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Abstract: SA-PO261

Effect of Canagliflozin on Markers of Hepatic Steatosis and Fibrosis in Patients With Type 2 Diabetes and CKD

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Koshino, Akihiko, Rijksuniversiteit Groningen, Groningen, Groningen, Netherlands
  • Oshima, Megumi, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan
  • Arnott, Clare Gabrielle, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Fletcher, Robert A., The George Institute for Global Health, Newtown, New South Wales, Australia
  • Perkovic, Vlado, The George Institute for Global Health, Newtown, New South Wales, Australia
  • L Heerspink, Hiddo Jan, Rijksuniversiteit Groningen, Groningen, Groningen, Netherlands
  • Neuen, Brendon Lange, The George Institute for Global Health, Newtown, New South Wales, Australia
Background

Few treatments are available for nonalcoholic fatty liver disease (NAFLD), which occurs commonly in people with diabetes and chronic kidney disease (CKD) and is associated with adverse outcomes. This post-hoc analysis of the CREDENCE trial evaluated the effects of canagliflozin (Cana) on NAFLD risk scores in patients with diabetes and CKD, as well as their association with clinical outcomes.

Methods

Hepatic steatosis index, NAFLD fibrosis score and fibrosis-4 (FIB-4) index were calculated at baseline and during follow-up. The effects of Cana versus placebo on these NAFLD risk scores were assessed with linear mixed models. Multivariable cox regression models were used to assess associations between baseline NAFLD risk scores and clinical outcomes.

Results

4387 (99.6%) participants had data available to evaluate baseline NAFLD risk scores. During a median 2.6 years follow-up, Cana lowered hepatic steatosis index -0.28 (95%CI -0.18, -0.39; p<0.001) and attenuated increases in NAFLD fibrosis score -0.06 (-0.03, -0.10; p=0.001) (Figure). Cana did not affect FIB4-index (Figure). After adjusting for cardiometabolic risk factors, higher NAFLD fibrosis score and FIB-4 index were associated with increased risk of mortality (HR 1.51, 95%CI 1.12, 2.03, p=0.007; HR 2.04, 95%CI 1.17-3.61, p=0.01, respectively). NAFLD risk scores were not associated with CKD progression.

Conclusion

In patients with type 2 diabetes and CKD, Cana may improve hepatic steatosis and attenuate fibrosis. Further evaluation of the effects of sodium-glucose cotransporter 2 inhibition in individuals with NAFLD is warranted.

Effects of canagliflozin on (A) hepatic steatosis index, (B) NAFLD fibrosis score, and (C) FIB-4 index

Funding

  • Commercial Support