What are the potential downsides of replacing empagliflozin (SGLT2 inhibitor) with dapagliflozin (SGLT2 inhibitor)?

Replacing Empagliflozin with Dapagliflozin: Clinical Considerations

There is minimal clinical downside to replacing empagliflozin with dapagliflozin, as both SGLT2 inhibitors demonstrate equivalent cardiovascular and renal benefits with similar safety profiles, though dapagliflozin offers the advantage of use at lower eGFR thresholds (≥20 mL/min/1.73 m² versus ≥30 mL/min/1.73 m²). 1

Cardiovascular and Heart Failure Outcomes

Both agents provide comparable benefits for heart failure with reduced ejection fraction (HFrEF):

• Meta-analysis of DAPA-HF and EMPEROR-Reduced trials demonstrated consistent effects on hospitalization for heart failure, all-cause death, cardiovascular death, and renal outcomes between empagliflozin and dapagliflozin 2
• Both drugs reduce the composite endpoint of cardiovascular death or heart failure hospitalization by approximately 25% (hazard ratio ~0.74-0.75) 2
• Neither agent requires dose adjustment or up-titration, and both maintain effectiveness in vulnerable populations including those with recent heart failure hospitalization 1

Renal Function Thresholds: The Key Practical Difference

The most clinically relevant difference is the approved eGFR threshold:

• Dapagliflozin can be initiated at eGFR ≥25 mL/min/1.73 m² for heart failure or chronic kidney disease indications, and is approved for use down to eGFR ≥20 mL/min/1.73 m² 1
• Empagliflozin requires eGFR ≥30 mL/min/1.73 m² 1
• The DAPA-HF trial excluded patients with eGFR <30 mL/min/1.73 m², while EMPEROR-Reduced included patients down to eGFR 20 mL/min/1.73 m² 2

Clinical Algorithm for Switching:

• If patient's eGFR is ≥30 mL/min/1.73 m²: Either agent is appropriate with no meaningful clinical difference 1
• If patient's eGFR is 20-29 mL/min/1.73 m²: Dapagliflozin is the only approved option 1

Glycemic Control Differences

While both agents are effective, some evidence suggests modest differences in glucose-lowering:

• One head-to-head trial showed empagliflozin produced greater HbA1c reduction (-1.7±0.9% versus -1.2±1.4%, p=0.002) and fasting blood sugar reduction (p=0.001) compared to dapagliflozin 3
• A separate 52-week observational study confirmed empagliflozin was more effective in reducing HbA1c when used as fourth-line oral therapy 4
• However, these glycemic differences are clinically minor and should not drive the decision, as cardiovascular and renal benefits persist independently of glucose-lowering effects 1

Safety Profile Comparison

Both agents have excellent and nearly identical safety profiles:

• Genital mycotic infections and urinary tract infections are the most common adverse events for both drugs 2, 5
• One study reported slightly lower rates of urinary infections (2.34% versus 7.08%, p=0.003) and genital infections (3.1% versus 8.66%, p=0.005) with empagliflozin compared to dapagliflozin 3
• Both have very low intrinsic risk of hypoglycemia when used as monotherapy 6
• Neither significantly affects blood pressure, heart rate, or potassium levels 1

Critical Safety Precautions (Apply to Both Agents)

When switching between these agents, maintain the same precautions:

• Withhold both drugs at least 3 days before major surgery or prolonged fasting to prevent postoperative euglycemic ketoacidosis 1
• If patient is on insulin, reduce insulin dose by 10-20% when initiating either SGLT2 inhibitor 6
• If patient is on sulfonylureas with HbA1c <8.5%, strongly consider stopping the sulfonylurea 6
• Do not discontinue either drug solely because glucose-lowering efficacy has declined with falling eGFR, as cardiovascular and renal benefits persist independently 1

Common Pitfalls to Avoid

• Do not assume empagliflozin must be discontinued when eGFR falls below 30 mL/min/1.73 m² - this is the appropriate time to switch to dapagliflozin rather than stopping SGLT2 inhibitor therapy entirely 1
• Do not expect meaningful differences in cardiovascular outcomes between the two agents, as they are equivalent in this regard 2, 1
• Avoid switching based solely on minor glycemic differences, as the cardiovascular and renal benefits are the primary therapeutic targets 1