What SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitor will I start for a patient with type 2 diabetes?

SGLT2 Inhibitor Selection for Type 2 Diabetes

Empagliflozin is the preferred SGLT2 inhibitor for patients with type 2 diabetes due to its robust cardiovascular benefits, established renal protection, and favorable safety profile. 1, 2

First-Line SGLT2 Inhibitor Options

• Empagliflozin (10 mg daily) is the preferred first-line SGLT2 inhibitor due to its demonstrated 38% relative risk reduction in cardiovascular death and 35% reduction in hospitalization for heart failure in patients with established cardiovascular disease 2
• Canagliflozin (100 mg daily) is an alternative option with proven cardiovascular and renal benefits, particularly for patients with diabetic nephropathy with albuminuria 3
• Dapagliflozin (10 mg daily) can be considered, especially in patients with heart failure 1

Decision Algorithm Based on Patient Characteristics

For patients with established cardiovascular disease:

• Empagliflozin is preferred due to its superior cardiovascular mortality reduction (38% relative risk reduction) 2, 1

For patients with diabetic nephropathy with albuminuria:

• Either empagliflozin or canagliflozin can be used, as both have demonstrated significant renal protection 4, 3
• Empagliflozin showed 44% relative risk reduction in doubling of serum creatinine and 55% reduction in initiation of renal replacement therapy 4

For patients with heart failure:

• Empagliflozin or dapagliflozin are preferred options 1

Dosing Considerations

• Start empagliflozin at 10 mg once daily 5
• Start canagliflozin at 100 mg once daily 3
• SGLT2 inhibitors can be initiated in patients with eGFR ≥20 ml/min/1.73 m² 1
• Once initiated, SGLT2 inhibitors can be continued at lower eGFR levels 1

Safety Considerations and Monitoring

• Monitor for genital mycotic infections - counsel on genital hygiene 1
• Watch for volume depletion, especially in patients on diuretics or with tenuous volume status 1
• Be alert for euglycemic diabetic ketoacidosis, especially in insulin-dependent patients 1
• Canagliflozin has specific cautions regarding increased risk of amputation and bone fractures 1
• Empagliflozin and dapagliflozin have not shown increased amputation risk 1

Special Precautions

• Implement sick day protocol: temporarily withhold SGLT2 inhibitor during acute illness 1
• Withhold SGLT2 inhibitor at least 3 days prior to surgery or procedures requiring prolonged fasting 3
• Adjust doses of concurrent insulin or sulfonylureas to reduce hypoglycemia risk 1
• Anticipate an initial acute drop in eGFR, which is generally not a reason to discontinue therapy 1

Key Pitfalls to Avoid

• Do not use SGLT2 inhibitors in patients with type 1 diabetes 1, 5
• Avoid initiating in patients with severe renal impairment (eGFR <20 ml/min/1.73 m²) 1
• Be cautious with canagliflozin in patients with history of prior amputation, severe peripheral vascular disease, neuropathy, or diabetic foot ulcers 1
• Do not use during pregnancy or breastfeeding 3

By following this evidence-based approach to SGLT2 inhibitor selection, you can optimize cardiovascular and renal outcomes while minimizing adverse effects in patients with type 2 diabetes.