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

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

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.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Dapagliflozin Pill; Drug: Empagliflozin Pill; Drug: Placebo pill

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dapagliflozin; 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; The patient will take one pill, every 24 hr, during 7 days; Other Names: Forxiga; Dapagliflozin
EXPERIMENTAL: Empagliflozin; 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; The patient will take one pill, every 24 hr, during 7 days; Other Names: Jardiance; Empagliflozin
PLACEBO_COMPARATOR: Placebo; 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; The patient will take one pill, every 24 hr, during 7 days; Other Names: Calcined magnesia

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centro Universitario de Ciencias de la Salud, Mexico
• Investigators: Study Director: Fernando Grover Paez, PhD, Institute of Experimental and Clinical Therapeutics (INTEC), CUCS

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 2, 2019
• Primary Completion (ANTICIPATED): June 29, 2020
• Study Completion (ANTICIPATED): December 30, 2020

Study Registration Dates

• First Submitted: December 4, 2019
• First Submitted That Met QC Criteria: December 10, 2019
• First Posted (ACTUAL): December 11, 2019

Study Record Updates

• Last Update Posted (ACTUAL): December 11, 2019
• Last Update Submitted That Met QC Criteria: December 10, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Dapagliflozin; Empagliflozin; T2DM; FMD; Endothelial disfunction
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Empagliflozin
• Other Study ID Numbers: CUCS-INTEC-MV-HADES-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No