What is the role of dapagliflozin (SGLT2 inhibitor) in managing heart failure in patients with type 2 diabetes?

Dapagliflozin for Heart Failure

Dapagliflozin 10 mg once daily is strongly recommended for all adults with heart failure (both reduced and preserved ejection fraction) to reduce cardiovascular death, hospitalization for heart failure, and urgent heart failure visits, regardless of whether they have type 2 diabetes. 1, 2

Evidence-Based Indications

For Heart Failure with Reduced Ejection Fraction (HFrEF, LVEF ≤40%):

• Dapagliflozin reduces the composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85) over 18 months in the DAPA-HF trial 1, 3
• First worsening heart failure events are reduced by 30% (HR 0.70,95% CI 0.59-0.83) 1
• Cardiovascular death is reduced by 18% (HR 0.82,95% CI 0.69-0.98) 1, 3
• All-cause mortality is reduced by 17% (HR 0.83,95% CI 0.71-0.97) 3

For Heart Failure with Preserved Ejection Fraction (HFpEF, LVEF >40%):

• Dapagliflozin reduces the composite of worsening heart failure or cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) in the DELIVER trial 1
• Benefits are consistent across the entire spectrum of ejection fraction above 40% 1

Clinical Algorithm for Implementation

Step 1: Identify Eligible Patients

• Any adult with symptomatic heart failure (NYHA class II-IV) regardless of ejection fraction 1, 2
• Elevated natriuretic peptides (NT-proBNP ≥300 pg/mL, or ≥600 pg/mL if atrial fibrillation) 4
• eGFR ≥30 mL/min/1.73 m² for HFrEF; no specific eGFR threshold for HFpEF 4, 3

Step 2: Exclude Contraindications

• Serious hypersensitivity to dapagliflozin 2
• Polycystic kidney disease 2
• Recent or current immunosuppressive therapy for kidney disease 2

Step 3: Initiate Treatment

• Start dapagliflozin 10 mg once daily 1, 2
• No dose titration required—full dose from initiation 5
• Can be initiated during hospitalization once patient is stabilized 5

Step 4: Monitor for Safety

• Volume depletion signs (dizziness, lightheadedness, orthostatic hypotension)—especially in patients on diuretics, age ≥65 years, or with baseline kidney impairment 2
• Genital mycotic infections (1.5-1.7% incidence) and urinary tract infections (2.3-2.7% incidence) 5
• Diabetic ketoacidosis risk is minimal in non-diabetic patients but monitor if patient becomes acutely ill, dehydrated, or undergoes surgery 2

Benefits Independent of Diabetes Status

The cardiovascular benefits of dapagliflozin are consistent regardless of diabetes status:

• In DAPA-HF, 45% had type 2 diabetes and benefits were identical in those with and without diabetes 1, 3
• In DELIVER, 44% had type 2 diabetes with consistent benefits across glycemic categories (normoglycemia, prediabetes, type 2 diabetes) 1, 6
• A meta-analysis of 21,947 patients confirmed benefits across the entire spectrum of glycemic status 1

Additional Quality of Life Benefits

Beyond mortality and morbidity reduction:

• Improves symptoms, physical limitations, and quality of life in heart failure patients 1
• Reduces systolic blood pressure and body weight without increasing hypoglycemia risk in non-diabetic patients 7
• Benefits appear within weeks of initiation and are maintained long-term 5

Critical Safety Considerations

Common Pitfall—Volume Depletion:

• Occurs in approximately 5.7% of patients 5
• Higher risk in patients taking loop diuretics, on low-sodium diets, age ≥65 years, or with baseline kidney dysfunction 2
• Counsel patients to maintain adequate hydration and report symptoms of dizziness or lightheadedness 2

Transient eGFR Decline:

• A mild, transient decrease in eGFR may occur after initiation but does not indicate kidney injury 5
• Do not discontinue dapagliflozin for mild eGFR changes—this is a hemodynamic effect, not nephrotoxicity 5

Ketoacidosis Risk:

• Extremely low risk in non-diabetic heart failure patients 5
• In diabetic patients, risk increases with acute illness, dehydration, surgery, or reduced insulin dosing 2
• Can occur even with blood glucose <250 mg/dL 2

Comparison with Other SGLT2 Inhibitors

Dapagliflozin and empagliflozin have the strongest evidence:

• Both have dedicated heart failure outcome trials (DAPA-HF, DELIVER for dapagliflozin; EMPEROR-Reduced, EMPEROR-Preserved for empagliflozin) 1
• Empagliflozin showed similar 21% reduction in cardiovascular death or heart failure hospitalization in EMPEROR-Reduced 1
• Ertugliflozin lacks dedicated heart failure outcome trials and should not be used for this indication 5

Class Effect Considerations

The benefits represent a class effect of SGLT2 inhibitors:

• Canagliflozin showed 33% reduction in heart failure hospitalization in CANVAS and 39% reduction in CREDENCE 1
• Sotagliflozin (dual SGLT1/SGLT2 inhibitor) showed similar benefits in SOLOIST-WHF and SCORED trials 1
• Benefits appear unrelated to glucose lowering, given comparable outcomes in patients with and without diabetes 1