Kidney Week

Abstract: TH-PO185

Iron Biomarkers and Effects of Canagliflozin in Patients with Type 2 Diabetes and CKD: A Post Hoc Analysis of the CREDENCE Trial

Session Information

• Diabetic Kidney Disease: Clinical - I
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Koshino, Akihiko, University Medical Center Groningen, Groningen, Netherlands

Akihiko Koshino,

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

Brendon Lange Neuen,

• Arnott, Clare Gabrielle, The George Institute for Global Health, Newtown, New South Wales, Australia

Clare Gabrielle Arnott,

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

Bruce Neal,

• Jardine, Meg, The George Institute for Global Health, Newtown, New South Wales, Australia

Meg Jardine,

• Badve, Sunil, The George Institute for Global Health, Newtown, New South Wales, Australia

Sunil Badve,

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

Kenneth W. Mahaffey,

• Pollock, Carol A., Kolling Institute of Medical Research, St Leonards, New South Wales, Australia

Carol A. Pollock,

• Hansen, Michael K., Janssen Research and Development LLC, Spring House, Pennsylvania, United States

Michael K. Hansen,

• Wada, Takashi, Kanazawa University, Kanazawa, Ishikawa, Japan

Takashi Wada,

• Heerspink, Hiddo Jan L., University Medical Center Groningen, Groningen, Netherlands

Hiddo Jan L. Heerspink,

Background

Disturbed iron homeostasis occurs commonly in patients with chronic kidney disease (CKD) and is implicated in the development of anemia and adverse clinical events. This study aimed to determine the effects of canagliflozin on iron parameters in the CREDENCE trial and to assess whether the effects of canagliflozin on anemia and clinical outcomes were modified by iron deficiency (ID).

Methods

Patients with type 2 diabetes (T2D) and CKD were randomized to canagliflozin 100mg or placebo. We measured serum iron, total iron binding capacity (TIBC), transferrin saturation (TSAT) and ferritin at baseline and year 1. The effects of canagliflozin, relative to placebo, on iron markers were assessed with analysis of covariance. Interactions between baseline ID, defined as TSAT<20%, and the effects of canagliflozin on hemoglobin and clinical outcomes were evaluated with mixed effect models and Cox regression models, respectively.

Results

2414/4401 (54.9%) participants had available serum samples. Canagliflozin, compared to placebo, increased TIBC by 2.1% (95% CI 0.4, 3.8; p=0.01) and decreased ferritin by 11.3% (95% CI 3.1, 15.4; p<0.001) with no clear effect on iron and TSAT (Figure). At baseline, 924 (38.3%) participants had ID. Canagliflozin increased hemoglobin over time by 7.3 g/L (95% CI 6.2, 8.5; p<0.001) and 6.7 g/L (95% CI 5.2, 8.2; p<0.001) in patients with and without ID, respectively (p-interaction=0.38). Canagliflozin reduced CKD progression (HR 0.70, 95% CI 0.56-0.87) regardless of ID (p-interaction=0.83).

Conclusion

One-year treatment with canagliflozin increased TIBC and decreased ferritin in patients with T2D and CKD, suggesting improvement in iron use.

Funding

• Commercial Support – Janssen Research and Development