, 3

For HFmrEF/HFpEF (LVEF >40%)

1. Choose dapagliflozin 10 mg daily (DELIVER trial) or empagliflozin 10 mg daily (EMPEROR-Preserved trial). 2, 3, 5
2. Do NOT use ertugliflozin—no evidence exists for this population. 1

Contraindications to Consider

• eGFR <20-25 mL/min/1.73 m² (dapagliflozin can be used down to eGFR 25 mL/min/1.73 m²). 2, 3
• History of serious hypersensitivity to the specific SGLT2 inhibitor. 2
• Active diabetic ketoacidosis (though risk is minimal in non-diabetic patients). 2

Important Clinical Pitfalls

The "Class Effect" Misconception

• While empagliflozin, canagliflozin, and dapagliflozin show consistent heart failure benefits suggesting a class effect, this does NOT automatically extend to ertugliflozin without dedicated outcome trials. 1
• Guidelines emphasize using SGLT2 inhibitors "with proven benefit"—this language specifically excludes agents without trial data. 1

Timing of Initiation

• Dapagliflozin should be initiated during heart failure hospitalization in stabilized patients, as deferring initiation results in many eligible patients never receiving the medication within 1 year. 3
• Benefits occur within weeks of initiation and are maintained long-term. 2

Safety Monitoring

• Hypotension occurs in approximately 5.7% of patients, particularly those with volume depletion—assess volume status before initiation. 2
• Genital mycotic infections (1.5-1.7%) and urinary tract infections (2.3-2.7%) are manageable but should be monitored. 2
• A mild, transient decrease in eGFR may occur but does not indicate kidney injury and should not prompt discontinuation. 2, 3

Renal Protection Bonus

• Dapagliflozin provides additional renal protection beyond heart failure benefits, reducing the composite renal outcome by 44% (HR 0.56,95% CI 0.45-0.68) in the DAPA-CKD trial. 2, 3
• This renoprotective effect is independent of diabetes status and represents an additional advantage over ertugliflozin. 2