The SGLT2 inhibitor Canagliflozin ( Invokana ) .... as an adjunct to the standard of care in adults with type 2 diabetes mellitus ( T2DM ) and stage 2 or stage 3 chronic kidney disease ( CKD ) and albuminuria.
The application is based on data from the phase III CREDENCE study, which has evaluated the efficacy and safety of Canagliflozin versus placebo in this high-risk patient population when used in addition to the current standard of care.
Approximately 40% of T2DM patients develop diabetic kidney disease. This has a major impact on their physical and emotional health as well as their quality of life, and amplifies their risk of additional diabetes complications such as cardiovascular disease, infections, fatigue, depression, adverse drug reactions and premature death.
Data from the Swiss dialysis registry have shown that around one third of dialysis patients have type 2 diabetes mellitus and that approximately 17% of patients have diabetic nephropathy as an underlying kidney disease.
There is therefore a great need for new therapies that cater for the kidney-related complications of type 2 diabetes mellitus.
In European Union, Canagliflozin is currently indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise.
The initiation dose is 100mg once daily in adults with an eGFR of greater than or equal to 60 mL/min/1.73 m2 and can be increased to 300mg once daily orally if tighter glycaemic control is needed.
Canagliflozin should not be initiated if eGFR is less than 60 mL/min/1.73 m2.
In patients tolerating Canagliflozin whose eGFR falls persistently below 60 mL/min/1.73 m2 the dose should be adjusted to or maintained at 100mg once daily.
Canagliflozin should be stopped if eGFR falls persistently below 45 mL/min/1.73 m2.
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 mellitus.
The CREDENCE ( Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation ) study was the first dedicated and fully recruited renal outcome trial evaluating renal and cardiovascular outcomes in people with type 2 diabetes mellitus and chronic kidney disease with a SGLT2 inhibitor.
It was a phase III randomised, double-blind, event-driven, placebo-controlled, parallel-group, two-arm multicentre study of the effects of Canagliflozin on renal and cardiovascular outcomes in subjects with type 2 diabetes mellitus and chronic kidney disease.
In particular, it compared the efficacy and safety of Canagliflozin versus placebo in preventing clinically important kidney and cardiovascular outcomes in patients with type 2 diabetes mellitus and CKD when used in addition to standard of care, including a maximum tolerated daily dose of an angiotensin-converting enzyme inhibitor ( ACEi ) or angiotensin receptor blocker ( ARB ).
The study was stopped early in July 2018 owing to positive efficacy findings.
Source: Swissmedic, 2019