Canagliflozin Use and Dosing in Type 2 Diabetes
The recommended dosing of canagliflozin for patients with type 2 diabetes is 100 mg orally once daily, taken before the first meal of the day, with potential dose escalation to 300 mg daily in patients with eGFR ≥60 mL/min/1.73 m² who require additional glycemic control. 1
Indications and Benefits
Canagliflozin is indicated for:
- Improving glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes as an adjunct to diet and exercise 1
- Reducing risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes and established cardiovascular disease 1
- Reducing risk of end-stage kidney disease, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in patients with type 2 diabetes and diabetic nephropathy with albuminuria 1, 2
The CREDENCE trial demonstrated that canagliflozin 100 mg daily reduced the risk of kidney failure and cardiovascular events by 30% compared to placebo in patients with type 2 diabetes and kidney disease 2.
Dosing Guidelines
- Starting dose: 100 mg orally once daily, taken before the first meal of the day 1
- Dose escalation: May increase to 300 mg once daily in patients with eGFR ≥60 mL/min/1.73 m² who need additional glycemic control 1
- For cardiovascular and renal protection: 100 mg orally once daily is the recommended dose 3, 1
Renal Dosing Adjustments
- eGFR 30-59 mL/min/1.73 m²: Maximum dose 100 mg daily 3, 1
- eGFR <30 mL/min/1.73 m²: Not recommended for glycemic control 1
- For patients with diabetic nephropathy with albuminuria: Can be used down to eGFR 30 mL/min/1.73 m² specifically for renal protection 3
Patient Selection Considerations
Canagliflozin is particularly beneficial for patients with:
- Type 2 diabetes with established cardiovascular disease 3
- Type 2 diabetes with heart failure 3
- Type 2 diabetes with diabetic kidney disease and albuminuria (UACR >300 mg/g) 3
Precautions and Monitoring
- Before initiation: Assess renal function and volume status; correct volume depletion before starting 1
- Surgery preparation: Withhold canagliflozin at least 3 days before planned surgery with prolonged fasting 1
- Hypoglycemia risk: Consider reducing doses of insulin or insulin secretagogues when adding canagliflozin 3
- Volume depletion: Monitor for signs of dehydration, especially in elderly patients or those on diuretics 3, 1
Common Adverse Effects
Special Considerations
- Cardiovascular benefits: The CANVAS trial showed reduction in MACE in patients with established cardiovascular disease 3
- Renal benefits: The CREDENCE trial demonstrated significant reduction in renal outcomes and progression to end-stage kidney disease 2
- Weight effects: Canagliflozin produces modest weight reduction (0.73-1.19 kg over 28 days in clinical studies) 5
- Postprandial glucose: Canagliflozin 300 mg reduces postprandial glucose excursions through both renal and non-renal mechanisms 6
Contraindications
Clinical Pearls
- When initiating canagliflozin in patients with well-controlled HbA1c or history of frequent hypoglycemia, consider reducing sulfonylurea dose or reducing total daily insulin dose by approximately 20% 3
- Educate patients about potential genital mycotic infections and the importance of genital hygiene 3
- Instruct patients to monitor for symptoms of diabetic ketoacidosis (nausea, vomiting, abdominal pain, weakness), which can occur even with blood glucose in the 150-250 mg/dL range 3
- Use with caution in patients with prior amputation, severe peripheral neuropathy, or diabetic foot ulcers 3
Canagliflozin offers a unique mechanism of action independent of insulin secretion and action, making it a valuable addition to the therapeutic options for type 2 diabetes management, particularly as add-on therapy for patients requiring additional glycemic control or those with cardiovascular or renal comorbidities 4.