What are the criteria for prescribing Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors to a patient with type 2 diabetes and a history of cardiovascular disease, heart failure, or chronic kidney disease?

SGLT2 Inhibitor Prescribing Criteria

SGLT2 inhibitors should be initiated in patients with type 2 diabetes and eGFR ≥20 mL/min/1.73 m² who have any of the following: established cardiovascular disease, heart failure, or chronic kidney disease with albuminuria ≥200 mg/g, independent of glycemic control or HbA1c level. 1, 2

Primary Indications (Class I, Level A Recommendations)

Chronic Kidney Disease

• Initiate when eGFR ≥20 mL/min/1.73 m² AND UACR ≥200 mg/g creatinine to reduce CKD progression and cardiovascular events 1, 2
• High-priority features include albuminuria ≥200 mg/g (≥20 mg/mmol), though benefit extends to UACR ≥30 mg/g 1
• Continue therapy even if eGFR falls below 20 mL/min/1.73 m² until dialysis initiation 1, 2
• The 2023 ADA/KDIGO guidelines lowered the eGFR threshold from ≥25-30 to ≥20 mL/min/1.73 m² based on DAPA-CKD and EMPEROR trial subgroup analyses 1, 2

Heart Failure

• All patients with heart failure (HFrEF or HFpEF) and type 2 diabetes should receive SGLT2 inhibitors regardless of ejection fraction 1, 3
• Particularly prioritize in heart failure with reduced ejection fraction (LVEF ≤40%) to reduce hospitalization for heart failure, MACE, and cardiovascular death 1, 3

Established Atherosclerotic Cardiovascular Disease

• Patients with established ASCVD and type 2 diabetes should receive SGLT2 inhibitors to reduce MACE, hospitalization for heart failure, and cardiovascular death 1
• The decision to treat should be made independently of baseline HbA1c or individualized HbA1c target 1

Dosing Algorithm

Standard Dosing (No Titration Required)

• Dapagliflozin: 10 mg once daily 2, 4
• Empagliflozin: 10 mg once daily (can increase to 25 mg for additional glycemic control, but 10 mg provides full cardiovascular/renal protection) 2
• Canagliflozin: 100 mg once daily 2

eGFR-Based Initiation Criteria

• eGFR ≥45 mL/min/1.73 m²: Initiate for glycemic control, cardiovascular protection, or renal protection 1, 4
• eGFR 20-44 mL/min/1.73 m²: Initiate for cardiovascular/renal protection only (glucose-lowering efficacy reduced but cardiovascular and renal benefits preserved) 1, 2
• eGFR <20 mL/min/1.73 m²: Do not initiate, but continue if already on therapy until dialysis 1, 2

Pre-Initiation Assessment

Required Evaluations

• Check eGFR and UACR 1, 2
• Assess volume status and consider reducing loop/thiazide diuretics in patients at risk for hypovolemia 1, 2
• If on insulin or sulfonylurea with well-controlled A1C, reduce insulin dose by 20% or sulfonylurea dose by 50% to prevent hypoglycemia 1

Anticipate Initial eGFR Dip

• Expect a reversible 3-5 mL/min/1.73 m² decline in eGFR within first 4 weeks, which is hemodynamic (not nephrotoxic) and not an indication to discontinue 2, 4
• This initial dip is followed by long-term eGFR stabilization and slower decline 1, 2

Contraindications and Precautions

Absolute Contraindications

• Dialysis or end-stage renal disease 1, 3
• Kidney transplant recipients 2
• Polycystic kidney disease 2
• History of serious hypersensitivity reaction 3

Relative Contraindications (Use Caution)

• History of recurrent genital candidiasis 1
• History of diabetic ketoacidosis 1
• Significant peripheral arterial disease, prior amputation, severe neuropathy, or diabetic foot ulcers (avoid canagliflozin specifically) 1
• History of osteoporosis (avoid canagliflozin) 1

Monitoring After Initiation

Initial Monitoring

• Check eGFR and potassium 1-2 weeks after starting 1, 2
• Monitor for genital mycotic infections (6% vs 1% placebo) 1, 2
• Assess for volume depletion symptoms (lightheadedness, orthostasis, weakness) 1

Ongoing Monitoring

• Continue monitoring eGFR as clinically indicated 1
• Do NOT discontinue if eGFR falls below 45 mL/min/1.73 m², as cardiovascular and renal benefits persist 1, 2

Combination Therapy Recommendations

With RAS Inhibitors

• Continue ACE inhibitors/ARBs as background therapy 1, 2
• Do not withhold RAS inhibitors when starting SGLT2 inhibitors 2

With Mineralocorticoid Receptor Antagonists

• Consider adding nonsteroidal MRA (finerenone) for patients with persistent albuminuria ≥30 mg/g despite maximal RAS inhibition and SGLT2 inhibitor use 1, 2
• SGLT2 inhibitors may reduce hyperkalemia risk when combined with MRAs 1

With GLP-1 Receptor Agonists

• Combine for additional cardiovascular protection in diabetes 1
• Benefits appear additive 1

Critical Safety Precautions

Sick Day Management

• Withhold SGLT2 inhibitors during acute illness with reduced oral intake, fever, vomiting, or diarrhea 1, 4
• Withhold at least 3 days before major surgery or procedures requiring prolonged fasting 1, 4
• Monitor for euglycemic diabetic ketoacidosis even with normal blood glucose 1, 4

Patient Education Requirements

• Counsel about genital mycotic infection symptoms and prevention 1
• Educate about diabetic ketoacidosis symptoms (nausea, vomiting, weakness) that can occur even with glucose 150-250 mg/dL 1
• Instruct on foot care (particularly with canagliflozin) 1

Common Pitfalls to Avoid

• Do not discontinue SGLT2 inhibitors when eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal benefits persist even when glycemic efficacy is lost 1, 2, 4
• Do not wait for "optimal" glycemic control before initiating—benefits are independent of baseline HbA1c 1, 2
• Do not reduce dose based on eGFR—use the standard 10 mg dose for cardiovascular/renal protection regardless of eGFR level (as long as ≥20 mL/min/1.73 m²) 2, 4
• Do not stop metformin when starting SGLT2 inhibitors—continue metformin as long as eGFR ≥30 mL/min/1.73 m² 1