Fibroblast Growth Factor-23 and Klotho in Heart Failure and Type 2 Diabetes Mellitus

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Recently, the US-regulatory authority the Food and Drug Administration (FDA) added a heart failure warning regarding novel type 2-diabetes drugs that contain the dipeptidyl peptidase-4 inhibitors saxagliptin and alogliptin. The phosphaturic hormone Fibroblast Growth Factor-23 (FGF-23) and its co-receptor klotho emerged as a novel promising biomarker in prognostication of cardiovascular mortality and morbidity. Thus, biomarker indicative of heart failure progression may be useful to guide therapy with gliptins.I hereby apply for a research fellowship at the TIMI study group to promote my training as a clinical scientist. The first project will be an additional analysis of the EXAMINE trial to elucidate the role of FGF-23 and klotho in regard to cardiovascular mortality and morbidity. The EXAMINE trial was conducted as a non-inferiority study comparing alogliptin with placebo with respect to major cardiovascular events in 5380 patients with type 2 diabetes and recent acute coronary syndromes. In addition, we aim to identify both patients at highest risk for cardiac decompensation and patients who benefit particularly from therapy with alogliptin.