Effects of empagliFlozin on myocardIal metabOlic Rate of glucosE Estimated Through 18FDG PET (FIORE Study)

Sponsor
University of Catanzaro
Study ID
NCT04183868
Phase
PHASE4
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
45 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Empagliflozin 10 MG — DRUG
    10 mg tablet daily
  • Glimepiride 2 mg — DRUG
    starting dose: 2 mg tablet daily, 1 mg for lunch and 1 mg for dinner, can undergo to up-titration of glimepiride to a maximum of 6 mg daily

Study Details

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.

Key Dates

Start date
Apr 30, 2016
Status verified
Jan 2023
Primary completion
Oct 31, 2021
Completion
Oct 31, 2021

Study Design

Enrollment
26 participants (actual)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION

Arms

  • Experimental: Empagliflozin
    Eligible patients (meeting all inclusion criteria) will be randomized to receive empagliflozin in addition to existing metformin background therapy (daily dose of ≥1.500 mg, which has to remain unchanged throughout the study) for 26 weeks. At the end of 26 weeks of treatment, subjects belonging to empagliflozin arm will be shifted to glimepiride treatment.
  • Active Comparator: Glimepiride
    Eligible patients will be randomized to receive glimepiride (starting dose: 2 mg daily) treatment arm, can undergo to up-titration of glimepiride to a maximum of 6 mg/day, if they experience fasting plasma glucose (FPG) levels \> 112 mg/dl (6,2 mmol/l) at scheduled visit at 6th week or at any later scheduled visit. Whereas, glimepiride-treated patients experiencing recurrent hypoglycemic episodes should down-titrate glimepiride to a dose, considered as appropriate by Investigator. Hypoglycemic events are defined as symptoms suggestive of low blood glucose confirmed by self monitored blood glucose (SMBG) \< 56 mg/dl (3,1 mmol/l). Severe hypoglycemia is defined as any hypoglycemic episode requiring the assistance of another party for recovery. At the end of 26 weeks of treatment, subjects belonging to glimepiride arm will be shifted to treatment with empagliflozin for 26 weeks.

Primary Outcome Measure

Change of myocardial metabolic rate of glucose [ Time Frame: Baseline, after 26 and 52 weeks ]

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