Effects of canagliflozin on initiation of insulin and other antihyperglycaemic agents in the CANVAS Program

David R Matthews, Carol Wysham, Melanie Davies, April Slee, Maria Alba, Mary Lee, Vlado Perkovic, Kenneth W Mahaffey, Bruce Neal, David R Matthews, Carol Wysham, Melanie Davies, April Slee, Maria Alba, Mary Lee, Vlado Perkovic, Kenneth W Mahaffey, Bruce Neal

Abstract

This study compared initiation of insulin and other antihyperglycaemic agents (AHAs) with canagliflozin versus placebo for participants with type 2 diabetes and a history/high risk of cardiovascular disease in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. After 1 year, fewer participants treated with canagliflozin versus placebo initiated any AHA (7% vs. 16%), insulin (3% vs. 9%) or any non-insulin AHA (5% vs. 12%) (P < .001 for all); overall AHA initiation rates increased over time but were consistently lower with canagliflozin compared with placebo. During the study, the likelihood of initiating insulin was 2.7 times lower for participants treated with canagliflozin compared with placebo (hazard ratio, 0.37; 95% CI: 0.31, 0.43; P < .001). The time difference between 10% of patients in the canagliflozin and placebo groups being initiated on insulin from the beginning of the trial was about 2 years. Time to initiation of other AHAs, including metformin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sulphonylureas, was also delayed for canagliflozin versus placebo (P < .001 for each). Compared with placebo, canagliflozin delayed the need for initiation of other AHAs and delayed time to insulin therapy, an outcome that is important to many people with diabetes.

Trial registration: ClinicalTrials.gov NCT01032629 NCT01989754.

Keywords: SGLT2 inhibitor; antihyperglycaemic agent; insulin; type 2 diabetes.

Conflict of interest statement

D.R.M. has served on advisory boards and as a consultant for Novo Nordisk, Novartis, Sanofi‐Aventis, and Servier and has given lectures for Novo Nordisk, Servier, Sanofi‐Aventis, Novartis, Mitsubishi Tanabe and Aché Laboratories. C.W. has served as a consultant for Janssen. M.D. has acted as consultant, advisory board member and speaker for Novo Nordisk, Sanofi‐Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca and Janssen, has served as an advisory board member for Servier and Gilead Sciences Ltd., has served as a speaker for NAPP, Mitsubishi Tanabe Pharma Corporation and Takeda Pharmaceuticals International Inc. and has received grants in support of investigator trials from Novo Nordisk, Sanofi‐Aventis, Lilly, Boehringer Ingelheim, AstraZeneca and Janssen. A.S. is a full‐time employee of Axio Research, which received payment from Janssen for statistical support of the analyses reported in this manuscript. M.A. and M.L. were full‐time employees of Janssen Research & Development, LLC at the time of study. V.P. has received fees for advisory boards, steering committee roles or scientific presentations from AbbVie, Astellas, AstraZeneca, Bayer, Baxter, BMS, Boehringer Ingelheim, Dimerix, Durect, Eli Lilly, Gilead, GSK, Janssen, Merck, Mitsubishi Tanabe, Mundipharma, Novartis, Novo Nordisk, Pfizer, PharmaLink, Relypsa, Retrophin, Sanofi, Servier, Vifor and Tricida. K.W.M.'s disclosures can be viewed at http://med.stanford.edu/profiles/kenneth-mahaffey. B.N. is supported by an Australian National Health and Medical Research Council Principal Research Fellowship, holds a research grant for this study from Janssen and has held research grants for other large‐scale cardiovascular outcome trials from Roche, Servier and Merck Schering Plough; his institution has received consultancy, honoraria or travel support for contributions he has made to advisory boards and/or the continuing medical education programmes of Abbott, Janssen, Novartis, Pfizer, Roche, and Servier.

© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Time to initiation of insulin in the subset of participants not previously on insulin. CI, confidence interval; HR, hazard ratio
FIGURE 2
FIGURE 2
Time to initiation of other antihyperglycaemic agents in the subsets of participants not previously on these agents. A, Metformin. B, DPP‐4 inhibitors. C, GLP‐1 receptor agonists. D, Sulphonylureas. CI, confidence interval; DPP‐4, dipeptidyl peptidase‐4; GLP‐1, glucagon‐like peptide‐1; HR, hazard ratio

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Source: PubMed

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