Invokana: new SGLT2 inhibitor for type II diabetes

Janssen-Cilag has launched Invokana (canagliflozin) for the treatment of type II diabetes inadequately controlled with diet and exercise.

Invokana (canagliflozin) is given once daily at a starting dose of 100mg, increasing if necessary to 300mg once daily in patients with CrCl ≥60ml/min
Invokana (canagliflozin) is given once daily at a starting dose of 100mg, increasing if necessary to 300mg once daily in patients with CrCl ≥60ml/min

Invokana can be used as monotherapy when treatment with metformin is inappropriate, or in combination with other hypoglycaemics, including insulin, when these alone are inadequate.

PHARMACOLOGY

Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor which lowers blood glucose levels by reducing renal glucose reabsorption and increasing urinary glucose excretion, independently of insulin.1

CLINICAL STUDIES

In a 26-week in 584 patients with type II diabetes, a significant reduction in HbA1c was observed in both the 100mg and 300mg canagliflozin groups compared with placebo (-0.77%, -1.03% and 0.14% respectively; p<0.001 for both). Significant reductions in fasting plasma glucose, two-hour postprandial glucose, body weight and systolic BP compared with placebo were also observed (p<0.001 for all).2

Dual therapy versus glimepiride

In the study in 1,450 patients with type II diabetes inadequately controlled by metformin alone, add-on therapy with canagliflozin 100mg daily was non-inferior to glimepiride (titrated to maximum effect) for lowering HbA1c (least squares mean difference -0.01% [95% CI -0.11 to 0.09]) and canagliflozin 300mg was statistically superior to glimepiride -0.12% [-0.22 to -0.02]).3 In a 52-week extension to this study, reductions in HbA1c levels, fasting plasma glucose, body weight and systolic BP in both canagliflozin groups were sustained at 104 weeks.4

Dual therapy versus sitagliptin

In another study involving 1,284 patients inadequately controlled by metformin alone, canagliflozin 300mg daily was superior to, and the 100mg dose non-inferior to, sitagliptin 100mg daily in terms of HbA1c reduction at week 52 (upper limit of 95% CI <0.0% and <0.3%, respectively).4

Triple therapy versus sitagliptin

In the trial (n=755), canagliflozin 300mg used as triple therapy with metformin plus sulfonylurea demonstrated superiority to sitagliptin in reducing HbA1c, with a least squares mean difference of – 0.37% (95% CI –0.50 to –0.25).5

Side-effect profile

The most commonly reported adverse effects of canagliflozin were hypoglycaemia in combination with insulin or a sulfonylurea, vulvovaginal candidiasis, urinary tract infection, and polyuria or pollakiuria.1

References:

View Invokana drug record

Further information: Janssen-Cilag

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