What are the contraindications for dapagliflozin (e.g., type 1 diabetes mellitus, risk of diabetic ketoacidosis, severe renal impairment with estimated glomerular filtration rate < 30 mL/min/1.73 m² or chronic dialysis, known hypersensitivity, pregnancy, breastfeeding)?

Contraindications for Dapagliflozin

Dapagliflozin is absolutely contraindicated in patients on dialysis, those with known hypersensitivity to the drug, and during pregnancy and lactation. 1

Absolute Contraindications

• Dialysis: Patients on chronic dialysis should not receive dapagliflozin under any circumstances. 1

• Known hypersensitivity: History of serious hypersensitivity reaction to dapagliflozin or any SGLT2 inhibitor is an absolute contraindication. 1, 2

• Pregnancy: Dapagliflozin is contraindicated during pregnancy due to potential fetal harm. 1

• Lactation: No safety data exist for breastfeeding mothers; dapagliflozin should not be used. 1

Type 1 Diabetes Mellitus

• Not approved for type 1 diabetes: Dapagliflozin carries significantly increased risk of diabetic ketoacidosis in type 1 diabetes and is not approved for this indication. 1

• The European regulatory authority withdrew authorization for type 1 diabetes use due to ketoacidosis risk. 3

• Post-hoc analyses in type 1 diabetes showed increased ketoacidosis events despite some glycemic benefit. 4

Severe Renal Impairment Thresholds

For Glycemic Control

• Do not initiate if eGFR <45 mL/min/1.73 m² when the primary goal is glucose lowering, as the drug becomes ineffective due to its mechanism of action. 1, 5

For Cardiovascular/Renal Protection

• Do not initiate if eGFR <25 mL/min/1.73 m² for heart failure or chronic kidney disease indications. 1, 5

• Some recent guidelines support initiation down to eGFR ≥20 mL/min/1.73 m² for cardiovascular and renal protection based on the EMPA-KIDNEY trial data with sister SGLT2 inhibitors. 5

• If already on treatment, continue dapagliflozin 10 mg daily even if eGFR falls below 25 mL/min/1.73 m² until dialysis is required. 5

Critical Clinical Caveats

Diabetic Ketoacidosis Risk

• Dapagliflozin carries risk of euglycemic diabetic ketoacidosis (DKA with normal or near-normal glucose <200 mg/dL), which can occur even in type 2 diabetes. 1, 5, 2

• Withhold dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 5, 2

• Temporarily discontinue during acute illness with reduced oral intake, fever, vomiting, or diarrhea. 5

• Dapagliflozin showed 12-fold higher reporting frequency of ketoacidosis compared to DPP-4 inhibitors and 7.6-fold higher than insulins in European pharmacovigilance data. 3

Volume Depletion Precautions

• Use extreme caution (not absolute contraindication) in patients with low systolic blood pressure, concurrent diuretic therapy, or age ≥75 years due to volume depletion risk. 1, 5

• Assess and correct volume status before initiation; consider reducing concurrent diuretic doses. 5

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glucose-lowering efficacy is lost. 5

• Do not stop for the expected initial eGFR dip of 2–5 mL/min/1.73 m² within the first 2–4 weeks, which is hemodynamic and reversible. 5

• Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held during illness, as complete insulin cessation dramatically increases DKA risk. 5