What are the current recommendations for sodium‑glucose co‑transporter‑2 (SGLT2) inhibitors in patients with coronary artery disease, including those with type 2 diabetes or heart‑failure, dosing, contraindications, and monitoring?

SGLT2 Inhibitors in Coronary Artery Disease

SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) are strongly recommended for all patients with coronary artery disease and type 2 diabetes to reduce major adverse cardiovascular events, cardiovascular death, and heart failure hospitalizations, independent of baseline HbA1c or concomitant glucose-lowering medications. 1, 2

Primary Indications by Patient Type

CAD Patients WITH Type 2 Diabetes

• SGLT2 inhibitors with proven cardiovascular benefit are Class I (strongest) recommendations to reduce cardiovascular events, independent of glycemic control targets 1
• These agents reduce:
  • Major adverse cardiovascular events (MACE) by 16% across the cardiometabolic disease spectrum 1
  • Cardiovascular death by 13-15% in patients with atherosclerotic cardiovascular disease 3
  • Heart failure hospitalization by 28-35% even in patients without prior heart failure history 1
  • Non-fatal myocardial infarction by 21 fewer events per 1000 patients 2
  • Non-fatal stroke by 21-25 fewer events per 1000 patients 2

CAD Patients WITHOUT Type 2 Diabetes

• SGLT2 inhibitors are NOT currently recommended for CAD patients without diabetes, as cardiovascular outcome trials enrolled predominantly diabetic populations 1, 3
• The exception is GLP-1 receptor agonist semaglutide (not an SGLT2 inhibitor), which should be considered in overweight CAD patients (BMI >27 kg/m²) without diabetes 1

Implementation Algorithm

Step 1: Verify Eligibility Criteria

Check renal function:

• eGFR must be ≥20 mL/min/1.73 m² for initiation 2
• Do NOT initiate if eGFR <45 mL/min/1.73 m² per FDA labeling 4
• Discontinue if eGFR falls persistently below 45 mL/min/1.73 m² 4

Exclude absolute contraindications:

• Type 1 diabetes 2, 4
• History of serious hypersensitivity to the agent 2, 4
• Severe renal impairment, end-stage renal disease, or dialysis 4

Step 2: Select Specific Agent

All three FDA-approved agents are appropriate for CAD patients: 2

• Empagliflozin 10 mg once daily (may increase to 25 mg) - demonstrated 35% reduction in heart failure hospitalization in EMPA-REG OUTCOME 1
• Canagliflozin - showed 39% reduction in heart failure hospitalization in CREDENCE trial 1
• Dapagliflozin - consistent cardiovascular benefits across trials 1

Agent-specific considerations:

• Avoid canagliflozin in patients with severe peripheral vascular disease, neuropathy, or diabetic foot ulcers due to increased amputation risk 2
• Use caution with canagliflozin in patients with osteoporosis due to increased fracture risk 2

Step 3: Adjust Concomitant Medications BEFORE Initiation

Reduce hypoglycemia risk:

• Decrease insulin or sulfonylurea doses by approximately 50% when initiating SGLT2 inhibitors 2

Prevent volume depletion:

• Assess volume status before initiating in elderly patients, those with low systolic blood pressure, renal impairment, or on diuretics 4
• Consider reducing diuretic doses in patients at risk for volume depletion 2

Step 4: Monitor Initial Response (First 4 Weeks)

Expected hemodynamic changes:

• Anticipate a reversible eGFR decline of 3-5 mL/min/1.73 m² - this is hemodynamic and not harmful 2
• Do not discontinue for this expected decline unless eGFR falls below 45 mL/min/1.73 m² persistently 4

Monitor for volume depletion signs:

• Hypotension, dizziness, orthostatic symptoms 4

Special Populations Requiring Intensified Monitoring

CAD Patients with Reduced LVEF (≤40%)

• SGLT2 inhibitors are MANDATORY unless contraindicated - this represents a quality measure per 2024 ACC/AHA guidelines 2
• Class I recommendation to reduce cardiovascular death and heart failure hospitalization regardless of diabetes status 2

CAD Patients with Heart Failure and Preserved EF (>40%)

• Class 2a recommendation to decrease heart failure hospitalizations 2
• Empagliflozin demonstrated 21% reduction in composite cardiovascular death or heart failure hospitalization in EMPEROR-Preserved trial 1

CAD Patients with Chronic Kidney Disease

• Strong Class 1 recommendation for CKD with albuminuria ≥200 mg/g 2
• Class 2B recommendation for UACR <200 mg/g 2
• SGLT2 inhibitors reduce progression of diabetic kidney disease 2
• In extensive CAD populations, SGLT2 inhibitors were associated with less renal function deterioration over 3-year follow-up 5

Critical Safety Protocols

Euglycemic Diabetic Ketoacidosis (DKA) Prevention

Implement "STOP DKA" protocol education: 2

• Temporarily discontinue SGLT2 inhibitors during:
  • Prolonged fasting or surgery
  • Severe illness with reduced oral intake
  • Excessive alcohol intake
  • Situations causing significant fluid losses

Assess for DKA regardless of blood glucose level if patients present with metabolic acidosis symptoms 4

Acute Kidney Injury Prevention

• Temporarily discontinue during settings of reduced oral intake or significant fluid losses 4
• If acute kidney injury occurs, discontinue immediately and treat promptly 4

Genitourinary Infections

• Monitor for urinary tract infections and genital mycotic infections (occur in ≥5% of patients) 4
• Female genital mycotic infections are particularly common 4
• Evaluate and treat urosepsis or pyelonephritis promptly if suspected 4

Dosing Specifications

Standard initiation: 4

• Start with 10 mg once daily in the morning, with or without food
• May increase to 25 mg once daily for additional glycemic benefit if tolerated

No dose adjustment needed for: 4

• Mild to moderate hepatic impairment
• eGFR ≥45 mL/min/1.73 m²

Evidence Strength Considerations

The cardiovascular benefits of SGLT2 inhibitors in CAD are supported by:

• Multiple large randomized controlled trials including EMPA-REG OUTCOME, CANVAS, and CREDENCE 1
• Meta-analyses demonstrating consistent 28-32% reduction in first heart failure hospitalization across cardiometabolic disease states 3
• Real-world observational data showing 68% reduction in all-cause mortality (HR 0.32) in patients with extensive CAD over 3-year follow-up 5

Important caveat: Lesser cardiovascular benefits were observed with ertugliflozin compared to empagliflozin, canagliflozin, and dapagliflozin, suggesting cardiovascular protection is not a uniform class effect 1