Canagliflozin is a potent, selective, and reversible inhibitor of sodium-glucose co-transporter 2 (SGLT2), the primary transporter responsible for glucose reabsorption in the proximal convoluted tubule of the kidney. By inhibiting SGLT2, it reduces renal glucose reabsorption, increases urinary glucose excretion (UGE), and lowers plasma glucose levels in an insulin-independent manner. It is indicated for the management of type 2 diabetes mellitus (T2DM) in adults, often providing additional benefits of weight loss and modest blood pressure reduction.
Adult: The recommended starting dose is 100 mg orally once daily, taken before the first meal of the day. May be increased to 300 mg once daily in patients tolerating 100 mg who require additional glycemic control.
Note: Take orally, with or without food, but preferably before the first meal of the day. The tablet should be swallowed whole with a glass of water. Maintain adequate hydration to reduce the risk of volume depletion.
Canagliflozin inhibits the sodium-glucose co-transporter 2 (SGLT2) located in the S1 segment of the proximal renal tubule. SGLT2 is responsible for reabsorbing approximately 90% of the glucose filtered by the glomerulus. Inhibition of SGLT2 reduces the renal threshold for glucose (RTG) from ~180 mg/dL to ~70-90 mg/dL, leading to increased excretion of glucose in the urine (glycosuria). This results in a reduction of plasma glucose concentrations in an insulin-independent manner.
Pregnancy: Category C. Not recommended during the second and third trimesters due to potential risks to the fetus based on animal data (renal pelvic and tubule dilatation). Use only if the potential benefit justifies the potential risk to the fetus. Insulin is the preferred drug for glycemic control in pregnant women.
Driving: Patients should be cautioned about the potential for dizziness, lightheadedness, or syncope due to hypotension, especially during initiation. They should not drive or operate machinery if they experience these symptoms.
| Insulin or Insulin Secretagogues (Sulfonylureas, Meglitinides) | Increased risk of hypoglycemia. Dose reduction of insulin or secretagogue may be required. | Major |
| Diuretics (especially loop diuretics) | Additive risk of volume depletion, hypotension, and worsening of renal function. | Major |
| Digoxin | Canagliflozin may increase digoxin exposure (Cmax by 20%, AUC by 36%). Monitor digoxin levels. | Moderate |
| Rifampin | Decreases canagliflozin exposure (AUC by 51%). Consider increasing canagliflozin dose if used concomitantly. | Moderate |
| Phenytoin, Phenobarbital, Rifampin (UGT inducers) | May decrease canagliflozin efficacy. Monitor glycemic control. | Moderate |
| Lithium | The diuretic effect of canagliflozin may reduce lithium clearance, increasing the risk of lithium toxicity. Monitor lithium levels closely. | Major |