What are the contraindications for Sodium-Glucose Linked Transporter 2 (SGLT-2) inhibitors in patients with a history of severe kidney disease, genital mycotic infections, or hypotension?

Contraindications for SGLT-2 Inhibitors

SGLT-2 inhibitors have only two absolute contraindications: a history of serious hypersensitivity reaction to the drug and severe renal impairment with eGFR <30 mL/min/1.73 m² or patients on dialysis. 1, 2, 3

Absolute Contraindications

• History of serious hypersensitivity reaction to the specific SGLT-2 inhibitor (e.g., angioedema) 1, 2, 3
• Severe renal impairment: eGFR <30 mL/min/1.73 m² 1, 2
• End-stage renal disease (ESRD) 1
• Patients on dialysis 1

Important nuance: The 2024 BMJ guideline clarifies that SGLT-2 inhibitors should generally not be newly initiated with eGFR <20 mL/min/1.73 m², but may be continued even if eGFR drops below this threshold for individuals already on therapy until dialysis initiation. 1 The 2025 KDOQI commentary supports this approach, noting that dapagliflozin's FDA label no longer requires discontinuation at dialysis initiation based on safety data. 1

Clinical Situations Requiring Caution (Not Absolute Contraindications)

Severe Kidney Disease Context

• History of genital mycotic infections: This is NOT a contraindication. 1 Genital mycotic infections occur in approximately 6% of patients on SGLT-2 inhibitors versus 1% on placebo, but most are mild and respond to standard antifungal therapy without requiring drug discontinuation. 4, 5, 6
• Hypotension or volume depletion risk: This is NOT a contraindication. 1 Exercise caution in patients with renal impairment, low systolic blood pressure, those on diuretics, or elderly patients due to risk of intravascular volume contraction. 1, 2, 3

Temporary Withholding Situations

Withhold SGLT-2 inhibitors temporarily (but do not permanently discontinue) in these clinical situations: 1, 2, 3

• Prolonged fasting due to acute illness or surgery 1, 2, 3
• Critical medical illness when patients may be at greater risk for ketosis 1, 2
• Reduced oral intake (such as acute illness or fasting) 2, 3
• Fluid losses (such as gastrointestinal illness or excessive heat exposure) 2

Resume SGLT-2 inhibitors when the patient is clinically stable and has resumed oral intake. 3

Drug-Specific Cautions (Not Contraindications)

Canagliflozin and Ertugliflozin Specific

• History of prior amputation, severe peripheral vascular disease, neuropathy, or diabetic foot ulcers requires caution with canagliflozin and ertugliflozin specifically 1
• History of osteoporosis requires caution with canagliflozin due to increased bone fracture risk 1

Empagliflozin and Dapagliflozin

• No increased risk of amputation has been seen for empagliflozin or dapagliflozin to date 1

Common Pitfalls to Avoid

Do not discontinue SGLT-2 inhibitors for:

• Genital mycotic infections: Treat with standard antifungal therapy and continue the SGLT-2 inhibitor 4, 5, 6
• Mild to moderate urinary tract infections: Continue SGLT-2 inhibitor during standard antibiotic treatment 7, 6
• Initial eGFR dip of 3-5 mL/min/1.73 m² in the first 4 weeks, which is expected and reversible 1, 7
• History of recurrent UTIs: Large randomized trials show no increased UTI risk with SGLT-2 inhibitors 7

Only discontinue immediately for:

• Fournier's gangrene (necrotizing fasciitis of the perineum) 4, 5, 3
• Severe or recurrent genitourinary infections that are persistent despite treatment 4, 5
• Confirmed ketoacidosis (discontinue promptly, evaluate, and treat; monitor for resolution before restarting) 2, 3

Type 1 Diabetes Consideration

SGLT-2 inhibitors are not indicated for treatment of type 1 diabetes mellitus. 1