Abstract

LINAGLIPTIN: A DPP-4 INHIBITOR FOR THE POTENTIAL TREATMENT OF HEART FAILURE IN TYPE-2 DIABETIC PATIENTS

Dr. A. R. Shabaraya and Nikhil Benroy Noronha*

Abstract

A series of metabolic illnesses known as diabetes mellitus are characterised by chronic hyperglycemia brought on by deficiencies in insulin secretion, insulin action, or both. DPP-4 inhibitors, known as gliptins, are a class of oral diabetic medications approved by the Food and Drug Administration (FDA) to treat type 2 diabetes mellitus in adults. DPP-4 is a ubiquitous enzyme that acts on incretin hormones, mainly GLP-1 (glucagon-like peptide-1) and GIP (gastric inhibitory peptide), which maintain glucose homeostasis by increasing insulin secretion and decreasing glucagon secretion. Linagliptin is a DPP-4 inhibitor that was recently approved as a once-daily oral glucoselowering drug in the USA, Japan, and Europe. Diastolic dysfunction (DD) is one of the early manifestations of CVD in insulin resistant conditions, such as obesity and T2DM and can be identified clinically by echocardiographic findings. Linagliptin-treated rats exhibited significant improvement in impaired LV diastolic function, as well as endothelial function of gastrocnemius feed arteries, and, somewhat surprisingly, this was associated with a reduction in BP. Both pre-clinical and clinical studies have shown beneficial effects of linagliptin on CV dysfunction associated with obesity and diabetes. Blood pressure (BP) responses to DPP-4 inhibitor therapy in humans are either neutral or modestly reduced. There was no heterogeneity of linagliptin effects on baseline estimated glomerular filtration rate or urine albumin-creatinine ratio, or prerandomization left ventricular ejection fraction. Linagliptin has positive benefits on the cardiovascular system beyond those associated with class effects and glycemic management.

Keywords: Linagliptin, DPP-4 Inhibitor, Gliptins, Diabetes, Heart failure.