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Invokana indication to reflect improved renal outcomes in patients with diabetic kidney disease and type 2 diabetes seen in CREDENCE study - European Commission has approved extended

The European Commission ( EC ) has approved the extension of the indication of Invokana ( Canagliflozin ) to include important renal outcome data from the landmark Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation ( CREDENCE ) trial.
Invokana is now the only sodium glucose co-transporter 2 inhibitor ( SGLT2i ) approved in Europe with an extended indication to treat diabetic kidney disease ( DKD ) in type 2 diabetes ( T2DM ) patients.

For the first time in Europe, T2DM patients with an estimated glomerular filtration rate ( eGFR ) between 60 and 45 mL/min/1.73m2 can now initiate treatment with Canagliflozin 100mg.
In addition, T2DM patients with albuminuria and an eGFR greater than or equal to 30 mL/min/1.73m2 can now start treatment with Canagliflozin 100mg and continue until dialysis or renal transplantation.

The CREDENCE trial is the first dedicated renal outcomes study in patients with diabetic kidney disease and type 2 diabetes. The study enrolled 4401 subjects with an eGFR of 30 to less than 90ml/min/1.73m2 and albuminuria ( urinary albumin: creatinine ratio more than 300 to 5000 mg/g ).
Importantly, all patients were treated on a background of standard of care for diabetic kidney disease, including a maximum tolerated dose of an ACE inhibitor or angiotensin receptor blocker ( ARB; sartan ).
The results has shown that Canagliflozin has demonstrated a 30% reduction, compared to placebo, in the risk of the primary composite endpoint, comprising end-stage renal disease ( ESRD ), doubling of serum creatinine and renal or cardiovascular ( CV ) death, with event rates of 43.2 vs 61.2 per 1000 patient years, respectively ( hazard ratio [ HR ]: 0.70; 95% Confidence Interval [ CI ]: 0.57 to 0.84; p less than 0.0001 ).

Rates of adverse events and serious adverse events were similar overall in the Canagliflozin group and the placebo group. There were no statistical differences in the incidence of lower limb amputations ( Canagliflozin 12.3 vs placebo 11.2 events per 1000 patient years; HR: 1.11; 95% CI: 0.79 to 1.56 ) or adjudicated bone fractures ( Canagliflozin 11.8 vs 12.1 events per 1000 patient years; HR: 0.98; 95% CI: 0.70 to 1.37 ).
The study was stopped early in July 2018, owing to positive efficacy findings.

Canagliflozin is an oral, once-daily medication that belongs to a class of medications called sodium glucose co-transporter 2 ( SGLT2 ) inhibitors.
SGLT2 inhibitors work by inhibiting SGLT2 co-transporter, which promotes the excretion of glucose via the urine, and thus helps lowering blood glucose levels in adults with type 2 diabetes.

Canagliflozin was approved in the European Union by the European Commission in November 2013. It is indicated for the treatment of adults with insufficiently controlled type 2 diabetes as an adjunct to diet and exercise, as monotherapy when Metformin is considered inappropriate due to intolerance or contraindications and in addition to other medicinal products for the treatment of diabetes.

The recommended initiation dose of Canagliflozin is 100 mg once daily in adults with an eGFR of greater than or equal to 60 mL/min/1.73 m2 and can be increased to 300 mg once daily if tighter glycaemic control is needed.
For patients with an eGFR of 45 to less than 60 mL/min/1.73 m2 the initiation dose is limited to 100mg once daily, if further glycaemic control is needed the addition of other anti-hyperglycaemic agents should be considered.
In patients with an eGFR of 30 to less than 45 mL/min/1.73 m2 with a urinary albumin/creatinine ratio more than 300 mg/g, the initiation dose is limited to 100 mg once daily, if further glycaemic control is needed the addition of other anti-hyperglycaemic agents should be considered.
Canagliflozin should not be initiated if eGFR is below 30 mL/min/1.73 m2, but for patients already taking Canagliflozin it should be continued at 100 mg until dialysis or renal transplantation is required.

An estimated 59 million adults in Europe have diabetes, around 90% of whom have type 2 diabetes mellitus. Approximately 40% of people with type 2 diabetes mellitus will go on to develop kidney disease. ( Xagena )

Source: Mundipharma, 2020