SAVOR-TIMI 53 was the first FDA-mandated cardiovascular outcome trial to be presented and published. It compared saxagliptin and placebo in 16,492 patients with type 2 diabetes. SAVOR-TIMI 53 demonstrated non-inferiority for major cardiovascular events (cardiovascular death, myocardial infarction, stroke) but not superiority. An unexpected statistically significant increase in adjudicated hospitalisation for heart failure was seen in the saxagliptin group. Post hoc analysis demonstrated that subjects at greatest risk for hospitalisation for heart failure had previous heart failure, an estimated glomerular filtration rate <60 mL/min, or elevated baseline levels of N-terminal pro-B type natriuretic peptide. As other dipeptidyl peptidase 4 (DPP-4) inhibitors are available which have not been associated with an increased risk of hospitalisation for heart failure, saxagliptin should be avoided in patients with heart failure or a reduced estimated glomerular filtration rate.
Variability in estimated glomerular filtration rate and patients' outcomes in a real‐world heart failure population
