Can dapagliflozin be used instead of empagliflozin in a 40‑year‑old woman with type 2 diabetes mellitus, hemoglobin A1c 13.5%, who follows a ketogenic low‑carbohydrate diet?

Can Dapagliflozin Be Used Instead of Empagliflozin?

Yes, dapagliflozin can be used in place of empagliflozin for this patient, but with critical caveats regarding the ketogenic diet and renal function monitoring. Both SGLT2 inhibitors provide equivalent cardiovascular and renal protection, but the ketogenic diet creates a substantial risk for euglycemic diabetic ketoacidosis that requires immediate dietary modification before starting either agent. 1, 2

Equivalence of SGLT2 Inhibitors for Cardiovascular and Renal Protection

• Empagliflozin and dapagliflozin demonstrate no significant difference in 6-year cardiovascular outcomes (major adverse cardiovascular events: myocardial infarction, ischemic stroke, heart failure, or cardiovascular death) in adults with treated type 2 diabetes, with a risk ratio of 1.00 (95% CI 0.91–1.11). 3

• Both agents reduce cardiovascular death by approximately 26–38% in patients with type 2 diabetes and established cardiovascular disease, with empagliflozin showing a 38% relative risk reduction and dapagliflozin demonstrating a 29% reduction in cardiovascular death or heart failure hospitalization. 1, 4

• Dapagliflozin reduces the composite of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death by 39% (HR 0.61,95% CI 0.51–0.72), with kidney-specific outcomes improved by 44% (HR 0.56,95% CI 0.45–0.68). 1

• The standard therapeutic dose is 10 mg once daily for both dapagliflozin and empagliflozin when used for cardiovascular or renal protection, with no titration required. 1, 4

Critical Safety Concern: Ketogenic Diet and Diabetic Ketoacidosis Risk

• The ketogenic low-carbohydrate diet is a major precipitating factor for euglycemic diabetic ketoacidosis (DKA) in patients taking SGLT2 inhibitors, and this dietary pattern must be discontinued before initiating either dapagliflozin or empagliflozin. 2

• Euglycemic DKA can occur even when blood glucose is normal or only slightly elevated (<200 mg/dL), presenting with nonspecific symptoms including nausea, vomiting, abdominal pain, tiredness, and labored breathing. 1, 4, 2

• Educate the patient that ketogenic diets, reduced caloric intake, insulin dose reduction, infection, dehydration, and alcohol abuse are all precipitating factors for ketoacidosis when taking SGLT2 inhibitors. 2

• If symptoms of ketoacidosis occur (malaise, nausea, vomiting, abdominal pain, dyspnea), the patient must discontinue the SGLT2 inhibitor immediately and seek urgent medical attention, even if blood glucose is normal. 1, 2

Renal Function Considerations for This Patient

• With an HbA1c of 13.5%, immediate dual therapy with metformin and basal insulin is required because SGLT2 inhibitors alone lower HbA1c by only 0.5–0.8%, which is insufficient to achieve target control from this baseline. 5

• Dapagliflozin can be initiated for cardiovascular and renal protection when eGFR ≥25 mL/min/1.73 m², but its glucose-lowering efficacy is markedly reduced when eGFR <45 mL/min/1.73 m². 1, 2

• For glycemic control as the primary indication, dapagliflozin should not be initiated when eGFR <45 mL/min/1.73 m² because it is likely ineffective based on its mechanism of action. 1, 2

• Check eGFR before starting dapagliflozin and recheck within 1–2 weeks after initiation; an acute, reversible eGFR dip of 2–5 mL/min/1.73 m² is expected and should not prompt discontinuation. 1

Practical Switching Protocol When Empagliflozin Is Unavailable

• Stop the ketogenic diet immediately and transition to a balanced, moderate-carbohydrate meal plan (45–60 grams of carbohydrate per meal) to eliminate the primary DKA risk factor. 2

• Assess volume status before initiating dapagliflozin; correct any volume depletion and consider reducing concurrent diuretic doses if the patient is on loop or thiazide diuretics. 1, 2

• Start dapagliflozin 10 mg once daily for cardiovascular and renal protection, regardless of baseline eGFR (as long as ≥25 mL/min/1.73 m²). 1, 2

• Simultaneously initiate metformin 500 mg twice daily with meals and basal insulin 10 units at bedtime (or 0.2 units/kg given the HbA1c of 13.5%) to achieve adequate glycemic control, because SGLT2 inhibitors alone cannot reduce HbA1c from 13.5% to target. 5

• Titrate metformin to 2000 mg daily (1000 mg twice daily) over 2–3 weeks and increase basal insulin by 2–4 units every 3 days until fasting glucose reaches 80–130 mg/dL. 5

Comparative Efficacy Data Between Dapagliflozin and Empagliflozin

• In a retrospective study of patients switching from dapagliflozin to empagliflozin, 70.3% maintained or improved glycemic control at 6 months, with no significant difference in renal function (eGFR) between baseline and follow-up. 6

• A randomized controlled trial comparing empagliflozin 25 mg versus dapagliflozin 10 mg over 12 weeks showed empagliflozin caused a slightly greater reduction in fasting blood sugar (–75.6 mg/dL vs. –63.5 mg/dL, p=0.001) and HbA1c (–1.7% vs. –1.2%, p=0.002), but both drugs had excellent efficacy and safety profiles. 7

• The tolerability profile of both drugs is comparable, with minor differences in urinary and genital infection rates (empagliflozin 2.3–3.1% vs. dapagliflozin 7.1–8.7%). 7

Monitoring and Safety Precautions

• Genital mycotic infections occur in approximately 6% of dapagliflozin users versus 1% with placebo; counsel the patient on daily hygiene measures to reduce this risk. 1, 2

• Warn about the risk of urinary tract infections, which may be serious; advise the patient to seek medical attention promptly if symptoms of dysuria, frequency, or fever develop. 2

• Withhold dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 1, 4

• Temporarily discontinue dapagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea, and maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held. 1

Contraindications to Dapagliflozin in This Patient

• Dapagliflozin is absolutely contraindicated during pregnancy and breastfeeding due to potential fetal toxicity and absence of lactation safety data. 4

• Patients receiving chronic dialysis or with a documented serious hypersensitivity reaction to any SGLT2 inhibitor should not receive dapagliflozin. 4

• Dapagliflozin is not approved for type 1 diabetes mellitus because it markedly increases the risk of diabetic ketoacidosis. 4, 2

Key Pitfalls to Avoid

• Do not initiate dapagliflozin while the patient continues a ketogenic diet; this combination creates an unacceptable risk of euglycemic DKA. 2

• Do not use dapagliflozin as monotherapy for an HbA1c of 13.5%; immediate dual therapy with metformin and basal insulin is required to achieve adequate glycemic control. 5

• Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist despite loss of glycemic efficacy. 1

• Do not stop dapagliflozin in response to the expected early eGFR dip of 2–5 mL/min/1.73 m² within the first 2–4 weeks; this change is hemodynamic and reversible. 1

• Do not reduce the dapagliflozin dose below 10 mg for cardiovascular or renal indications, even at lower eGFR levels; all outcome trials used the fixed 10 mg dose. 1