What are the contraindications for Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors?

SGLT2 Inhibitor Contraindications

SGLT2 inhibitors are contraindicated in patients with type 1 diabetes, known hypersensitivity to the drug, during lactation, and in patients on dialysis. 1

Absolute Contraindications

• Type 1 diabetes mellitus: SGLT2 inhibitors are not approved for use in patients with type 1 diabetes due to increased risk of diabetic ketoacidosis 1
• Known hypersensitivity to the specific SGLT2 inhibitor 1, 2, 3
• Patients on dialysis 1
• Lactation: No data available on safety during breastfeeding 1, 2
• Severe hepatic impairment (Child-Pugh C) - specific to some SGLT2 inhibitors 1

Renal Function Considerations

Renal function limitations vary by specific agent:

• Dapagliflozin: Not recommended for glycemic control when eGFR <45 mL/min/1.73 m² 2
• Empagliflozin: Do not initiate if eGFR <45 mL/min/1.73 m² 3
• For heart failure/CKD indications: Generally not recommended to initiate when eGFR <20 mL/min/1.73 m² 1

It's important to note that while SGLT2 inhibitors have reduced glucose-lowering efficacy at lower eGFR levels, they may still provide cardiovascular and renal benefits at eGFRs between 20-45 mL/min/1.73 m² 1.

Cautions and Relative Contraindications

Volume Status Concerns

• Volume depletion: Use with caution in patients at risk for volume depletion 1
• Low systolic blood pressure (<100 mmHg) 1
• Concomitant diuretic use: Consider reducing diuretic dose 1

Infection Risk

• History of recurrent genital mycotic infections: Increased risk of genital infections 1, 4
• History of necrotizing fasciitis of the perineum (Fournier's gangrene) 1

Surgical Considerations

• Scheduled surgery: Temporary discontinuation before scheduled surgery (3-4 days) is recommended to avoid potential risk for ketoacidosis 1

Other Cautions

• Pregnancy: Limited data available, use caution 1
• Ketoacidosis risk factors: Insulin deficiency, reduced caloric intake, excessive alcohol intake 1, 4
• Acute kidney injury: Temporarily discontinue in settings of reduced oral intake or fluid losses 3
• Urosepsis and pyelonephritis: Higher risk of urinary tract infections 1, 3

Practical Approach to SGLT2 Inhibitor Use

1. Assess renal function before initiation

   • Safe to initiate for most indications if eGFR ≥45 mL/min/1.73 m²
   • For cardiovascular/renal protection, may initiate if eGFR ≥20 mL/min/1.73 m² 1

2. Evaluate volume status and correct volume depletion before initiating

   • Particularly important in elderly patients or those on diuretics 1

3. Screen for risk factors for adverse effects:

   • History of genital infections
   • Risk factors for ketoacidosis
   • Planned surgical procedures

4. Provide patient education on:

   • Signs/symptoms of ketoacidosis
   • Genital hygiene to prevent infections
   • Sick day management
   • When to temporarily discontinue medication

Special Considerations

SGLT2 inhibitors have demonstrated significant cardiovascular and renal benefits beyond glucose control 5. Despite contraindications and cautions, their benefits on reducing major adverse cardiovascular events, heart failure hospitalizations, and CKD progression make them valuable treatment options when appropriately prescribed 1.

The initial decline in eGFR (3-5 mL/min/1.73 m²) after starting an SGLT2 inhibitor is hemodynamic in nature and generally reversible 1. This should not be a reason to discontinue therapy unless the decline is severe or persistent.