Umberto Capece (1), Francesca Cinti (1), Gian Pio Sorice (2), Lucia Leccisotti (1), Margherita Lorusso (1), Michela Brunetti (1), Simona Moffa (1), Gianfranco Di Giuseppe (1), Gea Ciccarelli (1), Laura Soldovieri (1), Teresa Mezza (1), Patricia Iozzo (3), Alfredo Pontecorvi (1), Alessandro Giordano (1), Andrea Giaccari (1)
(1) Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, (2) Internal Medicine ,Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy, (3) Institute of Clinical Phisiology, National Research Council (CNR), Pisa, Italy
Background: Dapagliflozin treatment has been recently associated to an increase on myocardial flow reserve in patients with Type 2 Diabetes (T2D) without obstructive coronary artery disease. Many mechanisms could be responsible for this protective effect, including a reduction in the volume of epicardial adipose tissue (EAT), whose increase through the release of cytokines negatively affects coronary atherogenesis and cardiac function.Aim: We aimed to investigate the effects of the SGLT-2i dapagliflozin on EAT metabolism in patients with T2D and stable coronary artery disease.Methods: We performed a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The visceral (epicardial, mediastinal, infrarenal) and subcutaneous adipose tissue thickness and glucose uptake (EAT-GU) have been assessed at baseline and 4 weeks after treatment initiation by [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. Results: The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). Treatment with dapagliflozin resulted in a numerical increase in insulin sensitivity (p=0.06). Dapagliflozin treatment significantly reduces only EAT thickness by 19 % (p= 0.03). The reduction of EAT thickness paralleled the significant 21.6 % reduction in EAT-GU during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p=0.014).Conclusions: These data suggest that SGLT2 inhibitors reduce atherogenic epicardial adipose tissue thickness, validating the cardioprotective effects of these drugs. In addition, the decrease in glucose uptake documented by FDG-PET may indicate a reduction of epicardial adipose tissue inflammation, providing a new explanation of cardio-protective effects of SGLT-2i treatment.
