What is the role of Dapagliflozin (SGLT2 inhibitor) in managing type 2 diabetes and heart failure?

Role of Dapagliflozin in Managing Type 2 Diabetes and Heart Failure

Dapagliflozin should be strongly recommended for patients with type 2 diabetes and heart failure (both HFrEF and HFpEF) to reduce the risk of worsening heart failure, cardiovascular death, and hospitalization for heart failure, regardless of baseline glycemic status. 1

Cardiovascular Benefits in Heart Failure

Dapagliflozin provides significant cardiovascular benefits in heart failure patients:

• Heart Failure with Reduced Ejection Fraction (HFrEF): In the DAPA-HF trial, dapagliflozin reduced:

  • Primary composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74 [95% CI 0.65-0.85]) 1, 2
  • First worsening heart failure event by 30% (HR 0.70 [95% CI 0.59-0.83]) 1
  • Cardiovascular death by 18% (HR 0.82 [95% CI 0.69-0.98]) 1, 2

• Heart Failure with Preserved Ejection Fraction (HFpEF): In the DELIVER trial, dapagliflozin reduced:

  • Primary composite outcome by 18% (HR 0.82 [95% CI 0.73-0.92]) in patients with heart failure and ejection fraction >40% 1, 3

• Consistent benefits regardless of diabetes status: The cardiovascular benefits were observed in patients with and without type 2 diabetes 1, 2, 3

• Mortality benefit: A meta-analysis showed dapagliflozin reduced all-cause mortality (RR = 0.89,95% CI: 0.82-0.97) 4

Glycemic Control in Type 2 Diabetes

Dapagliflozin effectively manages glycemia in type 2 diabetes:

• Lowers HbA1c by 0.6-0.8% with minimal risk of hypoglycemia when used as monotherapy 5
• Effective across a wide range of patients, including those on high-dose insulin therapy 6
• Can be used regardless of diabetes duration or β-cell function 5

FDA-Approved Indications

Dapagliflozin is FDA-approved for multiple indications 7:

1. Reducing risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease
2. Reducing risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure
3. Reducing risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple risk factors
4. Improving glycemic control in type 2 diabetes (adults and children ≥10 years)

Patient Selection and Monitoring

Ideal Candidates:

• Patients with type 2 diabetes and established HFrEF or HFpEF 1
• Patients with heart failure without diabetes (benefits extend beyond glycemic control) 1, 2
• Patients with type 2 diabetes at high risk for heart failure 7

Contraindications/Cautions:

• Type 1 diabetes (not recommended) 7
• eGFR <45 mL/min/1.73m² for glycemic control (ineffective) 7
• Polycystic kidney disease or recent immunosuppressive therapy for kidney disease 7
• History of serious hypersensitivity to dapagliflozin 7

Monitoring Requirements:

• Watch for symptoms of ketoacidosis (nausea, vomiting, abdominal pain, fatigue, trouble breathing) 7
• Monitor for dehydration, especially in elderly patients or those on diuretics 7
• Be alert for genital mycotic infections and urinary tract infections 7

Potential Side Effects

Common adverse effects include:

• Genital mycotic infections (7.4-14.3% vs. 3.0% with placebo) 6
• Urinary tract infections (8.4-13.8% vs. 5.6% with placebo) 6
• Volume depletion/dehydration 7
• Risk of euglycemic diabetic ketoacidosis 7

Clinical Pearls

1. Beyond glycemic control: Benefits of dapagliflozin in heart failure appear independent of glucose-lowering effects, as evidenced by similar outcomes in patients with and without diabetes 1

2. Prevention of diabetes: Dapagliflozin reduced the incidence of new-onset type 2 diabetes by 32% in non-diabetic heart failure patients 8

3. Dosing considerations: When adding dapagliflozin to insulin therapy, consider reducing insulin dose by approximately 20% to prevent hypoglycemia 5

4. Early benefits: Most adverse events like genital infections occur in the first 24 weeks of treatment and are typically single episodes that respond to routine management 6

5. Class effect: The cardiovascular benefits seen with dapagliflozin likely represent a class effect of SGLT2 inhibitors, with similar benefits observed with empagliflozin in the EMPEROR-Reduced trial 1

In conclusion, dapagliflozin represents a cornerstone therapy for patients with type 2 diabetes and heart failure, offering significant reductions in cardiovascular mortality and heart failure hospitalizations while providing effective glycemic control with an acceptable safety profile.