2 The technologies

2.1 Canagliflozin (Invokana, Janssen), dapagliflozin (Forxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim and Lilly UK) are all selective sodium‑glucose cotransporter 2 (SGLT‑2) inhibitors, which block the reabsorption of glucose in the kidneys and promote excretion of excess glucose in the urine. Through this mechanism these drugs may help control glycaemia independently of insulin pathways. They all have UK marketing authorisations for treating type 2 diabetes to improve glycaemic control in adults:

  • as monotherapy: when diet and exercise alone do not provide adequate glycaemic control in people for whom the use of metformin is considered inappropriate due to intolerance or contraindications

  • as add‑on combination therapy: with other glucose–lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control.

Canagliflozin

2.2 The recommended starting dosage of canagliflozin is 100 mg orally once daily. In people 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 of at least 60 ml/minute and who need tighter glycaemic control, the dose can be increased to 300 mg once daily. For people with renal impairment, the summary of product characteristics notes that canagliflozin should not be started in people with an eGFR of less than 60 ml/minute/1.73 m2 or creatinine clearance of less than 60 ml/minute. In people tolerating canagliflozin whose eGFR persistently falls below 60 ml/minute/1.73 m2 or whose creatinine clearance 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 creatinine clearance is persistently below 45 ml/minute.

2.3 The summary of product characteristics lists the following adverse reactions for canagliflozin as the most commonly reported: balanitis, constipation, dyslipidaemia, haematocrit increase, nausea, polyuria, thirst, urinary tract infection and vulvovaginal candidiasis. For full details of adverse reactions and contraindications, see the summary of product characteristics.

2.4 The price of canagliflozin is £39.20 for a 30‑tablet pack of 100 mg or 300 mg tablets (excluding VAT; 'British national formulary' [BNF], accessed online September 2015). Costs may vary in different settings because of negotiated procurement discounts.

Dapagliflozin

2.5 The recommended dosage is 10 mg dapagliflozin orally once daily for monotherapy and add‑on combination therapy with other glucose‑lowering medicinal products including insulin.

2.6 The summary of product characteristics lists the following adverse reactions for dapagliflozin: back pain, balanitis, creatinine renal clearance decrease, dizziness, dysuria, dyslipidaemia, elevated haematocrit, polyuria, urinary tract infection and vulvovaginitis. Dapagliflozin is not recommended for people with moderate to severe renal impairment (people with a creatinine clearance rate of less than 60 ml/min or an eGFR of less than 60 ml/min/1.73 m2). For full details of adverse reactions and contraindications, see the summary of product characteristics.

2.7 The list price of dapagliflozin is £36.59 for a 28‑tablet pack of 5 mg or 10 mg tablets (excluding VAT; 'British national formulary' [BNF], accessed online September 2015). Costs may vary in different settings because of negotiated procurement discounts.

Empagliflozin

2.8 The recommended starting dosage is 10 mg orally once daily for monotherapy. According to the summary of product characteristics, the dose can be increased to a maximum of 25 mg daily for people who tolerate empagliflozin well and need tighter glycaemic control, if they have an eGFR of 60 ml/min/1.73 m2 or more.

2.9 The summary of product characteristics includes the following adverse reactions for empagliflozin: balanitis, increased urination, pruritus, urinary tract infection, vaginal moniliasis and vulvovaginitis. For full details of adverse reactions and contraindications, see the summary of product characteristics.

2.10 The list price of empagliflozin is £36.59 for a 28‑tablet pack of 10 mg or 25 mg tablets (excluding VAT; 'British national formulary' [BNF], accessed online September 2015). Costs may vary in different settings because of negotiated procurement discounts.

  • National Institute for Health and Care Excellence (NICE)