Invokana (canagliflozin) is the second authorised drug in the sodium glucose co transporter 2 (SGLT2) group for the treatment of type 2 diabetes in adults (1,2). The recommended starting dose is 100 mg once daily. If appropriate, the dose can be increased to 300 mg once daily, provided that the kidney function is normal.
Canagliflozin was shown to be more effective than placebo, and at least as effective as comparator drugs, at reducing the levels of HbA1c when used alone or in combination with other antidiabetic drugs. No clinically relevant differences in the total number of adverse events were found between canagliflozin and comparator drugs. It is unknown whether canagliflozin can prevent clinically relevant endpoints such as macro and micro vascular complications and death.
IRF finds that the rationale for combining metformin with other antidiabetic drugs is uncertain, since only metformin has a well-documented beneficial effect on cardiovascular risk (3). However, combination therapy may be relevant in patients with pronounced symptoms of hyperglycaemia, but in such cases canagliflozin may be less interesting, because the most frequent adverse events, including polyuria, thirst, dehydration, vulvovaginal candidiasis as well as balanitis or balanoposthitis, imitate the presenting symptoms of type 2 diabetes.
It is IRF’s overall assessment that canagliflozin is not first-line treatment for type 2 diabetes. In a choice between SGLT2 inhibitors and a sulphonylurea (SU) as add-on therapy to metformin, the significantly higher treatment price and lack of long-term data on relevant clinical endpoints and safety should be considered. SGLT2 inhibitors can be used as add-on to metformin in patients who despite careful dose titration experience hypoglycaemia during treatment with SU, but the DPP-4 inhibitors are probably preferable in this situation.
Invokana (canagliflozin) was marketed on 26 May 2014. General reimbursement is currently granted.