Contraindications to SGLT2 Inhibitors
SGLT2 inhibitors are absolutely contraindicated in patients with a history of serious hypersensitivity reactions to the drug, severe renal impairment (eGFR <30 mL/min/1.73 m²), end-stage renal disease, or dialysis. 1, 2, 3
Absolute Contraindications
The following conditions represent absolute contraindications where SGLT2 inhibitors must not be initiated:
History of serious hypersensitivity reaction to empagliflozin, dapagliflozin, canagliflozin, or any excipients in the formulation 1, 2, 3
Severe renal impairment, end-stage renal disease (ESRD), or dialysis - Do not initiate if eGFR is below 30 mL/min/1.73 m² for dapagliflozin or below 20 mL/min/1.73 m² for empagliflozin in heart failure indications 1, 2, 3
Patients on dialysis - SGLT2 inhibitors are contraindicated in all patients receiving renal replacement therapy 1
Important Cautions and Relative Contraindications
While not absolute contraindications, the following situations require extreme caution or avoidance:
Type 1 Diabetes Mellitus
- Not approved for use in type 1 diabetes due to significantly increased risk of diabetic ketoacidosis 1
- SGLT2 inhibitors should not be used to improve glycemic control in type 1 diabetes patients 3
Pregnancy and Lactation
- Pregnancy: SGLT2 inhibitors pose potential risk to the fetus, especially during the second and third trimesters 1, 2
- Lactation: No data available; SGLT2 inhibitors are not recommended when breastfeeding 1, 2, 3
Renal Function Thresholds for Initiation
- Do not initiate empagliflozin if eGFR <45 mL/min/1.73 m² for glycemic control 2
- Do not initiate dapagliflozin if eGFR <45 mL/min/1.73 m² for glycemic control, as the drug is likely ineffective based on mechanism of action 3
- For heart failure and chronic kidney disease indications, lower eGFR thresholds apply (dapagliflozin can be initiated down to eGFR 25 mL/min/1.73 m²) 1, 3
High-Risk Situations Requiring Careful Assessment
Ketoacidosis Risk Factors
Before initiating SGLT2 inhibitors, assess for conditions that predispose to ketoacidosis 1, 2:
- Patients with reduced oral intake or prolonged fasting
- Patients scheduled for major surgery (withhold at least 3 days prior) 3
- Patients with acute illness, dehydration, or metabolic acidosis
- Patients on very low carbohydrate diets
Volume Depletion and Hypotension
Assess and correct volume status before initiating in 1, 2:
- Patients with renal impairment
- Elderly patients
- Patients with low systolic blood pressure (<100 mmHg)
- Patients on diuretics or with volume depletion
Infection Risk Considerations
Use with caution in patients at increased risk for 1:
- Genital mycotic infections - occurs in approximately 6% of users
- Urosepsis and pyelonephritis - evaluate and treat urinary tract infections promptly
- Necrotizing fasciitis of the perineum (Fournier's gangrene) - rare but life-threatening
Amputation and Bone Fracture Risk (Canagliflozin-Specific)
Exercise extreme caution or avoid canagliflozin in patients with 1:
- History of prior amputation
- Severe peripheral vascular disease
- Diabetic neuropathy
- Active diabetic foot ulcers or soft tissue infections
- History of osteoporosis (canagliflozin only)
Common Pitfalls to Avoid
Do not discontinue SGLT2 inhibitors solely because eGFR has declined below the initiation threshold - once started for cardiorenal protection, continue down to eGFR 20 mL/min/1.73 m² unless dialysis is initiated 1, 4
Do not mistake the initial reversible eGFR dip (3-5 mL/min/1.73 m² in first 4 weeks) as acute kidney injury - this hemodynamic effect is expected and does not require discontinuation 4, 5
Temporarily discontinue during acute illness with reduced oral intake, prolonged fasting, or critical medical illness to prevent ketoacidosis 1, 2, 3
Monitor for euglycemic diabetic ketoacidosis - assess patients presenting with metabolic acidosis symptoms regardless of blood glucose level 1, 2, 3