Effects of Canagliflozin on Cardiovascular Biomarkers in Older Adults With Type 2 Diabetes

J Am Coll Cardiol. 2017 Aug 8;70(6):704-712. doi: 10.1016/j.jacc.2017.06.016. Epub 2017 Jun 12.


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).

Keywords: N-terminal pro–B-type natriuretic peptide; cardiovascular stress; galectin-3; high-sensitivity troponin; sodium glucose co-transporter 2 inhibitor; soluble ST2.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Canagliflozin / therapeutic use*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / etiology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood*
  • Peptide Fragments / blood*
  • Time Factors
  • Troponin I / blood*


  • Biomarkers
  • Blood Glucose
  • Hypoglycemic Agents
  • Peptide Fragments
  • Troponin I
  • pro-brain natriuretic peptide (1-76)
  • Canagliflozin
  • Natriuretic Peptide, Brain

Associated data

  • ClinicalTrials.gov/NCT01106651