Investigating the roles of hyperglycaemia, hyperinsulinaemia and elevated free fatty acids in cardiac function in patients with type 2 diabetes via treatment with insulin compared with empagliflozin: protocol for the HyperCarD2 randomised, crossover trial.

introductionType 2 diabetes (T2D) is characterised by elevated plasma glucose, free fatty acid (FFA) and insulin concentrations, and this metabolic profile is linked to diabetic cardiomyopathy, a diastolic dysfunction at first and increased cardiovascular disease (CVD) risk. Shifting cardiac metabolism towards glucose utilisation has been suggested to improve cardiovascular function and CVD risk, but insulin treatment increases overall glucose oxidation and lowers lipid oxidation, without reducing CVD risk, whereas SGLT2 inhibitors (SGLT2i) increase FFA, ketone body concentrations and lipid oxidation, while decreasing insulin concentrations and CVD risk. The aim of the present study is to elucidate the importance of different metabolic profiles obtained during treatment with a SGLT2i versus insulin for myocardial function in patients with T2D. METHODS AND ANALYSES: Randomised, crossover study, where 20 patients with T2D and body mass index>28 kg/m ETHICS AND DISSEMINATION: This study is approved by the Danish Medicines Agency (ref. nr.: 2017061587), the Danish Data Protection Agency (ref. nr.: AHH-2017-093) and the Capital Region Ethics Committee (ref. nr.: H-17018846). The trial will be conducted in accordance with ICH-GCP guidelines and the Declaration of Helsinki and all participants will provide oral and written informed consent. Our results, regardless of outcome, will be published in relevant scientific journals and we also will seek to disseminate results through presentations at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT: 2017-002101.