Visual Abstract

Background: Canagliflozin reduces the incidence of kidney and cardiovascular events in people with type 2 diabetes and chronic kidney disease (CKD). We assessed the effects of canagliflozin according to age and sex in a randomized, placebo-controlled trial.

Methods: The CREDENCE study randomized participants with type 2 diabetes and albuminuric CKD. The effects of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of the serum creatinine level, or death from kidney or cardiovascular causes), and secondary outcomes were evaluated by age at baseline (<60, 60-69, and ≥70 years) and sex using Cox regression models.

Results: Of the 4401 participants, 33.5%, 42.1%, and 24.4% were <60, 60-69, and ≥70 years of age at baseline, respectively; 33.9% were female. Canagliflozin reduced the risk of the primary outcome (HR 0.70, 95% confidence interval 0.59 to 0.82; P <0.001) and key secondary outcomes. Effects were similar within each age group, and by sex (Figure 1A,B). The effect of canagliflozin on safety outcomes was consistent among age groups and by sex, including volume depletion, hypoglycemia and adverse events leading to drug withdrawal (all Pinteraction≥0.1).

Conclusion: Canagliflozin reduces the risk of kidney and cardiovascular events in people with type 2 diabetes and CKD with consistent effects and no differences in safety outcomes across subgroups defined by age and sex.


T. Yi: None. C. P. Cannon: Advisory Panel; Self; Aegerion Pharmaceuticals Inc., Amarin Corporation plc, Corvidia Therapeutics, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Sanofi, Consultant; Self; Alnylam Pharmaceuticals, Inc., Amgen Inc., Applied Therapeutics, Ascendis Pharma A/S, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, HLS Therapeutics Inc., Kowa Company, Ltd., Research Support; Self; Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Daiichi Sankyo, Janssen Research & Development, LLC, Kowa Company, Ltd., Merck & Co., Inc., Novo Nordisk Pharma Ltd., Pfizer Inc. D. De zeeuw: Consultant; Self; Boehringer Ingelheim International GmbH, Fresenius Medical Care, Retrophin, Inc., Other Relationship; Self; Bayer Healthcare Pharmaceuticals Inc. 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. 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. 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. H. Zhang: None. 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 & C

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