Canagliflozin for the Treatment of Diabetic Kidney Disease and Implications for Clinical Practice: A Narrative Review

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Canagliflozin for the Treatment of Diabetic Kidney Disease and Implications for Clinical Practice: A Narrative Review Davida Kruger . Virginia Valentine

Received: March 12, 2020 Ó The Author(s) 2020

ABSTRACT Type 2 diabetes mellitus (T2DM) affects millions of people worldwide, elevating their risk of developing a range of complications, including chronic kidney disease (CKD). People with T2DM and CKD (i.e., diabetic kidney disease, DKD) have an increased risk of progressing to end-stage kidney disease (ESKD), experiencing cardiovascular complications, and premature death. Despite this, DKD is primarily addressed through management of risk factors, and there are few pharmaceutical treatments capable of reversing or delaying disease progression. Canagliflozin is a sodium glucose co-transporter 2 inhibitor that was initially developed as

Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/m9.figshare. 12164172. D. Kruger (&) Henry Ford Health System, Detroit, MI, USA e-mail: [email protected] V. Valentine Clinica La Esperanza, Albuquerque, NM, USA

a blood glucose–lowering agent for people with T2DM. Evidence from clinical trials of canagliflozin in people with T2DM, as well as evidence from cardiovascular outcomes trials in people with T2DM and high cardiovascular risk, provided preliminary evidence suggesting that it may also have beneficial renal effects. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial was a dedicated renal outcomes trial of canagliflozin that assessed its renal effects in people with DKD. Overall, the CREDENCE trial demonstrated that canagliflozin improves renal outcomes and slows early disease progression in people with DKD. These data supported the approval of canagliflozin for the treatment DKD, the first new treatment in almost 20 years; therefore, it is important for clinicians to understand how to implement this treatment in their clinical practice.

Keywords: Canagliflozin; Cardiovascular disease; Diabetic kidney disease; Randomized trials; Sodium glucose co-transporter 2 inhibitor; Type 2 diabetes

Diabetes Ther

Key Summary Points People with type 2 diabetes have a high risk of developing diabetic kidney disease (DKD), which is the leading cause of endstage kidney disease There are few pharmaceutical treatments capable of reversing or delaying the progression of DKD The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial was a dedicated renal outcomes trial of the sodium glucose co-transporter 2 inhibitor canagliflozin in people with DKD Results from CREDENCE demonstrated that canagliflozin improves renal outcomes and slows early disease progression in people with DKD This article reviews the key results from CREDENCE, along with context and guidance for clinicians on how to implement canagliflozin treatment in their clinical practice

DIABETIC KIDNEY DISEASE: BURDEN AND TREATMENT More than 34 million Americans