What is a better SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitor to initiate for therapy in this patient?

Selecting the Optimal SGLT2 Inhibitor for Therapy Initiation

Based on the most recent evidence, empagliflozin or dapagliflozin are preferred SGLT2 inhibitors for initiation due to their proven cardiovascular and renal benefits with robust safety profiles across a wider range of eGFR values.

Comparing Available SGLT2 Inhibitors

Cardiovascular Benefits

• Empagliflozin has demonstrated significant reduction in cardiovascular death and hospitalization for heart failure in patients with HFrEF, regardless of diabetes status 1, 2
• Dapagliflozin reduced the risk of worsening heart failure or death from cardiovascular causes in patients with reduced ejection fraction, with benefits seen in both diabetic and non-diabetic patients 3
• Canagliflozin has shown cardiovascular benefits but carries additional warnings about lower limb amputation risk that are not present with empagliflozin or dapagliflozin 4, 5

Renal Considerations

• SGLT2 inhibitors can be initiated in patients with eGFR ≥20 ml/min/1.73 m² and continued at lower levels of eGFR 1
• Dapagliflozin has proven kidney benefits with evidence supporting initiation in patients with eGFR ≥25 ml/min/1.73 m² 1
• Empagliflozin has demonstrated efficacy and safety in patients with eGFR ≥20 ml/min/1.73 m² 1
• Canagliflozin is not recommended for initiation in patients with eGFR <30 ml/min/1.73 m² for glycemic control, though it may be continued at 100 mg daily for kidney and CV benefit if already tolerated 1, 4

Safety Profile Differences

• Canagliflozin carries specific warnings about increased risk of lower-extremity amputations and bone fractures not seen with other SGLT2 inhibitors 1, 4, 5
• All SGLT2 inhibitors share common side effects including:
  • Genital mycotic infections 1
  • Risk of volume depletion 1
  • Potential for euglycemic diabetic ketoacidosis 1, 6
• Rare but serious adverse events have been reported with specific agents, such as pancreatitis with empagliflozin in isolated case reports 7

Decision Algorithm for SGLT2 Inhibitor Selection

1. For patients with heart failure with reduced ejection fraction (HFrEF):

   • Prefer empagliflozin or dapagliflozin based on their robust evidence in HFrEF populations 1, 3

2. For patients with chronic kidney disease:

   • If eGFR 20-29 ml/min/1.73 m²: Choose empagliflozin or dapagliflozin (not canagliflozin) 1
   • If eGFR ≥30 ml/min/1.73 m²: Any SGLT2 inhibitor is appropriate, but empagliflozin or dapagliflozin may be preferred due to more extensive evidence 1

3. For patients with established atherosclerotic cardiovascular disease:

   • Any SGLT2 inhibitor with proven CV benefit is appropriate 1
   • Consider avoiding canagliflozin in patients with peripheral vascular disease or neuropathy due to amputation risk 4, 5

4. For patients with history of or risk factors for amputation:

   • Avoid canagliflozin and choose empagliflozin or dapagliflozin instead 1, 4

Implementation Considerations

• SGLT2 inhibitors can be initiated in both inpatient and outpatient settings according to ACC/AHA guidelines 1
• For hospitalized patients with heart failure, SGLT2 inhibitors can be safely initiated before discharge 1
• Dose adjustments may be necessary based on renal function 1
• Monitor for common adverse effects including:
  • Genital mycotic infections (counsel on genital hygiene) 1
  • Volume depletion (consider proactive dose reduction of diuretics in high-risk patients) 1
  • Diabetic ketoacidosis (educate about signs/symptoms) 1

Common Pitfalls to Avoid

• Failure to adjust concomitant medications: Consider reducing doses of diuretics or insulin when initiating SGLT2 inhibitors to prevent hypotension or hypoglycemia 1
• Inappropriate discontinuation after initial eGFR decline: SGLT2 inhibitors cause a reversible decline in eGFR that does not require discontinuation and may actually protect against acute kidney injury 1
• Overlooking sick day protocols: Patients should be educated to temporarily hold SGLT2 inhibitors during acute illness to prevent ketoacidosis 1
• Neglecting amputation risk with canagliflozin: Patients with peripheral vascular disease, neuropathy, or history of amputations should avoid canagliflozin 4, 5