Effects of empagliFlozin on myocardIal metabOlic Rate of glucosE Estimated Through 18FDG PET (FIORE Study)
Status:
Unknown status
Trial end date:
2021-04-01
Target enrollment:
Participant gender:
Summary
Diabetes is an independent risk factor for ischemic heart disease (CAD) and heart failure,
and cardiovascular diseases are the main cause of mortality and morbidity in patients with
diabetes. Recent studies on cardiovascular outcomes have shown that type 2 sodium glucose
co-transporter (SGLT-2i) inhibitors are not only effective in improving glycometabolic
control, but are also able to reduce major CV events (MACE) and hospitalization for heart
failure. However, it is still unclear whether the beneficial CV effects of treatment with
SGLT2i are due to indirect mechanisms such as reduction in blood pressure, improvement of
vascular stiffness, reduction in body weight and visceral adiposity, reduction in uricemia or
whether they have effects direct on the heart. Recently, it was shown that in nondiabetic
porcine model with heart failure, the treatment with empagliflozin was associated with a
switch of myocardial fuel utilization from glucose uptake toward uptake of ketone bodies and
free fatty acid, thereby improving myocardial energetics, enhancing LV systolic function, and
ameliorating adverse LV remodeling.
It is not known whether empagliflozin treatment is able to modify the heart's energy
metabolism even in humans.
In this study we hypothesize that empagliflozin may determine beneficial CV effects reducing
myocardial metabolic rate of glucose assessed by hyperinsulinemic euglycemic clamp 18F-FDG
PET scans in patients with type 2 diabetes.
This is a single-center, prospective, controlled, randomized, open-label, two parallel group
and switch, active-comparator study that evaluates the comparative effects of 26 weeks of
treatment with empagliflozin versus glimepiride add on metformin on myocardial metabolic rate
of glucose estimated through 18F-FGD-PET scan in patients with type 2 diabetes without a
history of coronary heart disease. At the end of 26 weeks of treatment, subjects belonging to
the first group will be shifted to glimepiride therapy, while subjects belonging to the
second group will be shifted to empagliflozin treatment for 26 weeks. All subjects, then,
will control themselves.