What is the difference between dapagliflozin and Jardiance (empagliflozin) for treating type 2 diabetes, particularly in patients with impaired renal function?

Dapagliflozin vs Empagliflozin (Jardiance): Head-to-Head Comparison

Both dapagliflozin and empagliflozin are highly effective SGLT2 inhibitors with proven cardiovascular and renal benefits, but empagliflozin has stronger mortality data in patients with established cardiovascular disease, while dapagliflozin has more robust evidence in chronic kidney disease and can be initiated at lower eGFR thresholds (≥25 mL/min/1.73 m² vs ≥30 mL/min/1.73 m²). 1, 2

Key Differences in Clinical Evidence

Cardiovascular Outcomes in Type 2 Diabetes with Established CVD

Empagliflozin demonstrates superior mortality benefit in patients with established atherosclerotic cardiovascular disease:

• In EMPA-REG OUTCOME, empagliflozin reduced 3-point MACE with HR 0.86 (p=0.04 for superiority) and showed significant cardiovascular death reduction of 38% 1
• Dapagliflozin in DECLARE-TIMI 58 did not achieve superiority for 3-point MACE (HR 0.93; 95% CI 0.84-1.03), though it reduced cardiovascular death or heart failure hospitalization (HR 0.83; 95% CI 0.73-0.95) 1, 3
• For patients with type 2 diabetes and established ASCVD prioritizing mortality reduction, empagliflozin has stronger evidence 1

Heart Failure Indications (With or Without Diabetes)

Both agents have Class I evidence for heart failure across the ejection fraction spectrum:

• Dapagliflozin (DAPA-HF): 26% reduction in worsening heart failure or cardiovascular death in HFrEF (HR 0.74; 95% CI 0.65-0.85) 1, 4
• Empagliflozin (EMPEROR-Reduced): 25% reduction in cardiovascular death or heart failure hospitalization in HFrEF (HR 0.75; 95% CI 0.65-0.86) 1, 4
• Both agents effective in HFpEF (DELIVER for dapagliflozin, EMPEROR-Preserved for empagliflozin) 1, 4
• For heart failure indications, choose either agent based on availability and cost—both have equivalent Class I recommendations 1, 4

Chronic Kidney Disease Protection

Dapagliflozin has more extensive CKD-specific evidence and can be initiated at lower eGFR:

• DAPA-CKD demonstrated 39% reduction in composite renal outcome (sustained eGFR decline ≥50%, ESKD, or renal/cardiovascular death) with HR 0.61 (95% CI 0.51-0.72) in patients with eGFR 25-75 mL/min/1.73 m² 2, 3
• Renal-specific composite reduced by 44% (HR 0.56; 95% CI 0.45-0.68) 2, 3
• Dapagliflozin can be initiated at eGFR ≥25 mL/min/1.73 m² for cardiovascular/renal protection, while empagliflozin data supports initiation at eGFR ≥30 mL/min/1.73 m² 2
• CREDENCE trial with canagliflozin showed similar renal benefits, but dapagliflozin has the most robust dedicated CKD trial data 1, 2

Dosing and Renal Function Considerations

Glycemic Control Thresholds

• Neither agent should be initiated for glycemic control if eGFR <45 mL/min/1.73 m² due to reduced glucose-lowering efficacy 2, 5
• At eGFR 30-45 mL/min/1.73 m², glucose-lowering efficacy is significantly impaired, but cardiovascular/renal benefits persist 2, 5

Cardiovascular/Renal Protection Thresholds

• Dapagliflozin: Initiate at eGFR ≥25 mL/min/1.73 m² at fixed 10 mg daily dose 2
• Empagliflozin: Initiate at eGFR ≥30 mL/min/1.73 m² based on trial inclusion criteria 1
• If eGFR falls below initiation threshold during treatment, both agents may be continued until dialysis 2

Expected eGFR Changes

• Both agents cause transient, reversible eGFR dip of 3-5 mL/min/1.73 m² within first 1-4 weeks 2, 6
• This hemodynamic effect is not kidney injury and should not prompt discontinuation 2, 6
• Check eGFR 1-2 weeks after initiation; if decrease >30% from baseline with hypovolemia signs, reduce diuretics first 2

Safety Profile Differences

Common to Both Agents

• Genital mycotic infections (6% vs 1% placebo), more common in women 2, 7
• Urinary tract infections (2.3-2.7%) 4
• Volume depletion risk, especially with concurrent diuretics or eGFR <60 mL/min/1.73 m² 1, 2
• Euglycemic diabetic ketoacidosis (rare but serious) 2

Agent-Specific Concerns

• Canagliflozin (not empagliflozin or dapagliflozin) associated with increased amputation risk and bone fractures 1
• Dapagliflozin showed increased bone fractures in one moderate renal impairment study (13 patients over 104 weeks vs 0 with placebo), though this has not been consistently replicated 5
• No increased amputation risk demonstrated for empagliflozin or dapagliflozin to date 1

Clinical Decision Algorithm

For Type 2 Diabetes with Established ASCVD (Prioritizing Mortality)

Choose empagliflozin 10 mg daily for strongest cardiovascular death reduction evidence 1

For Chronic Kidney Disease (eGFR 25-75 mL/min/1.73 m², UACR ≥200 mg/g)

Choose dapagliflozin 10 mg daily for most robust CKD-specific trial data and ability to initiate at eGFR ≥25 mL/min/1.73 m² 2, 3

For Heart Failure (Any Ejection Fraction, With or Without Diabetes)

Choose either dapagliflozin 10 mg daily or empagliflozin 10 mg daily based on formulary/cost—both have equivalent Class I evidence 1, 4

For eGFR 25-29 mL/min/1.73 m²

Choose dapagliflozin 10 mg daily as it has trial data supporting initiation in this range, while empagliflozin trials excluded patients with eGFR <30 mL/min/1.73 m² 2

For eGFR <25 mL/min/1.73 m²

Do not initiate either agent; consider GLP-1 receptor agonists for glycemic control and cardiovascular protection 2

Critical Safety Precautions (Apply to Both Agents)

• Withhold at least 3 days before major surgery or prolonged fasting to prevent postoperative ketoacidosis 2
• Hold during acute illness (fever, vomiting, diarrhea, reduced oral intake) to prevent diabetic ketoacidosis and volume depletion 2
• Maintain at least low-dose insulin in insulin-requiring patients even when SGLT2 inhibitor is held during illness 2
• Educate patients to check blood/urine ketones if malaise, nausea, or vomiting develops, even with normal glucose 2
• Assess volume status before initiation and correct volume depletion if present 2
• Consider reducing concurrent diuretic doses when initiating SGLT2 inhibitors 2

Common Pitfalls to Avoid

• Do not discontinue either agent solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 2
• Do not stop therapy due to initial eGFR dip of 3-5 mL/min/1.73 m² unless accompanied by signs of hypovolemia 2, 6
• Do not use ertugliflozin for heart failure—it lacks dedicated outcome trial data unlike dapagliflozin and empagliflozin 4
• Patients experiencing acute eGFR reduction >10% at 2 weeks actually had better long-term renal outcomes with slower eGFR decline compared to those without initial dip 2