Play of Chance Versus Concerns Regarding Dipeptidyl Peptidase-4 Inhibitors: Heart Failure and Diabetes

The delicate balance of disease management versus off-target effects of treatment continues to be a vital concern to both patients and physicians. This article offers a brief overview of heart failure in diabetes and comments on the recent outcome trials of dipeptidyl peptidase-4 (DPP-4) inhibitors, with a closer look at a few pathobiological concerns.The importance of safe antidiabetic treatments becomes apparent when one considers the increasing obesity and diabetes pandemics. Approximately 150,000 patients with moderate-high cardiovascular (CV) risk factor profiles are currently enrolled in trials of antidiabetic agents. Establishing the CV safety of newer antidiabetic agents, especially with respect to heart failure, remains crucial.Heart failure syndrome is a symptom complex composed of worsening shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, fatigue, and the well-known manifestation of ankle edema. The syndrome is characterized by physical findings of fluid retention (dependent edema), a third heart sound, rales sounds, and distension of the neck veins. In addition, heart failure is associated with chronic inflammation and a prothrombotic state. Endothelial dysfunction and proteomic and neurohormonal activation occur many months before development of the syndrome complex.1,2Newer areas of basic science research have identified potential prognostic indicators in chronic heart failure (miR126 and miR508-5p) that might be used as novel markers leading to earlier diagnosis and treatment of heart failure.3,4 Heart failure has several etiologies ranging from mechanical and electrical dysfunction to structural and valvular abnormities. Moreover, the consequences of heart failure are multi-systemic and adversely affect the liver, kidneys, bone marrow, and muscle.Recent data from the Olmstead County population study5 showed that patients with diabetes had equal amounts of systolic and diastolic dysfunction. Patients with diabetes frequently have preserved left-ventricular function (a normal ejection fraction) but with a poorly compliant left ventricle that is …