What SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitor and dose should be added to a patient's regimen?

SGLT2 Inhibitor Selection and Dosing

Dapagliflozin 10 mg once daily is the preferred SGLT2 inhibitor based on its proven cardiovascular and renal benefits across a wider range of kidney function compared to other SGLT2 inhibitors. 1, 2

Selection Rationale Based on Kidney Function

The choice of SGLT2 inhibitor depends primarily on the patient's kidney function:

For eGFR ≥45 mL/min/1.73 m²:

• Dapagliflozin: 10 mg daily
• Empagliflozin: 10 mg daily
• Canagliflozin: 100 mg daily

For eGFR 30-44 mL/min/1.73 m² (Stage 3b CKD):

• Dapagliflozin: 10 mg daily - can be used down to eGFR 25 mL/min/1.73 m²
• Canagliflozin: 100 mg daily (maximum dose)
• Empagliflozin: Not recommended for glycemic control at this level
• Ertugliflozin: Not recommended at this level

For eGFR 25-29 mL/min/1.73 m² (Stage 4 CKD):

• Dapagliflozin: Initiation not recommended below eGFR 25, but may continue 10 mg daily if already started and tolerated
• Canagliflozin: Initiation not recommended, but may continue 100 mg daily if tolerated

For eGFR <25 mL/min/1.73 m² (Stage 5 CKD):

• All SGLT2 inhibitors: Generally not recommended for initiation
• If already on therapy: Dapagliflozin may be continued until dialysis for cardiovascular and kidney benefits 1

Cardiovascular and Renal Benefits

SGLT2 inhibitors provide significant benefits beyond glycemic control:

• Reduced mortality: Empagliflozin reduces cardiovascular death by 38% (HR: 0.62; 95% CI: 0.49-0.77) 1, 3
• Reduced heart failure hospitalizations: All SGLT2 inhibitors reduce this risk by 27-35% 2, 4
• Renal protection: Slow GFR decline and reduce progression of chronic kidney disease 1, 2
• Blood pressure reduction: Modest reductions through osmotic diuresis 5
• Weight loss: 2-3 kg on average 5

Clinical Decision Algorithm

1. Assess eGFR first:

   • If eGFR ≥45 mL/min/1.73 m²: Dapagliflozin 10 mg daily
   • If eGFR 25-44 mL/min/1.73 m²: Dapagliflozin 10 mg daily (preferred due to broader eGFR range)
   • If eGFR <25 mL/min/1.73 m²: Consider alternative agents

2. Consider comorbidities:

   • Heart failure: Dapagliflozin or empagliflozin (both have specific HF indications) 1, 2
   • Established cardiovascular disease: Any SGLT2 inhibitor (all have shown benefit) 2
   • Diabetic kidney disease with albuminuria: Dapagliflozin or canagliflozin 1

3. Start at standard dose:

   • Dapagliflozin: 10 mg once daily
   • Empagliflozin: 10 mg once daily
   • Canagliflozin: 100 mg once daily (not 300 mg in renal impairment)

Important Safety Considerations

• Volume depletion: Monitor for signs of dehydration, especially in elderly patients or those on diuretics 2
• Genital mycotic infections: Increased risk, especially in women 5
• Euglycemic diabetic ketoacidosis: Rare but serious; educate patients about symptoms 2, 5
• Surgery: Discontinue SGLT2 inhibitors at least 3 days before planned surgery 2
• Drug interactions: Minimal clinically significant interactions with commonly used medications 6

Pitfalls to Avoid

• Don't use for rapid glycemic control: SGLT2 inhibitors provide modest HbA1c reductions (0.6-0.8%)
• Don't initiate in severely dehydrated patients: Correct volume status first
• Don't overlook the need to adjust other diabetes medications: May need to reduce insulin or sulfonylurea doses to prevent hypoglycemia
• Don't initiate in patients with active urinary tract infections: Resolve infection first

In summary, dapagliflozin 10 mg once daily offers the best combination of cardiovascular and renal benefits with the broadest range of kidney function tolerance among SGLT2 inhibitors, making it the preferred choice for most patients.