What is the difference between empagliflozin (SGLT2 inhibitor) and dapagliflozin (SGLT2 inhibitor)?

Empagliflozin and Dapagliflozin: Key Differences

Both empagliflozin and dapagliflozin are highly selective SGLT2 inhibitors with essentially equivalent cardiovascular and renal benefits, but they differ in their approved eGFR thresholds for initiation and continuation, 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, 2

Mechanism of Action and Selectivity

Both drugs work through the same fundamental mechanism:

• Empagliflozin and dapagliflozin are among the most selective SGLT2 inhibitors, distinguishing them from canagliflozin (which has greater SGLT1 inhibition) and sotagliflozin (a dual SGLT1/SGLT2 inhibitor) 1, 3
• Both inhibit SGLT2 in the proximal renal tubules (S1 and S2 segments), blocking glucose reabsorption and increasing urinary glucose excretion 4, 5
• Dapagliflozin additionally reduces sodium reabsorption and increases sodium delivery to the distal tubule, which may influence cardiac preload/afterload, sympathetic activity, and intraglomerular pressure through tubuloglomerular feedback 5

Critical Renal Function Thresholds

The most clinically significant difference lies in their approved eGFR cutoffs:

Dapagliflozin

• Can be initiated at eGFR ≥25 mL/min/1.73 m² for heart failure or chronic kidney disease indications 2
• May be continued even if eGFR falls below 25 mL/min/1.73 m² in patients already on therapy, until dialysis initiation 2, 5
• Not recommended for glycemic control when eGFR <45 mL/min/1.73 m² 2

Empagliflozin

• Approved for use at eGFR ≥30 mL/min/1.73 m² 1
• Has a higher minimum threshold than dapagliflozin for both initiation and continuation 1

Cardiovascular and Renal Outcomes

Real-world evidence shows no significant difference in cardiovascular outcomes between the two drugs:

• A propensity-matched study of 1,074 patients found no difference in MACE (3.7% vs. 4.8%, HR 1.31,95% CI 0.73-2.35, p=0.349) over 3 years 6
• No differences in all-cause death, myocardial infarction, stroke, or hospitalization for heart failure 6
• Network meta-analysis revealed dapagliflozin demonstrated superior efficacy in preventing atrial fibrillation compared to empagliflozin, though no differences existed for MACE, cardiovascular mortality, or heart failure hospitalization 7
• Both drugs maintain effectiveness in vulnerable populations including those with congestion, recent heart failure hospitalization, and elderly patients 1

Practical Clinical Differences

Dosing and Administration

• Both require no dose adjustment or up-titration 1
• Neither affects blood pressure, heart rate, or potassium levels significantly 1
• Both can be administered with or without food 4, 5

Glucose Excretion

• Dapagliflozin at 10 mg daily results in approximately 70 grams of glucose excretion per day 5, 8
• Empagliflozin at 10 mg daily results in approximately 64 grams per day, and 78 grams at 25 mg daily 4

Safety Profile Differences

• Pharmacovigilance data from 14,594 cases showed empagliflozin was more frequently reported (60.1% vs. dapagliflozin) 9
• Both drugs carry similar risks of ketoacidosis and Fournier's gangrene in diabetic patients 9
• Both have low risk of hypoglycemia, lower limb amputations, bone fracture, and diabetic ketoacidosis 1

Facilitating Other Therapies

Empagliflozin specifically demonstrated facilitation of MRA use:

• Patients on empagliflozin taking MRAs are less likely to discontinue MRAs or experience severe hyperkalemia 1
• Empagliflozin was associated with lower requirement for diuretic intensification even in patients with overt congestion 1

Clinical Decision Algorithm

Choose dapagliflozin when:

• eGFR is 20-29 mL/min/1.73 m² (empagliflozin not approved in this range) 1, 2
• Patient has history of or high risk for atrial fibrillation 7
• Chronic kidney disease with albuminuria (UACR 200-5000 mg/g) is present 2

Choose empagliflozin when:

• eGFR is ≥30 mL/min/1.73 m² 1
• Patient requires facilitation of MRA therapy or has concerns about hyperkalemia 1
• Patient has significant congestion requiring diuretic optimization 1

Either drug is appropriate when:

• eGFR is ≥30 mL/min/1.73 m² 1, 2
• Primary goal is cardiovascular risk reduction in heart failure or diabetes 6, 7
• Cost or formulary considerations favor one over the other 6

Common Pitfalls to Avoid

• Do not discontinue either drug solely because glucose-lowering efficacy has declined with falling eGFR - cardiovascular and renal benefits persist independently of glycemic effects 1, 3
• Withhold both drugs at least 3 days before major surgery or prolonged fasting to prevent postoperative ketoacidosis 2
• Hold both drugs during acute illness with reduced oral intake, fever, vomiting, or diarrhea 2
• Do not confuse the initial reversible eGFR dip (3-5 mL/min/1.73 m²) as a reason to discontinue - this is expected and associated with better long-term renal outcomes 2