131-LB: The Impact of Canagliflozin on the Risk of Neuropathy Events: Results from the CREDENCE Trial

Background: Sodium-glucose cotransporter 2 inhibitors reduce the risk, and progression, of diabetic kidney disease. We hypothesized that sodium-glucose cotransporter 2 inhibitors could similarly improve the microvascular complication of neuropathy. Methods: The CREDENCE trial randomized participants with type 2 diabetes and albuminuria to canagliflozin or placebo. Neuropathy events were defined as any reported adverse event with a Medical Dictionary for Regulatory Activities (MedDRA) term consistent with peripheral or autonomic neuropathy. The effect of canagliflozin on neuropathy events was calculated by Cox regression. In secondary analyses the endpoint was restricted to sensorimotor polyneuropathy, diabetic neuropathy, or non-autonomic neuropathy events, and subgroups were analysed. P-values adjusted for multiplicity using the Holm-Bonferroni correction were derived for the subgroup analyses. Results: Half (48.8%) of the 4401 participants had a diagnosis of neuropathy at baseline. Over a median of 2.45 years follow up, 657 people experienced a neuropathy event (63.2 per 1000 patient-years). 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. Conclusions: Canagliflozin did not affect the risk of neuropathy events in the CREDENCE trial despite clear benefits for nephropathy, cardiovascular disease and glycemic control.