Dapagliflozin, Cardio-Metabolic Risk Factors and Type-2 Diabetes

NCT ID: NCT03377335

Last Updated: 2018-02-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 186 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-22
• Study Completion Date: 2019-01-31

Brief Summary

Dapagliflozin is a member of the sodium-glucose cotransporter-2 (SGLT2) inhibitor class antidiabetes agents which produces significant and sustained reductions in glycemic parameters in patients with type 2 diabetes (T2DM). However, its non-glycemic effects are still largely unknown.

The investigators will evaluate for the first time the effect of dapagliflozin on multiple cardio-metabolic risk markers in one study. So far, no data on the effects of dapagliflozin as well as other SGLT-2 inhibitors on subclinical atherosclerosis, endothelial function, inflammatory markers, cytokines and atherogenic lipoproteins is available.

In addition, the investigators will examine microRNAs (miRNAs) implicated in the development and progression of atherosclerotic disease. Again, no data is currently available on dapaglifozin's as well as other SGLT-2 inhibitors' effects on miRNAs.

The results of this study will show for the first time the potential multiple, non-glycemic effects of dapagliflozin, reducing multiple cardio-metabolic risk markers, which will ultimately lead to decreased CV risk.

In addition, specific mechanisms of the dapagliflozin cardiovascular action will be investigated.

Finally, the results of this study may pave the way for personalized therapy (using the results on miRNAs).

Detailed Description

The investigators will perform an open label, two-arms, prospective intervention study using dapagliflozin+metformin vs. metformin alone for a period of 6 months in patients with T2DM.

The research hypothesis is to assess whether dapagliflozin can improve cardio-metabolic outcome, reducing subclinical atherosclerosis, endothelial dysfunction and different cardio-metabolic markers (including inflammatory markers, cytokines, oxidative stress and atherogenic lipoproteins) in patients with T2DM.

The primary objective is to assess the effects of dapagliflozin on subclinical atherosclerosis, as assessed by carotid intima-media thickness (cIMT).

Primary endpoint: Reduction in cIMT.

The secondary objective is to assess the effects of dapagliflozin on glycemic parameters (fasting plasma glucose (FPG), HbA1c), endothelial dysfunction, oxidative stress, atherogenic lipoproteins, inflammatory markers, cytokines and microRNAs (miR-130a, miR-27b, miR-29b and miR-210).

Secondary endpoint: Reduction in glycemic parameters, atherogenic lipoproteins, inflammatory markers, oxidative stress and improvements in endothelial function, cytokines and microRNAs (miR-130a, miR-27b, miR-29b and miR-210).

The full data for clinical and biochemical analyses will be collected in the same fashion at baseline and after 6 months of therapy.

Control visits by the telephone calls will be made every 2 months. However, in case of need, unplanned visits will be scheduled. Unscheduled visits will be performed in case of discontinuation, withdrawal, rescue treatment (including adverse event, episodes of hypoglycemia) or at any time during the study in case of patient's need.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dapagliflozin

Dapagliflozin (10mg daily) as add-on to metformin (stable doses ranging from 1500 to 3000 mg daily).

The total duration of treatment is 6 months.

Group Type: EXPERIMENTAL

Dapagliflozin 10mg

Intervention Type: DRUG

The subjects in this arm will receive dapagliflozin (10mg daily) as add-on to metformin therapy (doses ranging from 1500 to 3000 mg daily).

Number of patients to be randomized: 93

Number of patients expected to complete the study: >87

All the other medications (including lipid-lowering, anti-hypertensive and anti-platelet agents) will be maintained at fixed doses during the treatment.

Metformin alone

Metformin alone (stable doses ranging from 1500 to 3000 mg daily).

The total duration of treatment is 6 months.

Group Type: PLACEBO_COMPARATOR

Metformin

Intervention Type: DRUG

All the subjects in this arm will be on metformin therapy only (doses ranging from 1500 to 3000 mg daily).

Number of patients to be randomized: 93

Number of patients expected to complete the study: >87

All the other medications (including lipid-lowering, anti-hypertensive and anti-platelet agents) will be maintained at fixed doses during the treatment.

Interventions

Dapagliflozin 10mg

The subjects in this arm will receive dapagliflozin (10mg daily) as add-on to metformin therapy (doses ranging from 1500 to 3000 mg daily).

Number of patients to be randomized: 93

Number of patients expected to complete the study: >87

All the other medications (including lipid-lowering, anti-hypertensive and anti-platelet agents) will be maintained at fixed doses during the treatment.

Intervention Type: DRUG

Metformin

All the subjects in this arm will be on metformin therapy only (doses ranging from 1500 to 3000 mg daily).

Number of patients to be randomized: 93

Number of patients expected to complete the study: >87

All the other medications (including lipid-lowering, anti-hypertensive and anti-platelet agents) will be maintained at fixed doses during the treatment.

Intervention Type: DRUG

Other Intervention Names

Forxiga®; Glucophage®

Eligibility Criteria

Inclusion Criteria

• men and women with T2DM;
• age >18;
• BMI ≥20 kg/m^2;
• HbA1c 7.0-9.0 %;
• receiving metformin therapy at least 1500 mg/day for at least 8 weeks before screening;
• plasma triglycerides <400 mg/dL, plasma LDL-cholesterol < 250 mg/dL;
• stabile daily dose(s) of hypolipidemic drugs (statins, ezetimibe) for at least 7 weeks prior to the day of randomization;
• adequately controlled blood pressure (≤140/90 mmHg) to be maintained during the study according to Standard of Care;
• able to swallow whole tablets.

Exclusion Criteria

• pregnancy or willingness to became pregnant;
• severe liver dysfunction (alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 3 times upper limit of normal);
• renal failure with glomerular filtration rate (eGFR) <60 ml/min/1.73m^2;
• major cardiovascular event (myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischaemic attack) within 12 weeks before screening;
• severe infections (such as HIV and HCV);
• any malignancy within 5 years before screening.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

University of Catania

OTHER

Sponsor Role: collaborator

University of Palermo

OTHER

Sponsor Role: lead

Responsible Party

Manfredi Rizzo

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Hospital of Palermo

Palermo, , Italy

Countries

Italy

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Other Identifiers

ESR-16-12388

Identifier Type: -

Identifier Source: org_study_id