The impact of canagliflozin on the risk of neuropathy events: A post-hoc exploratory analysis of the CREDENCE trial
Author(s)
Type
Journal Article
Abstract
AIM: Canagliflozin reduces the risk, and progression, of diabetic kidney disease. We hypothesized that it may improve the microvascular complication of neuropathy. METHODS: The CREDENCE trial randomized participants with type 2 diabetes and kidney disease to canagliflozin 100 mg daily or placebo. Neuropathy events were defined post-hoc as any reported adverse event consistent with a peripheral or autonomic neuropathy event. The effect of canagliflozin and predictors of neuropathy events were estimated using Cox regression analysis. In sensitivity analyses the endpoint was restricted to sensorimotor polyneuropathy, diabetic neuropathy, and non-autonomic neuropathy events. RESULTS: Almost half (48.8%) of the 4401 participants had a diagnosis of neuropathy at baseline. Over a median of 2.45 years of follow up, 657 people experienced a neuropathy event (63.2 per 1000 patient-years). Independent factors associated with higher risk of experiencing neuropathy events were non-white race, younger age, higher glycated haemoglobin and lower estimated glomerular filtration rate. The incidence of neuropathy events was similar in people randomized to canagliflozin and placebo (334/2202 vs. 323/2199; HR 1.04, 95% CI 0.89 to 1.21, P = 0.66). Canagliflozin had no impact on sensorimotor polyneuropathy (HR 0.93, 95% CI 0.69 to 1.25, P = 0.63), diabetic neuropathy (HR 0.91, 95% CI 0.68 to 1.22, P = 0.52), or non-autonomic neuropathy (HR 1.03, 95% CI 0.87 to 1.21, P = 0.77). The lack of effect on neuropathy events was consistent in subgroup analyses. CONCLUSION: Canagliflozin did not affect the risk of neuropathy events in the CREDENCE trial. Future large randomized studies with prespecified neuropathy endpoints are required to determine the impact of sodium glucose cotransporter 2 inhibitors on diabetic neuropathy.
Date Issued
2022-07-01
Date Acceptance
2022-02-08
Citation
Diabetes and Metabolism, 2022, 48 (4)
ISSN
1262-3636
Publisher
Elsevier Masson
Journal / Book Title
Diabetes and Metabolism
Volume
48
Issue
4
Copyright Statement
© 2022 Elsevier Masson SAS. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/35172198
PII: S1262-3636(22)00014-3
Subjects
Adverse event
Diabetic kidney disease
Diabetic neuropathy
Randomized controlled trial
Sodium Glucose Co-transporter Inhibitors
Publication Status
Published
Coverage Spatial
France
Article Number
ARTN 101331
Date Publish Online
2022-02-13