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* Therapeutic indications:
Invokana is indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control as:
– Monotherapy:
When diet and exercise alone do not provide adequate glycaemic control in patients for whom the use of metformin is considered inappropriate due to intolerance or contraindications.
– Add-on therapy:
Add-on therapy with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control.
* Dosage and administration:
– Invokana should be taken orally once a day, preferably before the first meal of the day. Tablets should be swallowed whole.
– If a dose is missed, it should be taken as soon as the patient remembers; however, a double dose should not be taken on the same day.
– The recommended starting dose of canagliflozin is 100 mg once daily. In patients tolerating canagliflozin 100 mg once daily who have an eGFR >/= 60 mL/min/1.73 m2 or CrCl >/= 60 mL/min and need tighter glycaemic control, the dose can be increased to 300 mg once daily orally.
– Care should be taken when increasing the dose in patients >/= 75 years of age, patients with known cardiovascular disease, or other patients for whom the initial canagliflozin-induced diuresis poses a risk. In patients with evidence of volume depletion, correcting this condition prior to initiation of canagliflozin is recommended.
– When canagliflozin is used as add-on therapy with insulin or an insulin secretagogue (e.g., sulphonylurea), a lower dose of insulin or the insulin secretagogue may be considered to reduce the risk of hypoglycaemia.
* Pharmacotherapeutic group:
Drugs used in diabetes, other blood glucose lowering drugs, excluding insulins. ATC code: A10BX11
* Mechanism of action:
Sodium-glucose co-transporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Canagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose (RTG), and thereby increases urinary glucose excretion (UGE), lowering elevated plasma glucose concentrations by this insulin-independent mechanism in patients with type 2 diabetes. The increased UGE with SGLT2 inhibition also translates to an osmotic diuresis, with the diuretic effect leading to a reduction in systolic blood pressure; the increase in UGE results in a loss of calories and therefore a reduction in body weight, as has been demonstrated in studies of patients with type 2 diabetes.
Canagliflozin’s action to increase UGE directly lowering plasma glucose is independent of insulin. Improvement in homeostasis model assessment for beta-cell function (HOMA beta-cell) and improved beta-cell insulin secretion response to a mixed-meal challenge has been observed in clinical studies with canagliflozin.
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