Research LettersEffects of canagliflozin on cardiovascular, renal, and safety outcomes in participants with type 2 diabetes and chronic kidney disease according to history of heart failure: Results from the CREDENCE trial
Section snippets
Materials and methods
CREDENCE was a multicenter, double-blind, randomized trial of canagliflozin in participants with T2DM and nephropathy (ClinicalTrials.gov identifier: NCT02065791).4 As detailed previously, 4401 participants with hemoglobin A1c between 6.5% to 12.0%, an estimated glomerular filtration rate of 30 to <90 mL per minute per 1.73 m2 of body surface area, and elevated albuminuria (urinary albumin:creatinine ratio, >300-5000 mg/g) were randomized to canagliflozin 100 mg or placebo. Patients were
Results
A total of 652 (15%) participants had a history of HF. Participants with a prior history of HF were older (65 years vs 63 years), were more likely to be white (88% vs 63%) and female (39% vs 33%), had a shorter mean duration of diabetes (15 years vs 16 years), had a similar estimated glomerular filtration rate (57 mL/min/1.73 m2 vs 56 mL/min/1.73 m2), and had a higher prevalence of established atherosclerotic CV disease (81% vs 45%) compared to those without prior history of HF (Table I). More
Funding
This study was supported by Janssen Research & Development, LLC.
Discussion
Overall, canagliflozin safely reduced renal and CV events in participants with T2DM and nephropathy with consistent effects in patients with or without a prior history of HF. In patients without a prior history of HF, canagliflozin use was associated with robust effect sizes for the reduction of CV death and HHF and HHF alone. There is accumulating evidence regarding SGLT2 inhibitor efficacy specifically in patients with HF, including in patients with HF with reduced EF in the published
Conflict of Interest
Ashish Sarraju has nothing to disclose. JingWei Li has nothing to disclose. Christopher P. Cannon has received research grants from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Merck, Janssen, and Pfizer; and has received consulting fees from Aegerion, Alnylam, Amarin, Amgen, Applied Therapeutic, Ascendia, Boehringer Ingelheim, Bristol Myers Squibb, Corvidia, HLS Therapeutics, Innovent, Janssen, Kowa, Merck, Pfizer, and Sanofi. Tara I. Chang has received funding paid by
Acknowledgments
We thank all participants, investigators, and trial teams for their participation in the trial. CREDENCE was sponsored by Janssen Research & Development, LLC, and was conducted collaboratively by the sponsor, an academic-led steering committee, and an Academic Research Organization, George Clinical. Analyses were performed by George Clinical and independently confirmed by the sponsor. Technical editorial assistance was provided by Dana Tabor, PhD, of MedErgy, and was funded by Janssen
Data access and analysis
Ashish Sarraju had full access to the data in the study and takes responsibility for its integrity and the data analysis. Data from this study will be made available in the public domain via the Yale University Open Data Access Project (http://yoda.yale.edu/) once the product and relevant indication studied have been approved by regulators in the United States and European Union and the study has been completed for 18 months.
Credit author statement
Ashish Sarraju: Conceptualization, Writing – Original Draft, Writing – Review & Editing, Visualization; JingWei Li: Methodology, Formal analysis, Writing – Review & Editing; Christopher P. Cannon: Investigation, Writing – Review & Editing; Tara I. Chang: Investigation, Writing – Review & Editing; Rajiv Agarwal: Investigation, Writing – Review & Editing; George Bakris: Investigation, Writing – Review & Editing; David M. Charytan: Investigation, Writing – Review & Editing; Dick de Zeeuw:
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Cited by (0)
Clinical trial registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02065791.