Effects of 26 weeks of treatment with empagliflozin versus glimepiride on the myocardial glucose metabolic rate in patients with type 2 diabetes: The randomized, open‐label, crossover, active‐comparator FIORE trial

AIM: To determine whether treatment with empagliflozin was able to affect the myocardial glucose metabolic rate, as assessed by cardiac dynamic (18)F‐fluorodeoxyglucose‐positron emission tomography ((18)F‐FDG‐PET) combined with euglycaemic‐hyperinsulinaemic clamp compared with glimepiride in patients with type 2 diabetes. MATERIALS AND METHODS: To further investigate the cardioprotective mechanism of sodium‐glucose co‐transporter‐2 inhibitors, we performed a 26‐week, randomized, open‐label, crossover, active‐comparator study to determine the effects of empagliflozin 10 mg versus glimepiride 2 mg daily on the myocardial glucose metabolic rate assessed by cardiac dynamic (18)F‐FDG‐PET combined with euglycaemic‐hyperinsulinaemic clamp in 23 patients with type 2 diabetes. We also measured cardiac geometry and myocardial mechano‐energetic efficiency, as well as systolic and diastolic function by echocardiography. RESULTS: Compared with glimepiride, treatment with empagliflozin resulted in a greater reduction in the myocardial glucose metabolic rate from baseline to 26 weeks (adjusted difference −6.07 [−8.59, −3.55] μmol/min/100 g; P < .0001). Moreover, compared with glimepiride, empagliflozin led to significant reductions in left atrial diameter, left ventricular end‐systolic and end‐diastolic volumes, N‐terminal pro b‐type natriuretic peptide levels, blood pressure, heart rate, stroke work, and myocardial oxygen consumption estimated by the rate pressure product, and increases in ejection fraction, myocardial mechano‐energetic efficiency, red blood cells, and haematocrit and haemoglobin levels. CONCLUSIONS: The present study provides evidence that empagliflozin treatment in subjects with type 2 diabetes without coronary artery disease leads to a significant reduction in the myocardial glucose metabolic rate.