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Type2 Diabetes MellitusPhase 3DapaHeartNCT03313752

Effects of SGLT2 Inhibition on Myocardial Insulin Sensitivity

A Phase 3 study testing Dapagliflozin 10Mg Tab in people with Type2 Diabetes Mellitus and Stable Coronary Artery Disease, run by Giaccari Andrea at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 40 to 75 years
What is being tested?
Dapagliflozin 10Mg Tab
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
25 participants
Where
1 siteItaly
Study dates
1 Dec 2017to 6 Oct 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 11Show fewer
  • 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;
  • Patients with stable medical therapy [including other anti-hyperglycemic agents (see Table 1, section 5.2.1 for all therapies allowed, as per current standard treatment); pioglitazone and basal-bolus insulin treatment are excluded, as reported in the exclusion criteria 15] for at least 3 months prior to the screening visit (including stable insulin dose defined as no variation more than 30% in daily insulin dose within the preceding 3 months.
  • Patients with Fasting C-peptide > 1 ng/mL (0.33 nmol/L) at Visit 0

Who cannot join

  • Type 1 diabetes (as assessed by medical history); previous diagnosis of Latent Autoimmune Diabetes of Adults (LADA), and or not fulfilling inclusion criteria #10
  • 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%)
Show all 23Show fewer
  • 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)
  • Known hypersensitivity to the active substance or to any of the excipients in study drug
  • Inability to provide informed consent
  • Participation in another clinical study with an investigational product during the previous 30 days
  • Patients with history of breast, bladder and prostate cancer
  • Patients who will undergo surgical procedures
  • Patients with acute urinary tract infection
  • Patients with history of intolerance to galactose and lactose
  • Severe/uncontrolled medical conditions, causing liquid volume depletion

Trial locations and contacts

1 site in 1 country.

Italy1 site
  • Center For Endocrine and Metabolic Diseases - Catholic University

    Rome, RM, 00168

Other trials in Italy

About this study

Official title: Study on the Effect of Dapagliflozin on Myocardial Insulin Sensitivity and Perfusion

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

Read more

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).

Read the detailed description

This Phase III, single-centre, randomized, double-blind, placebo-controlled study is designed to evaluate the impact of dapagliflozin on myocardial insulin sensitivity, global cardiac function, metabolic effects, and glycemic control in patients with type 2 diabetes (T2D) and stable coronary artery disease (CAD). The study consists of three phases: a 14-day screening phase (Days -14 to -1), a 4-week double-blind treatment phase, and a 4-week follow-up phase.

Patients eligible for this study must have suboptimal glycemic control (HbA1c 7.0-8.5%) on a stable anti-hyperglycemic regimen and meet specific inclusion criteria, including a history of stable CAD with ≥30% coronary stenosis or prior percutaneous coronary intervention (PCI) performed at least six months prior to screening, without an indication for revascularization. These patients should have undergone a routine 13N-ammonia PET-CT scan to assess cardiovascular function before enrollment.

During the study, participants are randomized in a 1:1 ratio to receive either 10 mg dapagliflozin or a placebo tablet, administered orally once daily for four weeks. Key assessments include a euglycemic hyperinsulinemic clamp to measure myocardial glucose uptake (MGU) and systemic glucose metabolism. The primary outcome focuses on the change in MGU, reflecting myocardial insulin sensitivity, while secondary outcomes evaluate:

Coronary flow reserve (CFR): Determined as the ratio of myocardial blood flow (MBF) during pharmacological stress to MBF at rest, measured using PET-CT.

Left ventricular function: Assessed at rest and during pharmacological stress via Gated-PET with 13N-ammonia.

Metabolic effects on adipose tissue: Quantitative FDG uptake in pericardial, perirenal, and interscapular fat, measured as SUVmax.

Glycemic control: Changes in fasting glucose concentration and glycated hemoglobin (HbA1c).

Gut microbiota composition: Analyzed at the class, genus, and species levels to assess systemic metabolic effects.

The study aims to enroll patients aged 40-75 years, with a body mass index (BMI) between 25 and 35 kg/m² and a diabetes duration of less than 10 years. Patients with type 1 diabetes, recent myocardial infarction, severe renal or hepatic impairment, or contraindications to study procedures or medications are excluded.

At the end of 4 week-trial, all the patients in the placebo group will start therapy with dapagliflozin.

All the patients will be followed up every 4 years. Coronary flow reserve (CFR): Determined as the ratio of myocardial blood flow (MBF) during pharmacological stress to MBF at rest, measured using PET-CT, will be re-evaluated at the end follow up.

This trial seeks to determine whether the metabolic and cardiac improvements achieved with dapagliflozin are superior to those achieved with standard clinical practice, aligning with current Standards of Care. The results will provide robust evidence on the role of SGLT2 inhibitors in addressing the residual cardiovascular risk in T2D patients.

Being tested
Dapagliflozin 10Mg Tab, Placebo
Keywords
diabetes, heart, dapagliflozin,
Medical subject headings
Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dapagliflozin 10Mg TabDrug

    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

  • PlaceboOther

    placebo

Study groups in NCT03313752
Study groupRoleWhat they receive
A - placeboPlacebo comparatorGreen, plain, diamond shaped, film coated tablet (orally), not containing active ingredient; once daily, for 4 weeks
Receives: Other: Placebo
B - experimental drugExperimentalDapagliflozin tablet available at dose of 10 mg, once daily, for 4 weeks
Receives: Drug: Dapagliflozin 10Mg Tab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Effect of dapagliflozin on myocardial insulin sensitivity

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

    Measured: 4 weeks

Secondary outcomes (8)
  1. Effect on Coronary flow reserve [Main Secondary Outcome]

    Coronary flow reserve (CFR) obtained as ratio of myocardial blood flow (ml/min/g) (MBF) during pharmacological stress and MBF at rest: change from baseline

    Measured: 4 weeks

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

    Quantitative measurement of FDG uptake in pericardial, perirenal, interscapular fat by total body FDG PET-CT study, expressed as maximum Standard Uptake Volume (SUVmax) (change from baseline)

    Measured: 4 weeks

  3. Metabolic systemic effects of dapagliflozin

    Whole body glucose uptake calculated as mg/kg/min during the euglycemic hyperinsulinemic clamp: change from baseline

    Measured: 4 weeks

  4. Effect on Left Ventricular Ejection Fraction at rest

    Whole body glucose uptake calculated as mg/kg/min during the euglycemic hyperinsulinemic clamp: change from baseline

    Measured: 4 weeks

  5. Effect on Left Ventricular Ejection Fraction during pharmacological stress

    Left Ventricular Ejection Fraction (percent %) measured by Gated-PET with 13N-ammonia during pharmacological stress: change from baseline

    Measured: 4 weeks

  6. Fasting glucose concentration change from baseline

    Measured as fasting glucose concentration (mg/dl): change from baseline

    Measured: 4 weeks

  7. Glycemic control change from baseline

    Measured as Glycated hemoglobin (HbA1c) (percent %): change from baseline

    Measured: 4 weeks

  8. Gut microbiota composition change from baseline

    Analysis of gut microbiota composition at class, genus, and species levels: change from baseline

    Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Oct 2017
  2. Study start1 Dec 2017
  3. Primary completion6 Oct 2022
  4. Study completion6 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Care provider
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03313752
Sponsor's protocol ID
2016-003614-27
Other IDs
2016
Acronym
DapaHeart
Status last verified
May 2026
First submitted
4 Oct 2017
Last updated
8 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Cinti F, Morciano C, Guarneri A, Cappannoli L, Sorice G, Gugliandolo S, Capece U, Splendore A, Avolio A, Mezza T, Iozzo P, Pontecorvi A, Calcagni ML, Burzotta F, D'Amario D, Crea F, Leccisotti L, Giaccari A. Coronary flow reserve increase after 4-year dapagliflozin treatment in patients with type 2 diabetes: the DAPAHEART follow-up study. Cardiovasc Diabetol. 2025 Aug 31;24(1):351. doi: 10.1186/s12933-025-02912-4.

    PubMed 40887630
  • 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.

    PubMed 38115004
  • 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.

    PubMed 37883003
  • 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.

    PubMed 36057768
  • 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.

    PubMed 34037951

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dapagliflozin 10Mg Tab in people with Type2 Diabetes Mellitus and Stable Coronary Artery Disease, run by Giaccari Andrea at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of dapagliflozin on myocardial insulin sensitivity (time frame: 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03313752, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.

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