Kidney Week

Abstract: TH-PO1147

Canagliflozin Reduces the Risk of Renal Events in People with Type 2 Diabetes Mellitus and Normoalbuminuria

Session Information

• Late-Breaking Clinical Trials Posters
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• No subcategory defined

Authors

• Perkovic, Vlado, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia

Vlado Perkovic,

• Neuen, Brendon Lange, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia

Brendon Lange Neuen,

• Ohkuma, Toshiaki, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia

Toshiaki Ohkuma,

• Matthews, David R., Oxford Centre for Diabetes, Endocrinology and Metabolism and Harris Manchester College, University of Oxford, Oxford, United Kingdom

David R. Matthews,

• de Zeeuw, Dick, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Dick de Zeeuw,

• Mahaffey, Kenneth W., Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States

Kenneth W. Mahaffey,

• Fulcher, Greg, Royal North Shore Hospital, Sydney, New South Wales, Australia

Greg Fulcher,

• Li, Qiang, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia

Qiang Li,

• Jardine, Meg J., The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia

Meg J. Jardine,

• Oh, Richard, Janssen Research & Development, LLC, Raritan, New Jersey, United States

Richard Oh,

• Lambers Heerspink, Hiddo Jan, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan Lambers Heerspink,

• Neal, Bruce, The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia

Bruce Neal,

Background

It has been postulated that the renoprotective effect of SGLT2 inhibitors is primarily due to restoration of tubuloglomerular feedback, which ameliorates glomerular hyperfiltration and lowers albuminuria. As a result, these agents might not be as effective in people with type 2 diabetes mellitus (T2DM) and normoalbuminuria (urinary albumin:creatinine ratio [UACR] <30 mg/g). Ongoing renal outcome studies are including participants who mostly or entirely have macroalbuminuria. We therefore sought to determine the renal effects of canagliflozin in people with normoalbuminuria in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program.

Methods

The CANVAS Program randomized people with T2DM and high risk of cardiovascular disease to canagliflozin or placebo. We included participants with normoalbuminuria in this analysis, and further divided them into tertiles according to baseline UACR (low, mid, or high normoalbuminuria), and into subgroups based on estimated glomerular filtration rate (eGFR; <45, 45-<60, 60-<90, and ≥90 mL/min/1.73m²). We analyzed the effects of canagliflozin on renal outcomes in people with normoalbuminuria overall and across these subgroups.

Results

Among 10,142 CANVAS participants, 7,007 (69%) had normoalbuminuria (mean age 63 years, BP 135/77 mmHg, HbA1c 8.2%, eGFR 78.3 mL/min/1.73m²). In this population, canagliflozin reduced average UACR by 9% (95% CI 7-12%) compared to placebo over 338 weeks. Mean annual change in eGFR for placebo and canagliflozin treated participants was –0.47 and +0.59 mL/min/1.73m², respectively (placebo-subtracted difference 1.06 mL/min/1.73m²). Canagliflozin reduced the risk of the composite renal outcome of 40% decrease in eGFR, end-stage kidney disease, or renal death by half (HR 0.50, 95% CI 0.33-0.77). The effect on the composite renal outcome appeared broadly consistent across UACR and eGFR subgroups (P heterogeneity = 0.16 and 0.10, respectively).

Conclusion

Canagliflozin reduces the risk of eGFR decline and renal outcomes in people with normoalbuminuria despite modest albuminuria reductions. Multiple mechanisms of renal benefit from SGLT2 inhibition might be important in T2DM.

Funding

• Commercial Support – Janssen Research & Development, LLC