Canagliflozin Therapy for Type 2 Diabetes

Mechanism and Benefits

• The American Diabetes Association recommends canagliflozin as a treatment option for type 2 diabetes, providing high glucose-lowering efficacy with minimal risk for hypoglycemia when used as monotherapy 1
• Canagliflozin is associated with weight loss and blood pressure reduction benefits, according to the American College of Cardiology 1

Major Safety Concerns

Amputation Risk

• The FDA has issued a Black Box Warning for canagliflozin, citing an increased risk for lower-limb amputation (6.3 vs. 3.4 per 1,000 patient-years with placebo; HR 1.97 [95% CI 1.41, 2.75]) 1

Fracture Risk

• The American College of Cardiology recommends using canagliflozin with caution in patients with a history of osteoporosis due to an increased fracture risk (15.4 vs. 11.9 participants with fracture per 1,000 patient-years; HR 1.26 [95% CI 1.04, 1.52]) 1, 2

Diabetic Ketoacidosis (DKA)

• The American College of Cardiology notes that canagliflozin may increase the risk of diabetic ketoacidosis, particularly in patients with insulin deficiency, reduced caloric intake, acute illness, surgical procedures, and alcohol consumption 3, 4
• Patients should be educated about symptoms of DKA (nausea, vomiting, abdominal pain, weakness) and instructed to seek urgent medical attention if these occur, as recommended by the American College of Cardiology 4

Dosing and Renal Considerations

• The American College of Cardiology recommends a starting dose of 100 mg orally once daily, with a maximum dose of 100 mg daily for patients with eGFR 30-59 mL/min/1.73 m² 5

Special Precautions

• The American College of Cardiology advises discontinuing canagliflozin at least 3 days before scheduled surgery to prevent postoperative ketoacidosis 5
• Canagliflozin may increase hypoglycemic potential when combined with insulin or sulfonylureas; the American College of Cardiology recommends considering reducing doses of these medications 4
• The American Heart Association notes that canagliflozin may increase LDL cholesterol levels 6

Patient Education and Monitoring

• The American College of Cardiology recommends educating patients about proper foot care and monitoring for signs of infection or injury, as well as instructing patients to monitor glucose more closely during the first 4 weeks of therapy 4
• Patients should be informed about the risk and symptoms of genital mycotic infections and appropriate management, according to the American College of Cardiology 4