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

NCT04183868 | Completed Phase 4 DMC

• 1 other identifier: 2016.43
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes; Cardiovascular Risk Factor

Keywords

Empagliflozin; Type 2 diabetes; Myocardial glucose uptake; Cardiovascular risk

Outcome Measures

Primary Outcomes (1)

• Change of myocardial metabolic rate of glucose

  To assess whether empagliflozin treatment is able to determine a change of myocardial metabolic rate of glucose estimated through hyperinsulinemic euglycemic clamp 18FDG-PET scan, than glimepiride treatment (both in addition to metformin), in patients with T2DM without a history of coronary heart disease.

  Baseline, after 26 and 52 weeks

Secondary Outcomes (9)

• Change of glycemic parameters

  Baseline, after 26 and 52 weeks

• Change of insulin sensitivity

  Baseline, after 26 and 52 weeks

• Change of blood pressure

  Baseline, after 26 and 52 weeks

• Change of left ventricular systolic and diastolic function

  Baseline, after 26 and 52 weeks

• Change of pro-BNP

  Baseline, after 26 and 52 weeks

Study Arms (2)

Empagliflozin

EXPERIMENTAL

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.

Drug: Empagliflozin 10 MG

Glimepiride

ACTIVE COMPARATOR

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.

Drug: Glimepiride 2 mg

Interventions

Empagliflozin 10 MG DRUG

10 mg tablet daily

Also known as: Jardiance

Empagliflozin

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

Also known as: Solosa, Amaryl

Glimepiride

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes, in treatment with metformin
• Written informed consent

You may not qualify if:

• Type 1 diabetes
• eGFR \<60 ml/min/1.73 m2. or dialysis patients
• HbA1c \<6.5 o \>9%
• Previous treatment with insulin (except for short-term treatment with insulin in connection with intercurrent illness, at the discretion of the Investigator), with SGLT2 inhibitors or with GLP-1R agonists or DPPIV inhibitors
• Patients who do not tolerate empagliflozin and/or glimepiride or in whom empagliflozin and/or glimepiride are contraindicated
• Uncontrolled hypertension (BP\>140/90 mmHg)
• Prior cardio- cerebral-vascular events
• Hepatic disease
• Pathology neoplastic (past or present)
• Pregnancy women or childbearing female without adequate and approved birth control method

Sponsors & Collaborators

• University of Catanzaro: lead

Study Sites (1)

Universital Hospital Mater Domini

Catanzaro, 88100, Italy

Location

Related Publications (22)

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MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

empagliflozin; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Giorgio Sesti, MD

  University Sapienza of Rome

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor in Internal Medicine

Model Details: 52-weeks, single-center, prospective, controlled, randomized, open-label, two parallel group and switch, active-comparator. 13 subjects with T2DM, poorly controlled on metformin monotherapy, and without a history of ischemic heart disease, will be treated with empagliflozin for 26 weeks and will be compared with a group of 13 subjects with T2DM, poorly controlled on metformin monotherapy, and without a history of ischemic heart disease, treated with glimepiride (both in addition to metformin) for 26 weeks. 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.

Study Record Dates

• First Submitted: November 11, 2019
• First Posted: December 3, 2019
• Study Start: April 1, 2016
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: January 18, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Beginning 6 months and ending 36 months following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal. Proposals should be directed to succurro@unicz.it. To gain access, data requestors will need to sign a data access agreement.

Locations

IT (1)