The Serendipitous Story of SGLT2 Inhibitors in Heart Failure

Abstract

Diabetes intersects with cardiovascular disease at every level. While there has been much focus on understanding atherosclerotic complications, less well appreciated is the relationship between diabetes and heart failure. In addition to being a key and independent risk factor for the development of heart failure,1 diabetes is also one of the most important adverse prognostic factors in those with established heart failure with either reduced or preserved ejection fraction. 1,2 Diabetes is associated with a high prevalence of unrecognized left ventricular diastolic and systolic dysfunction, and accelerates the development of overt heart failure compared to similar patients without diabetes.3 In addition to cardiac predictors such as left ventricular dysfunction, hypertrophy, and coronary artery disease, features of diabetes associated with the development of heart failure include poor glycemic control, longer duration of diabetes, insulin treatment, and the presence of microvascular complications, such as retinopathy or nephropathy.2, 4 Finally, data from randomized trials and registries remind us that heart failure is numerically nearly as common as ischemic complications in patients with type 2 diabetes, and remains one of the leading causes of hospitalizations in this population.1, 2 While conventional risk factor control can reduce ischemic complications, heart failure risk remains a recalcitrant problem in diabetes for which intensive glycemic control has had little benefit.