What are the contraindications for Dapagliflozin (SGLT2 inhibitor)?

Dapagliflozin Contraindications

The only absolute contraindication to dapagliflozin is a history of serious hypersensitivity reaction (including anaphylaxis or angioedema) to dapagliflozin or any of its excipients. 1

Absolute Contraindication

• History of serious hypersensitivity reaction to dapagliflozin or any excipients, including anaphylaxis and angioedema 1

Important Clinical Situations Where Dapagliflozin Should NOT Be Initiated

While not absolute contraindications per FDA labeling, the following represent situations where initiation is not recommended:

Renal Function Thresholds

• eGFR <25 mL/min/1.73 m²: Do not initiate dapagliflozin 1, 2

  • However, if eGFR falls below 25 mL/min/1.73 m² during treatment, continuation at 10 mg daily is acceptable for cardiovascular and renal protection until dialysis 1, 2

• eGFR <45 mL/min/1.73 m² for glycemic control: Not recommended for initiation when the goal is improving blood glucose, as the drug is likely ineffective due to its mechanism of action 1, 2

  • Note: This is NOT a contraindication for cardiovascular or renal protection indications 1, 2

Type 1 Diabetes Mellitus

• Dapagliflozin is not indicated for glycemic control in type 1 diabetes due to markedly increased risk of diabetic ketoacidosis (DKA), a life-threatening event 1
• The risk of ketoacidosis is significantly elevated compared to placebo in type 1 diabetes patients 1

Critical Warnings and Precautions (Not Contraindications)

Diabetic Ketoacidosis Risk

• Withhold dapagliflozin at least 3 days before major surgery or procedures with prolonged fasting to prevent postoperative ketoacidosis 1, 3, 2
• Temporarily withhold during acute illness, reduced caloric intake, ketogenic diet, volume depletion, or alcohol abuse 1
• Risk factors for ketoacidosis include: type 2 diabetes with insulin deficiency, pancreatic disorders (pancreatitis history, pancreatic surgery), under-insulinization, acute febrile illness 1

Volume Depletion and Hypotension

• Use caution in patients with renal impairment, low systolic blood pressure, those on diuretics, or elderly patients due to risk of intravascular volume contraction 3
• Assess volume status before initiation and correct volume depletion if present 2

Genital Mycotic Infections

• Increased risk of genital mycotic infections; avoid use in high-risk individuals 3
• Rare but serious: necrotizing fasciitis of the perineum (Fournier gangrene) requires prompt treatment if suspected 3

Special Populations

• Pregnancy and breastfeeding: Contraindicated per general SGLT2 inhibitor guidance 4
• Dialysis patients: Not recommended for initiation 1

Key Distinction: Glycemic Control vs. Cardiovascular/Renal Protection

The renal function thresholds differ based on indication 1, 2:

• For glycemic control: Not recommended if eGFR <45 mL/min/1.73 m² (ineffective) 1
• For cardiovascular/renal protection: Can initiate if eGFR ≥25 mL/min/1.73 m² 1, 2
• Continuation: May continue 10 mg daily even if eGFR falls below 25 mL/min/1.73 m² during treatment 1, 2