Are Empagliflozin and Dapagliflozin the Same?
No, empagliflozin and dapagliflozin are not the same drug—they are two distinct SGLT2 inhibitors with nearly identical cardiovascular and renal benefits but differ in their approved eGFR thresholds for initiation, with dapagliflozin allowing use down to eGFR ≥20 mL/min/1.73 m² versus empagliflozin's threshold of ≥30 mL/min/1.73 m². 1
Class Similarities
Both drugs belong to the SGLT2 inhibitor class and share the same fundamental mechanism of action:
- Mechanism: Both block renal glucose reabsorption in the proximal tubule, increasing urinary glucose excretion independent of pancreatic β-cell function or insulin sensitivity 2, 3
- Selectivity: Empagliflozin and dapagliflozin are among the most selective SGLT2 inhibitors, distinguishing them from other agents in this class 1
- Cardiovascular outcomes: Both provide approximately 25% reduction in the composite endpoint of cardiovascular death or heart failure hospitalization (hazard ratio ~0.74-0.75) 1
- Heart failure benefits: Both reduce hospitalization for heart failure by approximately 30-35% across major trials (EMPA-REG OUTCOME showed HR 0.65, DECLARE-TIMI 58 showed HR 0.73) 4
- Renal protection: Both demonstrate renal composite endpoint reductions of approximately 40-50% (EMPA-REG: HR 0.54, DECLARE-TIMI 58: HR 0.53) 4
- Safety profile: Both have excellent and nearly identical safety profiles, with genital mycotic infections and urinary tract infections being the most common adverse events 1
- Dosing simplicity: Neither requires dose adjustment or up-titration, and neither significantly affects blood pressure, heart rate, or potassium levels 1
Critical Differences
Renal Function Thresholds (Most Important Clinical Distinction)
- Dapagliflozin: Can be initiated at eGFR ≥25 mL/min/1.73 m² for heart failure or chronic kidney disease indications, with use allowed down to eGFR ≥20 mL/min/1.73 m² 1
- Empagliflozin: Approved for use at eGFR ≥30 mL/min/1.73 m² 1
- Clinical implication: Choose dapagliflozin when eGFR is 20-29 mL/min/1.73 m², as empagliflozin is not approved in this range 1
Trial Population Differences
- EMPA-REG OUTCOME (empagliflozin): Enrolled 7,020 patients with 99% having established cardiovascular disease at baseline 4
- DECLARE-TIMI 58 (dapagliflozin): Enrolled 17,160 patients with only 41% having established cardiovascular disease, representing a broader, lower-risk population 4
- DAPA-HF (dapagliflozin): Excluded patients with eGFR <30 mL/min/1.73 m², while EMPEROR-Reduced (empagliflozin) included patients down to eGFR 20 mL/min/1.73 m² 1
Minor Safety Differences
One head-to-head trial showed slightly lower rates of urinary and genital infections with empagliflozin (2.34% & 3.1%) compared to dapagliflozin (7.08% & 8.66%), though both remain well-tolerated 5
Clinical Decision Algorithm
When choosing between empagliflozin and dapagliflozin:
Check eGFR first:
Both drugs are equivalent for:
Do not discontinue either drug solely because glucose-lowering efficacy has declined with falling eGFR, as cardiovascular and renal benefits persist independently of glycemic effects 1
Withhold both drugs at least 3 days before major surgery or prolonged fasting to prevent postoperative ketoacidosis 1
Common Pitfalls to Avoid
- Do not assume these drugs are interchangeable in advanced CKD—dapagliflozin has a lower eGFR threshold 1
- Do not stop either drug when eGFR declines below the glycemic efficacy threshold, as cardiorenal benefits continue 1
- Do not forget to reduce insulin dose by 10-20% or consider stopping sulfonylureas when initiating either drug to prevent hypoglycemia 6
- Do not continue either drug through major surgery without a 3-day washout period 1