Author + information
- Received June 1, 2017
- Accepted June 8, 2017
- Published online July 31, 2017.
- James L. Januzzi Jr., MDa,∗ (, )
- Javed Butler, MD, MPH, MBAb,
- Petr Jarolim, MD, PhDc,
- Naveed Sattar, PhDd,
- Ujjwala Vijapurkar, PhDe,
- Mehul Desai, MDe and
- Michael J. Davies, PhDf
- aDepartment of Medicine/Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- bCardiology Division, Stony Brook University, Stony Brook, New York
- cDepartment of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- dBritish Heart Foundation Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland
- eJanssen Research & Development, LLC, Raritan, New Jersey
- fJanssen Scientific Affairs, LLC, Titusville, New Jersey
- ↵∗Address for correspondence:
Dr. James L. Januzzi Jr., Massachusetts General Hospital, Cardiology/Internal Medicine, 55 Fruit Street #148, Boston, Massachusetts 02114.
Background Sodium glucose co-transporter 2 inhibitors may reduce cardiovascular and heart failure risk in patients with type 2 diabetes mellitus (T2DM).
Objectives The goal of this study was to examine the effects of canagliflozin on cardiovascular biomarkers in older patients with T2DM.
Methods In 666 T2DM patients randomized to receive canagliflozin 100 or 300 mg or placebo, the study assessed the median percent change in serum N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), soluble (s)ST2, and galectin-3 from baseline to 26, 52, and 104 weeks.
Results Both serum NT-proBNP and serum hsTnI levels increased in placebo recipients, but they remained largely unchanged in those randomized to canagliflozin. Hodges-Lehmann estimates of the difference in median percent change between pooled canagliflozin and placebo were −15.0%, −16.1%, and −26.8% for NT-proBNP, and −8.3%, −11.9%, and −10.0% for hsTnI at weeks 26, 52, and 104, respectively (all p < 0.05). Serum sST2 was unchanged with canagliflozin and placebo over 104 weeks. Serum galectin-3 modestly increased from baseline with canagliflozin versus placebo, with significant differences observed at 26 and 52 weeks but not at 104 weeks. These results remained unchanged when only patients with complete samples were assessed.
Conclusions Compared with placebo, treatment with canagliflozin delayed the rise in serum NT-proBNP and hsTnI for over 2 years in older T2DM patients. These cardiac biomarker data provide support for the beneficial cardiovascular effect of sodium glucose co-transporter 2 inhibitors in T2DM. (A Safety and Efficacy Study of Canagliflozin in Older Patients [55 to 80 Years of Age] With Type 2 Diabetes Mellitus; NCT01106651)
- cardiovascular stress
- high-sensitivity troponin
- N-terminal pro–B-type natriuretic peptide
- sodium glucose co-transporter 2 inhibitor
- soluble ST2
This study was sponsored by Janssen Scientific Affairs, LLC, and Janssen Global Services, LLC, funded the medical writing support. Dr. Januzzi has received research support from Janssen, Boehringer Ingelheim, Novartis, Roche Diagnostics, Siemens, Prevencio, Singulex, and Amgen; has served as a consultant for Janssen, Abbott, Boehringer Ingelheim, Novartis, Roche Diagnostics, and Philips; and has served on clinical endpoints adjudication committees for AbbVie and Pfizer. Dr. Butler has served as a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CardioCell, CVRx, Janssen, Merck, Novartis, Relypsa, Vifor Pharma, and ZS Pharma. Dr. Jarolim has received research support through his institution from Abbott Laboratories, AstraZeneca, Daiichi-Sankyo, GlaxoSmithKline, Janssen, Merck, Roche Diagnostics, Takeda Global Research and Development Center, and Waters Technologies Corporation. Dr. Sattar has served on advisory boards for Janssen, Boehringer Ingelheim, Eli Lilly, Amgen, and Novo Nordisk; and has received research support from AstraZeneca and Boehringer Ingelheim. Drs. Vijapurkar and Desai are full-time employees of Janssen Research & Development, LLC; and own stock in Johnson & Johnson. Dr. Davies is a full-time employee of Janssen Scientific Affairs, LLC; and owns stock in Johnson & Johnson. P.K. Shah, MD, served as Guest Editor-in-Chief, and Wolfgang Koenig, MD, served as Guest Editor for this article.
- Received June 1, 2017.
- Accepted June 8, 2017.
- 2017 The Authors