2 The technology

2.1 Canagliflozin (Invokana, Janssen-Cilag) is an orally administered selective sodium–glucose cotransporter‑2 (SGLT‑2) inhibitor. It lowers blood glucose in people with type 2 diabetes by blocking the reabsorption of glucose in the kidneys and promoting excretion of excess glucose in the urine.

2.2 Canagliflozin has a European marketing authorisation for treating type 2 diabetes in adults aged 18 years and older 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 'with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control'.

    The recommended starting dosage of canagliflozin is 100 mg once daily. In patients tolerating canagliflozin 100 mg once daily who have an estimated glomerular filtration rate (eGFR) of at least 60 ml/minute/1.73 m2 or creatinine clearance (CrCl) of at least 60 ml/minute and need tighter glycaemic control, the dosage can be increased to 300 mg once daily. For patients with renal impairment, the summary of product characteristics notes that canagliflozin should not be initiated in patients with an eGFR of less than 60 ml/minute/1.73m2 or CrCl of less than 60 ml/minute. In patients tolerating canagliflozin whose eGFR falls persistently below 60 ml/minute/1.73 m2 or whose CrCl persistently falls below 60 ml/minute, the dose of canagliflozin should be adjusted to or maintained at 100 mg once daily. Canagliflozin should be discontinued when eGFR is persistently below 45 ml/minute/1.73 m2 or CrCl is persistently below 45 ml/minute.

2.3 The summary of product characteristics states the following adverse reactions for canagliflozin as the most commonly reported: hypoglycaemia in combination with insulin or a sulfonylurea, vulvovaginal candidiasis, urinary tract infection, and polyuria or pollakiuria (that is, urinary frequency). For full details of adverse reactions and contraindications, see the summary of product characteristics.

2.4 According to the British national formulary (April 2014), the drug's price (excluding VAT) is £39.20 for canagliflozin 100 mg (30 tablets) and £49.99 for canagliflozin 300 mg (30 tablets). The expected annual cost of canagliflozin is £476.93 for the 100 mg daily dosage and £608.21 for the 300 mg daily dosage. Costs may vary in different settings because of negotiated procurement discounts.

  • National Institute for Health and Care Excellence (NICE)