131-LB: The Impact of Canagliflozin on the Risk of Neuropathy Events: Results from the CREDENCE Trial
Authors: LIAO JINLAN , KANG AMY , XIA CHAO , ARNOTT CLARE , TANNA GIAN LUCA DI , KRISHNAN ARUN V. , POLLOCK CAROL A. , AGARWAL RAJIV , BAKRIS GEORGE , HEERSPINK HIDDO L. , LEVIN ADEERA , DE ZEEUW DICK , NEAL BRUCE , ZHANG HONG , WHEELER DAVID C. , ZINMAN BERNARD , MAHAFFEY KENNETH W. , PERKOVIC VLADO , JARDINE MEG J. , SMYTH BRENDAN 
Published: June 2021

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.

Disclosure
J. Liao: None. H. L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook, CSL Behring, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, LLC, Merck & Co., Inc., Mitsubishi Corporation Life Sciences Limited, Mundipharma International, Novo Nordisk, Retrophin, Inc., Research Support; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC. A. Levin: Advisory Panel; Self; AstraZeneca, Johnson & Johnson, Research Support; Self; Boehringer Ingelheim International GmbH. D. De zeeuw: Consultant; Self; Boehringer Ingelheim International GmbH, Fresenius Medical Care, Retrophin, Inc., Other Relationship; Self; Bayer Healthcare Pharmaceuticals Inc. B. Neal: Advisory Panel; Self; Abbott, Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Roche Pharma, Servier Laboratories, Research Support; Self; Janssen Pharmaceuticals, Inc., Merck Schering Plough, Roche Pharma, Servier Laboratories. H. Zhang: None. D. C. Wheeler: Advisory Panel; Self; Merck Sharp & Dohme Corp., Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, GlaxoSmithKline plc., Janssen Global Services, LLC., Mundipharma International, Tricida, Inc., Speaker’s Bureau; Self; Amgen Astellas BioPharma, Astellas Pharma Inc., Napp Pharmaceuticals, Vifor Pharma Management Ltd. B. Zinman: Advisory Panel; Self; Abbott Diabetes, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk, Sanofi. K. W. Mahaffey: Consultant; Self; Abbott, Amgen Inc., Anthos, AstraZeneca, Baim Institute for Clinical Research, Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals, Inc., CSL Behring, Elsevier, Inova, Intermountain Health, Johnson & Johnson, Medscape, Mount Sinai, Mundipharma International, MyoKardia, National Institutes of Health, Novartis Pharmaceuticals Corporation, Novo Nordisk, Otsuka America Pharmaceutical, Inc., Portola Pharmaceuticals, Inc., Regeneron Pharmaceuticals Inc., SmartMedics, Theravance Biopharma, Research Support; Self; Afferent, AHA, Amgen Inc., Apple, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Cardiva Medical, Inc, Eidos, Ferring Pharmaceuticals Inc., Gilead Sciences, Inc., Google, Johnson & Johnson, Luitpold Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., National Institutes of Health, Novartis Pharmaceuticals Corporation, Sanifit, Sanofi, St. Jude Medical. V. Perkovic: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Baxter, Bayer AG, Boehringer Ingelheim (Canada) Ltd., Bristol-Myers Squibb Company, Eli Lilly Japan K. K., Gilead Sciences, Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Retrophin, Inc., Roche Pharma, Sanofi, Servier Laboratories. M. J. Jardine: Advisory Panel; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Intern