Effect of Dapagliflozin on Myocardial Insulin Sensitivity and Perfusion: Rationale and Design of The DAPAHEART Trial

• DOI: 10.1007/s13300-021-01083-1
• Publication Date: 2021-05-26T12:02:43Z
• Authors: Gian Pio Sorice; Francesca Cinti; Lucia Leccisotti; Domenico D’Amario; Margherita Lorusso; Maria Angela Guzz...; Teresa Mezza; Camilla Cocchi; Umberto Capece; Pietro Manuel Fer...; Filippo Crea; Alessandro Giordano; Patricia Iozzo; Andrea Giaccari
• Keywords: Dapagliflozin; Glycated hemoglobin

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to beneficial effects on various cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) primary prevention and those a high CV risk profile. However, the mechanism(s) responsible for these benefits remain elusive unexplained. The aim of DAPAHEART study will be demonstrate that treatment SGLT-2 is associated greater myocardial insulin sensitivity T2D, determine whether this improvement can attributed decrease whole-body (and tissue-specific) resistance increased perfusion and/or glucose uptake. We also there an appreciable degree myocardial-wall conditions subtended by affected non-affected coronary vessels, if relates changes left ventricular function.The trial phase III, single-center, randomized, two-arm, parallel-group, double-blind, placebo-controlled study. A cohort 52 T2D stable artery disease (without any previous history infarction, or without percutaneous intervention), suboptimal glycemic control (glycated hemoglobin [HbA1c] 7-8.5%) their current standard care anti-hyperglycemic regimen, randomized 1:1 ratio dapagliflozin placebo. outcome detect uptake from baseline 4 weeks after initiation. main secondary blood flow, as measured 13N-ammonia positron emission tomography/computed tomography (PET/CT). Other include cardiac function, skeletal muscle, adipose tissue, liver, brain kidney, assessed fluorodeoxyglucose (FDG) PET-CT imaging during hyperinsulinemic-euglycemic clamp; pericardial, subcutaneous visceral fat, browning observed CT images FDG studies; systemic sensitivity, clamp, control, urinary output; microbiota modification.SGLT-2 inhibitors, addition insulin-independent plasma glucose-lowering effect, are able directly (substrate availability, fuel utilization, sensitivity) well indirectly (cardiac after-load reduction, decreased factors heart failure) affect functions. Our provide novel insights into how drugs exert protection diabetic population.EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752.