Dapagliflozin vs Empagliflozin on Flow Mediated Dilation in Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Type 2 diabetes mellitus (T2DM) is a considered one of the main global health challenges; the vascular endothelium plays an important role in vascular dysfunction in DM; Hyperglycemia induced by it is recognized as the main factor for the development of vascular complications of the disease, secondary to a reduction in nitric oxide production; flow-mediated dilation is the most commonly used technique for the evaluation of endothelial function, being the non-invasive method most widely used. It has been reported that with the use of SGLT2 inhibitors the development of cardiovascular complications in patients with T2DM is a decrease, as well the arterial stiffness, endothelial dysfunction and increasing on the shear stress and blood viscosity; and experimentally.

Detailed Description
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The objective of this study, is to evaluate the acute effect of the administration of dapagliflozin in comparison with the administration of empagliflozin on endothelial disfunction in individuals with T2DM; we will conduct a double-blind, randomized, placebo-controlled, trial with 3 groups, each group of 24 male and female patients, between 40-65 years of age with T2DM, without hypertension, treated with insulins or thiazide diuretics. Randomization will determine who will receive the intervention during 7-days trial (Empagliflozin 25 mg 1 time daily 5 minutes or Dapagliflozin 10 mg before the first bite of each meal or approved placebo capsules), the patients will also continue with their usual treatment. The clinical findings and laboratory test and laboratory test include a metabolic profile and biosafety, baseline and at 7 days. Body weight, body fat, body mass index (BMI) and blood pressure will be determined during the initial and final visit, likewise, hemodynamics parameters of endothelial disfunction by flow mediate dilation with a high-resolution UNEX EF38G® ultrasound. Adverse events to treatment will be documented. Statistical analysis: Mann-Whitney U Test and Wilcoxon exact test. A p <0.05 will be considered statistically significant.

Official Title
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Acute Effect of Dapagliflozin vs Empagliflozin Administration on Flow Mediated Dilation in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin Pill
* Drug: Empagliflozin Pill
* Drug: Placebo pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of T2DM HbA1c > 7 y < 10 BMI 25 - 34.9 kg/m2 Signature of consent under information Exclusion Criteria: Hypertension Treated with insulin and / or loop diuretics and thiazides T1DM Hypotension With any autoimmune disease Liver disease Women who do not have a safe method of contraception Women who are taking oral contraceptives or under treatment with hormone replacement therapy Woman pregnant or breastfeeding Untreated thyroid disease Patients with a cardiovascular disease that contraindicates the use of this pharmacological class Glomerular filtration rate <60ml/min (Cockcroft-Gault)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>Individuals with T2DM controlled with metformin; with no hypertension neither treated with insulin. Dapagliflozin capsules, 10 mg 1 time daily 5 minutes before the first meal | Drug: Dapagliflozin Pill<br>* The patient will take one pill, every 24 hr, during 7 days<br>* Other names: Dapagliflozin;|
| Experimental: Empagliflozin<br>Individuals with T2DM controlled with metformin; with no hypertension neither treated with insulin. Empagliflozin capsules, 25 mg 1 time daily 5 minutes before the first meal | Drug: Empagliflozin Pill<br>* The patient will take one pill, every 24 hr, during 7 days<br>* Other names: Empagliflozin;|
| Placebo Comparator: Placebo<br>Individuals with T2DM controlled with metformin; with no hypertension neither treated with insulin. Dapagliflozin capsules, 400 mg 1 time daily 5 minutes before the first meal | Drug: Placebo pill<br>* The patient will take one pill, every 24 hr, during 7 days<br>* Other names: Calcined magnesia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow Mediated Dilation | Change from baseline Flow mediated dilation at 7 days. Using a high-resolution UNEX EF38G ultrasound®, in a room at 22°C, with the patient lying supine, and the right arm extended | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting plasma glucose | Before and after intervention, using the BioSystems® Glucose Oxidase / Peroxidase kit; in an automated clinical chemistry analysis equipment brand XL-100Erba | 7 days | 
| Total cholesterol | Before and after intervention, using the BioSystems® Glucose Oxidase / Peroxidase kit. | 7 days | 
| Triglycerides | Before and after intervention, using the BioSystems® Glycerol phosphate Oxidase / Peroxidase kit. | 7 days | 
| High-density lipoprotein cholesterol | Before and after intervention, using the BioSystems® Direct / Detergent HDL kit | 7 days | 
| Low-density lipoprotein cholesterol | Before and after intervention using the BioSystems® Cholesterol Oxidase / Peroxidase kit | 7 days | 
| Creatinine | Before and after intervention the BioSystems® kit Modified Jaffe's no deproteinization | 7 days | 
| Blood pressure | Before and after intervention using an OMRON calibrated electronic digital sphygmomanometer model HEM 907 XL will be used. The patient will remain seated in a chair resting his back on the backrest, with a minimum rest of 5 minutes, The average of 3 measurements such as BP will be taken | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FMD, Dapagliflozin, Empagliflozin, T2DM, Endothelial disfunction