Effects of SGLT2 Inhibition on Myocardial Insulin Sensitivity

NCT03313752 | Completed Phase 3

• 1 other identifier: 2016-003614-27
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase III, single-centre, randomized, 2-arm, parallel-group, double blind, placebo-controlled study, consisting of a screening phase (Days -14 to -1), a 4-week double-blind, placebo-controlled treatment phase and a 4-week follow-up phase. Subjects: Type 2 diabetic patients and coronary artery diseases (CAD) not requiring revascularization or underwent percutaneous coronary intervention (PCI) but clinically stable at time of screening visit, with suboptimal glycaemic control (HbA1c 7.0-8.5%) on their current anti-hyperglycaemic regimen Subjects will be randomized in a 1:1 ratio to dapagliflozin or placebo. Subjects will undergo screening assessment in the 14-day period preceding administration of the first dose of study drug on Day 1. The primary Objective is to assess the effect of dapagliflozin on myocardial insulin sensitivity The Secondary Objective is to assess global heart function, and metabolic systemic effects of dapagliflozin, and glycemic control. The study aims to enroll patients with type 2 diabetes with suboptimal glycemic control, and with coronary artery diseases (CAD) not requiring revascularization or underwent percutaneous coronary intervention (PCI) but clinically stable, who have already undergone, under routine cardiological assessment, a positron emission tomography (PET) 13NH3 scan in order to assess the cardiovascular function. Thus, the study aims to assess whether the improvement in cardiac metabolism obtained with dapagliflozin is greater than that obtained with normal clinical practice (according to Standards of Care).

Conditions

Type2 Diabetes Mellitus; Stable Coronary Artery Disease

Keywords

diabetes, heart, dapagliflozin,

Outcome Measures

Primary Outcomes (1)

• Effect of dapagliflozin on myocardial insulin sensitivity

  Myocardial Glucose Uptake (MGU) umol/min/gr during euglycemic hyperinsulinemic clamp: change from baseline

  4 weeks

Secondary Outcomes (8)

• Effect on Coronary flow reserve [Main Secondary Outcome]

  4 weeks

• 3. Browning of white adipose tissue: change from baseline

  4 weeks

• Metabolic systemic effects of dapagliflozin

  4 weeks

• Effect on Left Ventricular Ejection Fraction at rest

  4 weeks

• Effect on Left Ventricular Ejection Fraction during pharmacological stress

  4 weeks

Study Arms (2)

A - placebo

PLACEBO COMPARATOR

Green, plain, diamond shaped, film coated tablet (orally), not containing active ingredient; once daily, for 4 weeks

Other: Placebo

B - experimental drug

EXPERIMENTAL

Dapagliflozin tablet available at dose of 10 mg, once daily, for 4 weeks

Drug: Dapagliflozin 10Mg Tab

Interventions

Dapagliflozin 10Mg Tab DRUG

Dapagliflozin, will be administered according to the approved posology and to the approved dose as stated by Local Health Indication and by the Drug Brochure

B - experimental drug

Placebo OTHER

placebo

A - placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study-specific procedures
• Female or male subjects aged between 40 and 75 inclusive. Patients who have been surgically sterilized (hysterectomy or tubal-ligation) at least 12 months prior to screening, or are postmenopausal having had no regular menstrual bleeding for at least one (1) year prior to screening. Menopause will be confirmed by a plasma follicle stimulating hormone (FSH) level of \> 35 IU/mL at screening, or Women with childbearing potential willing not to initiate pregnancy during the course of the study, and non-nursing women.
• Men having relationships with women with childbearing potential willing not to procure a pregnancy during the course of the study;
• Patients with type 2 diabetes
• Patients with established, stable CAD, defined as ≥30% coronary stenosis in at least one major coronary vessel on invasive coronary angiography (ICA) or computed tomography angiography (CTA) performed within 12 months from screening and no indication to revascularization or with no evidence of critical restenosis, if previously subjected to percutaneous coronary intervention (PCI) (\>6months).
• Patients with a clinical indication for 13N-ammonia PET-CT, as established by a cardiologist, nuclear medicine physician or diabetologist.
• Patients with a body mass index (BMI) equal or greater than 25 kg/m2 but less than 35 kg/m2 \[BMI = Weight (kg) / Height squared (m2)\]
• Patients with a HbA1c between 7.0% and 8.5%, according to the actual clinical conditions of the patients;
• Patients with diabetes duration \<10 years;

You may not qualify if:

• Patients with Fasting C-peptide \> 1 ng/mL (0.33 nmol/L) at Visit 0
• History of diabetic ketoacidosis or hyperosmolar non-ketotic coma
• NYHA class III or IV
• Unstable angina
• Previous re-vascularisation (either percutaneous coronary intervention or coronary artery bypass graft) in the last \<6 months before screening
• Reduced left ventricular ejection fraction (≤ 50%)
• Increased likelihood of developing diabetic ketoacidosis (history of DKA, alcohol consumption, volume depletion dehydration, clinical conditions causing diarrhea, vomit and anorexia)
• Moderate to severe renal impairment (eGFR\<60 ml/min/1.73m2 as calculated by the modification of diet in renal disease \[MDRD\] equation or end-stage renal disease); overt proteinuria, defined as Spot urine Microalbumin/Cr ratio of \>300 mg/g at screening (Visit 0)
• Severe liver dysfunction
• Asthma
• Uncontrolled blood pressure
• Symptomatic tachy- or bradyarrhythmias
• Previous acute myocardial infarction
• Contraindications to adenosine: known hypersensitivity to adenosine or to any of the excipients; sick sinus syndrome, second or third degree atrio-ventricular block (except in patients with a functioning artificial pacemaker); chronic obstructive lung disease with evidence of bronchospasm (e.g. bronchial asthma ); long QT syndrome; severe hypotension; decompensated states of heart failure
• Use of pioglitazone; use of loop diuretics; basal-bolus insulin therapy; use of systemic steroids less than 3 days prior to the screening visit (Visit 0)

Sponsors & Collaborators

• Giaccari Andrea: lead

Study Sites (1)

Center For Endocrine and Metabolic Diseases - Catholic University

Rome, RM, 00168, Italy

Location

Related Publications (4)

• Cinti F, Leccisotti L, Sorice GP, Capece U, D'Amario D, Lorusso M, Gugliandolo S, Morciano C, Guarneri A, Guzzardi MA, Mezza T, Capotosti A, Indovina L, Ferraro PM, Iozzo P, Crea F, Giordano A, Giaccari A. Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes. Cardiovasc Diabetol. 2023 Dec 19;22(1):349. doi: 10.1186/s12933-023-02091-0.

  PMID: 38115004 DERIVED

• Capece U, Pavanello C, Cinti F, Leccisotti L, Mezza T, Ciccarelli G, Moffa S, Di Giuseppe G, Soldovieri L, Brunetti M, Giordano A, Giaccari A, Calabresi L, Ossoli A. Dapagliflozin-Induced Myocardial Flow Reserve Improvement is not Associated with HDL Ability to Stimulate Endothelial Nitric Oxide Production. Diabetes Ther. 2024 Jan;15(1):257-268. doi: 10.1007/s13300-023-01491-5. Epub 2023 Oct 26.

  PMID: 37883003 DERIVED

• Leccisotti L, Cinti F, Sorice GP, D'Amario D, Lorusso M, Guzzardi MA, Mezza T, Gugliandolo S, Cocchi C, Capece U, Indovina L, Ferraro PM, Iozzo P, Crea F, Giordano A, Giaccari A. Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report. Cardiovasc Diabetol. 2022 Sep 3;21(1):173. doi: 10.1186/s12933-022-01607-4.

  PMID: 36057768 DERIVED

• Sorice GP, Cinti F, Leccisotti L, D'Amario D, Lorusso M, Guzzardi MA, Mezza T, Cocchi C, Capece U, Ferraro PM, Crea F, Giordano A, Iozzo P, Giaccari A. Effect of Dapagliflozin on Myocardial Insulin Sensitivity and Perfusion: Rationale and Design of The DAPAHEART Trial. Diabetes Ther. 2021 Jul;12(7):2101-2113. doi: 10.1007/s13300-021-01083-1. Epub 2021 May 26.

  PMID: 34037951 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

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

Study Officials

• Andrea Giaccari

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 4, 2017
• First Posted: October 18, 2017
• Study Start: December 1, 2017
• Primary Completion: October 6, 2022
• Study Completion: October 6, 2022
• Last Updated: May 8, 2026

Record last verified: 2026-05

Locations

IT (1)