Clinical trial NCT03377335: Dapagliflozin, Cardio-Metabolic Risk Factors and Type-2 Diabetes
Official title: Effect of Dapagliflozin on Cardio-Metabolic Risk Factors in Patients With Type-2 Diabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Dapagliflozin
Type 2 diabetes mellitus
Carotid intima-media thickness
Endothelial dysfunction
Atherogenic lipoproteins
Inflammatory markers
microRNAs
Lead sponsor: University of Palermo
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: University of Catania
First posted: 2017-12-19
Enrollment: 186
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Subclinical atherosclerosis
timeFrame: Change from baseline to 6 months of the treatment
Secondary outcomes:
measure: Endothelial dysfunction
timeFrame: Change from baseline to 6 months of the treatment
measure: Oxidative stress
timeFrame: Change from baseline to 6 months of the treatment
measure: Atherogenic lipoproteins
timeFrame: Change from baseline to 6 months of the treatment
measure: Inflammatory markers
timeFrame: Change from baseline to 6 months of the treatment
measure: microRNAs
timeFrame: Change from baseline to 6 months of the treatment
Other outcomes:
Locations:
city: Palermo
country: Italy
facility: University Hospital of Palermo
Study officials:
References:
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