TY - JOUR
T1 - The impact of canagliflozin on the risk of neuropathy events
T2 - A post-hoc exploratory analysis of the CREDENCE trial
AU - Liao, Jinlan
AU - Kang, Amy
AU - Xia, Chao
AU - Young, Tamara
AU - Di Tanna, Gian Luca
AU - Arnott, Clare
AU - Pollock, Carol
AU - Krishnan, Arun V.
AU - Agarwal, Rajiv
AU - Bakris, George
AU - Charytan, David M.
AU - de Zeeuw, Dick
AU - Heerspink, Hiddo J.L.
AU - Levin, Adeera
AU - Neal, Bruce
AU - Wheeler, David C.
AU - Zhang, Hong
AU - Zinman, Bernard
AU - Mahaffey, Kenneth W.
AU - Perkovic, Vlado
AU - Jardine, Meg J.
AU - Smyth, Brendan
N1 - Funding Information:
The CREDENCE study was sponsored by Janssen Research and Development , and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical. This post hoc analysis of the CREDENCE trial was not specifically funded. The funders were not involved in the design, analysis, reporting, or decision to submit this manuscript for publication. JL was supported by grants from the San-Ming Project of Medicine, Shenzhen (SZSM201812097) and the Medical Science and Technology Research Foundation of Guangdong Province (B2019025). AK is supported by an NHMRC Postgraduate Scholarship (1150349) via the University of New South Wales, an Australian Government Research Training Program Fee Offset and has received a George Institute Scholarship. TY was supported by a University Postgraduate Award via University of New South Wales. CX was supported by a scholarship from the China Scholarship Council. DMC reports personal fees from Janssen, during the conduct of the study. We thank the participants in this trial and thank the study investigators, who are listed in the Supplementary Appendix to the primary CREDENCE study publication.
Publisher Copyright:
© 2022 Elsevier Masson SAS
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - Adverse event
KW - Diabetic kidney disease
KW - Diabetic neuropathy
KW - Randomized controlled trial
KW - Sodium Glucose Co-transporter Inhibitors
U2 - 10.1016/j.diabet.2022.101331
DO - 10.1016/j.diabet.2022.101331
M3 - Article
C2 - 35172198
AN - SCOPUS:85126836391
SN - 1262-3636
VL - 48
JO - Diabetes and Metabolism
JF - Diabetes and Metabolism
IS - 4
M1 - 101331
ER -