Diabetes is associated with a substantially increased risk of heart failure, which is
associated with substantial morbidity and mortality. Despite the development of new
therapeutic strategies to improve glycemic control, recent clinical data from the saxagliptin
assessment of vascular outcomes recorded in patients with diabetes mellitus-thrombolysis in
myocardial infarction (SAVOR-TIMI) 53 study observed an unexpected finding of an excess of
adjudicated heart failure hospitalizations. This excess occurred in the setting of
pre-existing heart failure (HF) hospitalization and in those with elevated biomarkers for
heart failure such as N terminal pro Brain type natriuretic peptide (NT-pro BNP). A wealth of
preclinical data did not suggest a mechanistic basis for an excess of heart failure events,
however these preclinical studies primarily focused upon prevention based strategies as
opposed to regression studies once established heart failure was present. This proposal seeks
to understand if and how dipeptidyl peptidase-4 inhibitors (DPP4i,specifically saxagliptin)
may influence the development of heart failure, by evaluating changes in cardiac structure
and function using cardiac magnetic resonance imaging (MRI).
Phase:
Phase 4
Details
Lead Sponsor:
St. Michael's Hospital, Toronto Unity Health Toronto