Author + information
- Received June 1, 2017
- Accepted June 8, 2017
- Published online June 12, 2017.
- James L. Januzzi Jr., MDa,∗ (, )
- Javed Butler, MD, MPH, MBAb,
- Petr Jarolim, MD, PhDc,
- Naveed Sattar, PhD, FRCPd,
- Ujjwala Vijapurkar, PhDe,
- Mehul Desai, MDe and
- Michael J. Davies, PhDf
- aMassachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- bCardiology Division, Stony Brook University, Stony Brook, New York
- cBrigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- dBHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom
- eJanssen Research & Development, LLC, Raritan, New Jersey
- fJanssen Scientific Affairs, LLC, Titusville, New Jersey
- ↵∗Address for correspondence: James L. Januzzi, Jr, MD Massachusetts General Hospital 55 Fruit St #148 Boston, Massachusetts 02114 Phone: 617-724-6750 Fax: 617-643-1620, .
Background Sodium glucose co-transporter 2 (SGLT2) inhibitors may reduce cardiovascular and heart failure risk in patients with type 2 diabetes mellitus (T2DM).
Objectives 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, we assessed 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 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 to placebo, treatment with canagliflozin delayed rise in serum NT-proBNP and hsTnI over 2 years in older T2DM patients. These cardiac biomarker data provide support for beneficial cardiovascular effect of SGLT2 inhibitors in T2DM.
- sodium glucose co-transporter 2 inhibitor
- cardiovascular stress
- N-terminal pro-B type natriuretic peptide
- high-sensitivity troponin
- soluble ST2
Funding: This study was sponsored by Janssen Scientific Affairs, LLC (Titusville, New Jersey). Medical writing support was provided by Alaina Mitsch, PhD, of MedErgy (Yardley, Pennsylvania), and was funded by Janssen Global Services, LLC (Raritan, New Jersey).
Disclosures: J.L.J. has received research support from Janssen, Boehringer Ingelheim, Novartis, Roche Diagnostics, Siemens, Prevencio, Singulex, and Amgen, and has served as a consultant for Janssen, Boehringer Ingelheim, Novartis, Roche Diagnostics, and Philips. J.B. has served as a consultant for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CardioCell, CVRx, Janssen, Merck, Novartis, Relypsa, Vifor Pharma, and ZS Pharma. P.J. has received research support through his institution from Abbott Laboratories, AstraZeneca, LP, GlaxoSmithKline, Janssen Scientific Affairs, LLC, Merck & Co., Inc., Roche Diagnostics Corporation, Takeda Global Research and Development Center, and Waters Technologies Corporation. N.S. 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. U.V. and M.D. are full-time employees of Janssen Research & Development, LLC. M.J.D. is a full-time employee of Janssen Scientific Affairs, LLC.
- Received June 1, 2017.
- Accepted June 8, 2017.