What is the preferred SGLT2 (Sodium-Glucose Linked Transporter 2) agent for a patient with diabetes?

Preferred SGLT2 Inhibitor Selection for Diabetes Management

For patients with diabetes, dapagliflozin is the preferred SGLT2 inhibitor due to its strongest evidence for reducing CKD progression and cardiovascular events, with proven benefits at eGFR as low as 20 mL/min/1.73 m².

Patient Assessment for SGLT2 Inhibitor Selection

When selecting an SGLT2 inhibitor, consider these key factors:

1. Renal Function:

   • eGFR ≥20 mL/min/1.73 m²: Dapagliflozin preferred 1
   • eGFR <20 mL/min/1.73 m²: Switch to GLP-1 RA (dulaglutide, semaglutide, or liraglutide) 2

2. Cardiovascular Status:

   • Established ASCVD: Empagliflozin, dapagliflozin, or canagliflozin 2
   • Heart failure: Dapagliflozin (strongest evidence for HFrEF and HFpEF) 2, 1

3. Renal Status:

   • CKD with albuminuria: Dapagliflozin or canagliflozin 2, 1
   • Dapagliflozin showed 39% reduction in CKD progression and CV events 1

Algorithm for SGLT2 Inhibitor Selection

Step 1: Assess eGFR

• If eGFR ≥20 mL/min/1.73 m²: Proceed with SGLT2 inhibitor
• If eGFR <20 mL/min/1.73 m²: Use GLP-1 RA instead 2

Step 2: Evaluate Comorbidities

• Heart Failure Present:

  • Choose dapagliflozin 10 mg daily (strongest evidence) 2, 1

• CKD with Albuminuria:

  • Choose dapagliflozin 10 mg daily (primary choice) 1
  • Alternative: canagliflozin 100 mg daily 3

• Established ASCVD without HF or CKD:

  • Choose empagliflozin 10 mg daily 2, 4
  • Alternatives: dapagliflozin 10 mg or canagliflozin 100 mg 2

• Diabetes without CV/Renal Disease:

  • Any SGLT2 inhibitor can be used, with dapagliflozin preferred for its broader evidence base 1

Dosing Considerations

• Dapagliflozin: 10 mg once daily (no dose adjustment needed for renal function) 1
• Canagliflozin: 100 mg once daily (do not increase to 300 mg if eGFR <60 mL/min/1.73 m²) 3
• Empagliflozin: 10 mg once daily 4

Important Safety Considerations

• Initial eGFR Dip: Expect 3-5 mL/min/1.73 m² decrease initially; don't discontinue as this is hemodynamic and typically stabilizes 2, 5

• Volume Depletion Risk: Assess hydration status before starting; consider reducing diuretic doses 2

• Hypoglycemia Risk: Reduce insulin or sulfonylurea doses when starting SGLT2 inhibitor 2, 1

• Genital Mycotic Infections: Counsel patients on hygiene and monitoring 2

• Diabetic Ketoacidosis: Withhold during illness or procedures requiring fasting 1

Clinical Pearls

• SGLT2 inhibitors provide cardiorenal benefits independent of their glucose-lowering effects 6, 7

• For patients with multiple indications (e.g., CKD + HF), dapagliflozin offers the most comprehensive evidence base 1

• Continue SGLT2 inhibitors even when adding insulin therapy for their cardiorenal protective effects 2

• Withhold SGLT2 inhibitors at least 3 days before surgical procedures requiring fasting 3

• The benefits of SGLT2 inhibitors extend beyond glycemic control to include weight loss, blood pressure reduction, and cardiorenal protection 8, 9