James L Januzzi1, Javed Butler2, Petr Jarolim3, Naveed Sattar4, Ujjwala Vijapurkar5, Mehul Desai5, Michael J Davies6. 1. Department of Medicine/Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: jjanuzzi@partners.org. 2. Cardiology Division, Stony Brook University, Stony Brook, New York. 3. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 4. British Heart Foundation Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland. 5. Janssen Research & Development, LLC, Raritan, New Jersey. 6. Janssen Scientific Affairs, LLC, Titusville, New Jersey.
Abstract
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).
RCT Entities:
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).
Authors: Stephen J Greene; Muthiah Vaduganathan; Muhammad Shahzeb Khan; George L Bakris; Matthew R Weir; Jonathan H Seltzer; Naveed Sattar; Darren K McGuire; James L Januzzi; Norman Stockbridge; Javed Butler Journal: J Am Coll Cardiol Date: 2018-03-10 Impact factor: 24.094