China: Canagliflozin and Neuropathy Events in the CREDENCE Trial

A post-hoc exploratory analysis of the CREDENCE trial revealed that canagliflozin, an SGLT2 inhibitor, did not affect the risk of neuropathy events in the trial. The findings of the study were published in the journal Diabetes & Metabolism on 13 February 2022.

Canagliflozin is known to reduce the risk and progression of diabetic kidney disease. Jinlan Liao, Department of Nephrology, Peking University Shenzhen Hospital, Shenzhen, China, and colleagues hypothesized that it may improve the microvascular complication of neuropathy.

The CREDENCE trial included patients with type 2 diabetes and kidney disease. They were randomized to receive canagliflozin 100mg daily or placebo. Neuropathy events were defined post-hoc as any reported adverse event consistent with a peripheral or autonomic neuropathy event.

Cox regression analysis was used to estimate the effect of canagliflozin and predictors of neuropathy events. In sensitivity analyses, the endpoint was restricted to diabetic neuropathy, sensorimotor polyneuropathy, and non-autonomic neuropathy events.

Key Findings

• 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).
• Canagliflozin had no impact on sensorimotor polyneuropathy (HR 0.93), diabetic neuropathy (HR 0.91), or non-autonomic neuropathy (HR 1.03).
• The lack of effect on neuropathy events was consistent in subgroup analyses.

To conclude, canagliflozin did not affect the risk of neuropathy events in the CREDENCE trial. The researchers add that there is a need for future large randomized studies with prespecified neuropathy endpoints to determine the impact of sodium glucose cotransporter 2 inhibitors on diabetic neuropathy.

Reference

The study titled, "The impact of canagliflozin on the risk of neuropathy events: a post-hoc exploratory analysis of the CREDENCE trial," was published in the journal Diabetes & Metabolism.

DOI: https://doi.org/10.1016/j.diabet.2022.101331