What is the recommended dosing and management plan for patients starting Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors?

SGLT2 Inhibitor Dosing and Management

Start empagliflozin 10 mg once daily, canagliflozin 100 mg once daily, or dapagliflozin 10 mg once daily in the morning—no dose titration is needed for cardiovascular or renal protection, as the lowest doses provide full cardioprotective benefit. 1

Initial Dosing by Agent

Empagliflozin

• Start at 10 mg orally once daily in the morning, with or without food 2
• May increase to 25 mg once daily if additional glycemic control is needed, but this provides no additional cardiovascular benefit 3, 1
• Do not initiate if eGFR is below 45 mL/min/1.73 m² 2

Canagliflozin

• Start at 100 mg orally once daily before the first meal of the day 4
• May increase to 300 mg once daily only in patients tolerating 100 mg who have eGFR ≥60 mL/min/1.73 m² and require additional glycemic control 4
• For cardiovascular or renal indications, maintain 100 mg dose 1

Dapagliflozin

• For glycemic control: Start at 5 mg once daily, may increase to 10 mg if needed 5, 6
• For heart failure, CKD, or cardiovascular risk reduction: Use fixed 10 mg once daily with no titration 5, 6

Pre-Initiation Assessment

Before starting any SGLT2 inhibitor, you must assess three critical parameters: 3

1. Renal function (eGFR) - Check baseline kidney function 3, 6, 2
2. Volume status - Assess for dehydration or hypovolemia 3, 6, 2
3. Current medications - Identify drugs requiring dose adjustment 3

Volume Status Management

• Correct volume depletion before initiating SGLT2 inhibitors 6, 2
• Reduce thiazide or loop diuretic dose by 50% in patients on high-dose diuretics to prevent symptomatic hypotension 3, 1
• Use particular caution in elderly patients, those with low systolic blood pressure, or those on diuretics 6, 2

Concomitant Medication Adjustments

Insulin Dose Reduction

If A1C is well-controlled at baseline or patient has history of frequent hypoglycemia, reduce basal insulin dose by 20% when starting SGLT2 inhibitor 3

Sulfonylurea Dose Reduction

Reduce sulfonylurea dose by 50% when initiating SGLT2 inhibitor in patients meeting glycemic targets or with hypoglycemia history 3

DPP-4 Inhibitors

No specific dose adjustment required, though combination is generally unnecessary 3

Renal Function Thresholds

Empagliflozin

• Do not initiate if eGFR <45 mL/min/1.73 m² 2
• Discontinue if eGFR falls persistently below 45 mL/min/1.73 m² 2

Canagliflozin and Dapagliflozin

• Can be initiated down to eGFR 30 mL/min/1.73 m² for cardiovascular and renal protection 1
• Dapagliflozin can be initiated down to eGFR 25 mL/min/1.73 m² for heart failure or CKD indications 5, 6

Continuation at Lower eGFR

Once initiated, SGLT2 inhibitors can be continued even if eGFR falls below initiation threshold, unless not tolerated or dialysis is started 3, 5

The 2022 KDIGO guideline recommends SGLT2 inhibitors for all patients with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m² independent of albuminuria 3, while the 2022 ADA recommends them for eGFR <60 mL/min/1.73 m² or albuminuria ≥200 mg/g 3

Patient Education and Monitoring

Critical Safety Counseling

Educate all patients on these four key risks before starting: 3

1. Genital mycotic infections - Proper genital hygiene is essential 3, 6, 2
2. Euglycemic diabetic ketoacidosis - Can occur even with blood glucose 150-250 mg/dL 3
3. Volume depletion symptoms - Light-headedness, orthostasis, weakness 3
4. Foot care - Particularly important with canagliflozin due to amputation risk 3

Home Glucose Monitoring

Instruct patients to monitor glucose more closely for the first 4 weeks of therapy 3

Ketoacidosis Warning Signs

Educate patients that if they experience nausea, vomiting, or weakness, they should seek medical attention immediately, as diabetic ketoacidosis can occur even with near-normal glucose readings 3

Temporary Discontinuation

Withhold SGLT2 inhibitors at least 3 days before major surgery or procedures with prolonged fasting to prevent postoperative ketoacidosis 5, 6, 4

Withhold during acute illness, prolonged fasting, or critical medical illness when patients are at greater risk for ketosis 3

Follow-Up Monitoring

Renal Function

• Monitor eGFR at baseline and as clinically indicated 6, 2
• A reversible decrease in eGFR with commencement is expected and generally not an indication to discontinue 3
• Increase monitoring frequency when eGFR <60 mL/min/1.73 m² 3

Foot Examinations

Follow-up foot pulse examination is particularly important with canagliflozin due to increased amputation risk in patients with prior amputation, severe peripheral arterial disease, neuropathy, or diabetic foot ulcers 3

Contraindications and Cautions

Absolute Contraindications

• History of serious hypersensitivity reaction to the specific SGLT2 inhibitor 6, 2
• Severe renal impairment, end-stage renal disease, or dialysis (for empagliflozin) 2

Avoid Canagliflozin If:

• History of prior amputation 3
• Severe peripheral arterial disease 3
• Neuropathy or diabetic foot ulcers 3
• History of osteoporosis 3

Use Caution If:

• History of recurrent genital candidiasis 3
• History of diabetic ketoacidosis 3
• History of pancreatitis (more relevant for GLP-1 RAs) 3