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July 2020

New treatment for diabetic kidney disease





The first new treatment to slow the progression of kidney disease in 20 years has been approved in Europe. The SGLT2 inhibitor canagliflozin (Invokana) can now be prescribed for patients with type 2 diabetes to treat diabetic kidney disease (DKD).

Previously, the only options known to reduce progression of kidney disease were ACE inhibitors and angiotensin receptor blockers (ARBs).

Under the license extension, the 100mg daily dose of canagliflozin is indicated as an add-on to standard care with ACE inhibitors or ARBs.

Canagliflozin is the first SGLT2 inhibitor that can be initiated in patients with type 2 diabetes (T2D) with an estimated glomerular filtration rate (eGFR) of ≥45 to <60 ml/min/1.73m2. Up until now, it was only indicated for patients with an eGFR >60.

In addition, T2D patients with albuminuria (urinary albumin: creatinine ratio >30 mg/mmol) and an eGFR ≥30 can now be initiated on canagliflozin 100 mg and also maintained on treatment until dialysis or renal transplantation

The European Commission (EC) has approved the license extension based on important renal outcome data from the landmark Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial,1 which was the first dedicated renal outcomes trial in patients with DKD and T2D.

Lead study author Professor Vlado Perkovic, Professorial Fellow at the George Institute, Australia, Dean of Medicine at UNSW Sydney commented: ‘Canagliflozin is the first medical breakthrough in nearly 20 years proven to slow the progression of chronic kidney disease in patients with diabetes at high risk of developing kidney failure.

‘These impressive results from the CREDENCE study have significant clinical implications for preventing kidney failure and have now been incorporated in major kidney, diabetes and cardiovascular guidelines globally. They provide an opportunity to significantly improve the health of millions of people living with DKD.’

People with diabetes are five times more likely to need dialysis or a kidney transplant than those without. In the UK, diabetes is the leading cause of kidney failure, affecting 10,350 people with diabetes. Therefore, slowing the rate of progression of DKD is critical to the successful management of T2D and its known co-morbidities.

CREDENCE RESULTS

The CREDENCE trial is the first dedicated renal outcomes study in patients with DKD and T2DM. The study enrolled 4,401 subjects with an eGFR of 30 to <90mL/min/1.73m2 and albuminuria (urinary albumin: creatinine ratio >300 to 5000 mg/g).1 Importantly, all patients were treated on a background of standard of care for DKD (maximum tolerated dose of an  ACE inhibitor or ARB. Compared with placebo), canagliflozin demonstrated a 30% reduction in the risk of the primary composite endpoint, comprising end-stage renal disease, doubling of serum creatinine and renal or cardiovascular death.1

Rates of 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 or bone fractures. There was a small increased risk of diabetic ketoacidosis in the canagliflozin group. The study was stopped early in July 2018 because the efficacy findings were so positive.1 

INDICATION

Canagliflozin has been approved in the UK since November 2013. The recommended starting dose for T2DM is 100 mg once-daily. In patients tolerating this dose and with an eGFR ≥60 ml/ min/1.73m2 needing tighter glycaemic control, the dose can be increased to 300 mg once daily. In patients tolerating canagliflozin whose eGFR falls persistently below 60 ml/min/1.73m2, 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/min/1.73m2. For the treatment of DKD as an add-on to standard of care (e.g. ACEinhibitors or ARBs), a dose of 100 mg canagliflozin once daily should be used. In patients with severely increased albuminuria (urinary albumin: creatinine ratio >30 mg/mmol) canagliflozin can be initiated if eGFR ≥30 ml/min/1.73 m2 and used until renal replacement therapy or transplantation.2


1. Perkovic, V. et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019; 380:2295–2306.

2. EMC. SmPC. Invokana 100 mg and 300 mg film-coated tablets. Available at: https://www.medicines.org.uk/emc/product/8855/smpc.