What are the recommendations for using SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors in patients with type 2 diabetes?

SGLT2 Inhibitor Recommendations for Type 2 Diabetes

SGLT2 inhibitors should be used as first-line therapy in all patients with type 2 diabetes who have chronic kidney disease (eGFR ≥20 mL/min/1.73 m² with albuminuria ≥200 mg/g), established cardiovascular disease, or heart failure, regardless of baseline HbA1c levels or need for additional glucose lowering. 1, 2

Primary Indications (Use Regardless of Glycemic Control)

Chronic Kidney Disease

• Initiate SGLT2 inhibitors in all patients with eGFR ≥20 mL/min/1.73 m² and albuminuria ≥200 mg/g creatinine (A-level recommendation) 1, 3
• For patients with eGFR 20-60 mL/min/1.73 m² without albuminuria, SGLT2 inhibitors are still recommended by KDIGO 2022 guidelines to prevent CKD progression 1
• Once initiated, continue SGLT2 inhibitors even if eGFR falls below 20 mL/min/1.73 m², unless dialysis is started 3
• The renal protective effects persist independent of glucose-lowering at low eGFR 1, 3

Established Cardiovascular Disease

• All patients with type 2 diabetes and established atherosclerotic cardiovascular disease should receive an SGLT2 inhibitor to reduce major adverse cardiovascular events, cardiovascular death, and heart failure hospitalizations 1, 2
• Empagliflozin, canagliflozin, and dapagliflozin have all demonstrated significant reductions in cardiovascular events 1, 4

Heart Failure

• For patients with heart failure with reduced ejection fraction (EF <45%), SGLT2 inhibitors provide the greatest level of evidence for benefit and should be initiated regardless of diabetes status 2, 3
• For heart failure with preserved ejection fraction (EF >40%), SGLT2 inhibitors reduce heart failure hospitalizations (Class 2a recommendation) 3

Glycemic Control Indication

When Additional Glucose Lowering is Needed

• Starting dose: 10 mg once daily (empagliflozin) or 100 mg once daily (canagliflozin), taken in the morning with or without food 5, 6
• May increase to 25 mg once daily (empagliflozin) or 300 mg once daily (canagliflozin) in patients tolerating the lower dose who have eGFR ≥60 mL/min/1.73 m² and require additional glycemic control 5, 6
• Expected HbA1c reduction: 0.6-0.8% (6-8 mmol/mol) 4
• The glucose-lowering effect diminishes when eGFR <45 mL/min/1.73 m², but cardiovascular and renal benefits persist 3

eGFR-Based Initiation and Continuation Algorithm

Initiation:

• Do NOT initiate if eGFR <45 mL/min/1.73 m² for glycemic control alone 5
• DO initiate if eGFR ≥20 mL/min/1.73 m² when indication is CKD with albuminuria, cardiovascular disease, or heart failure 1, 3
• Canagliflozin can be started down to eGFR 30 mL/min/1.73 m² 1

Continuation:

• Discontinue empagliflozin if eGFR falls persistently below 45 mL/min/1.73 m² when used solely for glycemic control 5
• Continue SGLT2 inhibitors for cardiorenal protection even when eGFR falls below initiation threshold, unless dialysis is required 3

Patient Selection: Who Should NOT Receive SGLT2 Inhibitors Initially

Do NOT initiate in patients with:

• Normal albumin/creatinine ratio (<30 mg/g) AND no evidence of CKD AND no cardiovascular disease AND no heart failure (Grade A recommendation) 3
• Severe renal impairment (eGFR <20 mL/min/1.73 m²), end-stage renal disease, or dialysis 5
• History of serious hypersensitivity reaction to the specific SGLT2 inhibitor 5, 6

Use with caution in:

• Patients with active foot ulcers or high amputation risk (particularly with canagliflozin) - requires careful shared decision-making 2, 6
• Patients at risk for volume depletion (elderly, on loop diuretics, low systolic blood pressure) - assess and correct volume status before initiating 5, 6

Critical Safety Monitoring

Before Initiation

• Assess renal function (eGFR and albuminuria) 5, 6
• Assess volume status and correct volume depletion, especially in elderly patients, those with renal impairment, or those on diuretics 5, 6

During Treatment

• Counsel patients about genital yeast infections (6% vs 1% placebo) and proper genital hygiene 3
• Monitor for signs of diabetic ketoacidosis, particularly in patients with type 1 diabetes or those with prolonged fasting, surgery, or acute illness 5, 6
• Withhold SGLT2 inhibitors at least 3 days prior to surgery or procedures with prolonged fasting 6
• Evaluate promptly for urinary tract infections (urosepsis, pyelonephritis) if symptoms develop 5, 6

Hypoglycemia Risk

• When initiating SGLT2 inhibitors in patients on insulin or insulin secretagogues, reduce the dose of these agents to minimize hypoglycemia risk 5, 6
• SGLT2 inhibitors alone do not cause hypoglycemia 4

Combination Therapy

• SGLT2 inhibitors can be used concomitantly with RAS inhibitors and mineralocorticoid receptor antagonists like finerenone 3
• If additional glucose lowering is needed beyond SGLT2 inhibitors, GLP-1 receptor agonists are generally the preferred add-on therapy 1
• For patients who cannot tolerate SGLT2 inhibitors, GLP-1 receptor agonists with proven cardiovascular benefits (liraglutide, semaglutide, dulaglutide) are appropriate alternatives 1

Monitoring Schedule

• Annual screening for albuminuria and eGFR in patients with normal kidney function 3
• Reassess SGLT2 inhibitor indication if albuminuria develops (≥30 mg/g), eGFR declines (<60 mL/min/1.73 m²), or cardiovascular disease/heart failure develops 3
• Monitor renal function during therapy, particularly after initiation 5