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The impact of canagliflozin on the risk of neuropathy events: a post-hoc exploratory analysis of the CREDENCE trial

Liao, Jinlan; Kang, Amy; Xia, Chao; Young, Tamara; Tanna, Gian Luca Di; Arnott, Clare; Pollock, Carol; ... Smyth, Brendan; + view all (2022) The impact of canagliflozin on the risk of neuropathy events: a post-hoc exploratory analysis of the CREDENCE trial. Diabetes & Metabolism , 48 (4) , Article 101331. 10.1016/j.diabet.2022.101331. Green open access

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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 100mg 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.

Type: Article
Title: The impact of canagliflozin on the risk of neuropathy events: a post-hoc exploratory analysis of the CREDENCE trial
Location: France
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.diabet.2022.101331
Publisher version: https://doi.org/10.1016/j.diabet.2022.101331
Language: English
Keywords: Adverse event, Diabetic kidney disease, Diabetic neuropathy, Randomized Controlled Trial, Sodium Glucose Co-transporter Inhibitors
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10144060
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