What is the preferred SGLT2 (sodium-glucose cotransporter 2) inhibitor, empagliflozin (Jardiance) or dapagliflozin (Farxiga), for patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD)?

Empagliflozin vs Dapagliflozin for Type 2 Diabetes with Established Cardiovascular Disease

Both empagliflozin and dapagliflozin are equally effective SGLT2 inhibitors for reducing cardiovascular outcomes in patients with type 2 diabetes and established cardiovascular disease, with no clinically meaningful differences between them. 1, 2

Evidence for Equivalent Cardiovascular Efficacy

The most recent and highest quality evidence demonstrates no significant difference in cardiovascular outcomes between these agents:

• A 2024 Danish nationwide target trial emulation of 57,276 patients found identical 6-year cardiovascular risk (10.0% vs 10.0%) between empagliflozin and dapagliflozin initiators, with a risk ratio of 1.00 (95% CI: 0.91-1.11). 1

• This equivalence held true across all relevant subgroups: patients with established atherosclerotic cardiovascular disease (risk ratio 0.92,95% CI: 0.74-1.14) and those with heart failure (risk ratio 1.04,95% CI: 0.79-1.37). 1

• A 2025 meta-analysis of 428,940 participants confirmed no significant differences in all-cause death (RR: 0.91,95% CI: 0.68-1.20), cardiovascular death (RR: 1.12,95% CI: 0.81-1.55), major adverse cardiovascular events (RR: 1.03,95% CI: 0.86-1.23), myocardial infarction, stroke, or heart failure-related events. 2

Guideline Recommendations Support Either Agent

Current guidelines from the American Diabetes Association and American College of Cardiology recommend SGLT2 inhibitors as a class for patients with type 2 diabetes and established cardiovascular disease, without preferential recommendation for one agent over another:

• In patients with type 2 diabetes and established ASCVD, multiple ASCVD risk factors, or CKD, an SGLT2 inhibitor with demonstrated cardiovascular benefit is recommended to reduce the risk of major adverse cardiovascular events and/or heart failure hospitalization. 3

• Both empagliflozin and dapagliflozin have FDA approval for cardiovascular risk reduction, though with slightly different labeled indications. 3, 4

Individual Trial Results Show Similar Magnitude of Benefit

While direct comparison shows equivalence, examining individual placebo-controlled trials reveals comparable effect sizes:

• Empagliflozin reduced cardiovascular death by 38% and heart failure hospitalization by 35% in EMPA-REG OUTCOME. 3, 5

• Dapagliflozin reduced heart failure hospitalization by 27% in DECLARE-TIMI 58 and showed a 26% reduction in the composite of worsening heart failure or cardiovascular death in DAPA-HF. 3, 5

• Meta-analyses confirm that both agents reduce atherosclerotic major adverse cardiovascular events to a comparable degree. 3

Practical Decision-Making Algorithm

Since cardiovascular efficacy is equivalent, base your choice on these factors:

1. Cost and insurance coverage - Select whichever agent has better formulary coverage or lower out-of-pocket cost for the patient, as median monthly costs are similar ($621 for dapagliflozin 10mg vs $627 for empagliflozin 25mg). 5

2. Renal function thresholds - Both agents should not be initiated if eGFR <45 mL/min/1.73 m². 3, 4

3. Heart failure with preserved ejection fraction - If this specific phenotype is present, dapagliflozin has additional evidence from the DELIVER trial showing 18% reduction in heart failure outcomes in patients with EF >40%. 5

4. Patient already on one agent - If cardiovascular outcomes are stable, there is no evidence to support switching between agents. 1

Important Safety Considerations

Both agents share identical safety profiles and precautions:

• Monitor for genital mycotic infections (most common adverse effect at >5% incidence) and urinary tract infections. 3, 6, 4

• Assess for euglycemic diabetic ketoacidosis risk, particularly before surgery or during acute illness. 3, 4

• Evaluate volume status before initiation, especially in elderly patients or those on diuretics, to prevent hypotension. 3, 4

• Consider reducing insulin or sulfonylurea doses by approximately 20% when initiating to prevent hypoglycemia. 3

Common Pitfall to Avoid

Do not assume that higher cardiovascular death reduction in EMPA-REG OUTCOME (38%) versus DECLARE-TIMI 58 (18% non-significant) means empagliflozin is superior. These trials had different patient populations (100% vs 41% with established ASCVD) and cannot be directly compared. 3, 1 The only valid comparison comes from head-to-head studies showing equivalence. 1, 2