Acute and Short-term Chronic Effects of Galvus (Vildagliptin) in Diabetes Type 2 Obese Women

Acute and Short-term Chronic Effects of Galvus (Vildagliptin) on Endothelial Function and Oxidative Stress on Recently Diagnosed Type 2 Diabetic Obese Women: the Role of Intestinal Peptides During Lipid Overload

The prevalence of obesity and type 2 diabetes mellitus (T2DM) has increased progressively in the past decades, and consequently, a higher incidence of cardiovascular diseases is observed. As this process develops, the endothelial dysfunction is present at early stages of the atherosclerotic disease. Studies conducted at BioVasc/UERJ show the occurrence of endothelial and microvascular dysfunction in obese carriers, even in the absence of dysglycemia. New concepts indicate the endothelium as a possible therapeutic target, and drugs which act not only on diabetes mellitus pathophysiology but also acting as direct cardiovascular protectors bring new therapeutic possibilities. The dipeptidyl-peptidase-4 inhibitors (DPP4), such as vildagliptin, are drugs used on the T2DM treatment. Its incretin mimetic and insulinotropic effects are already well established and several other studies show its effectiveness in reducing glycated hemoglobin, even in monotherapy.

Currently, fat rich foods are being increasingly introduced in the western way of life and recent evidence suggests that the postprandial lipemia (LPP) is related to cardiovascular risk. A better glucose control using vildagliptin can reduce the oxidative stress, and consequently promote a better microvascular and endothelial reactivity. However, vildagliptin can have an additional cardiovascular protective action, not only because of its effect on glycemia and oxidative stress reduction, but maybe because of its direct effect on intestinal peptides with postprandial lipemia reduction. To test this hypothesis, we will proceed the following exams: venous occlusion pletysmography, nailfold videocapilaroscopy and laser-Doppler flowmetry aiming to evaluate vascular reactivity on muscle and at cutaneous site. Anoter group of patients with the same clinical charactherisitics will use metformin, in order to compare its effects with those obtained from the use of Vildaglitpin. Our purpose is to determine whether vildagliptin, evaluated in obese and diabetic women, has vascular protective effects, and whether the regulatory mechanisms of these actions correlate with oxidative stress, inflammatory markers and intestinal peptides in baseline state and after a lipid overload.

Study Overview

• Status: Completed
• Conditions: 1- Microvascular Function; 2-oxidative Stress; 3-inflammation
• Intervention / Treatment: Drug: Vildagliptin

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20550-900
    • Laboratory for Clinical and Experimental Research on Vascular Biology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• All patients should have BMI > 30kg/m²
• Present untreated diabetes mellitus type 2
• Age between 19 and 50 years
• Waist Circumference > 80 cm

Exclusion Criteria:

• Renal, coronary vascular or peripheral, hematologic or hepatic disease
• Presence of severe hypertriglyceridemia (> 400mg/dl)
• Smokers
• Significant body mass loss (> 5%) within the six months prior to the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin; Metformin 850mg/pill will be administered at lunch time and dinner time for 30 days	Drug: Vildagliptin; Vildagliptin 50mg/pill will be administered at 10 AM and at 6 PM also for 30 days.; Other Names: Vildagliptin (galvus)
Experimental: Vildagliptina; Vildagliptin 50mg/pill will be administered at 10 AM and at 6 PM also for 30 days.	Drug: Vildagliptin; Vildagliptin 50mg/pill will be administered at 10 AM and at 6 PM also for 30 days.; Other Names: Vildagliptin (galvus)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in microcirculation function at 30 days	For this study, there will be used two methods, the traditional one, which consists in assessing the microcirculation parameters by dynamic nailfold videocapillaroscopy technique carried out in the nailfold pleat of the fourth finger on the left hand.	Before and after 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in endothelial function at 30 days	LDF is a method for continuous non invasive determination of the microvascular perfusion, where the study of cutaneous vasomotion by spectral analysis of Laser Doppler signal allows the exploration of five frequency components: endothelial, myogenic, sympathetic, respiratory and cardiac, involved in answers to the stimuli. Therewith vasomotion during the whole study period will be assessed, to find differences in baseline, 30, 60, 120 and 180 min after the meal rich in lipids.	before and after 30 days (intervention)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in incretins and inflammation markers at 30 days	Through kits read by Multiplex® appliance, inflammatory markers will be evaluated, all simultaneously, with small sample quantity (from 10 to 50µL).	basal and after 30 days (intervention)

Collaborators and Investigators

• Sponsor: Rio de Janeiro State University
• Collaborators: Laboratory for Clinical and Experimental Research on Vascular Biology

Publications and helpful links

General Publications

• Schiapaccassa A, Maranhao PA, de Souza MDGC, Panazzolo DG, Nogueira Neto JF, Bouskela E, Kraemer-Aguiar LG. 30-days effects of vildagliptin on vascular function, plasma viscosity, inflammation, oxidative stress, and intestinal peptides on drug-naive women with diabetes and obesity: a randomized head-to-head metformin-controlled study. Diabetol Metab Syndr. 2019 Aug 23;11:70. doi: 10.1186/s13098-019-0466-2. eCollection 2019.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2013
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: April 2, 2013
• First Submitted That Met QC Criteria: April 4, 2013
• First Posted (Estimate): April 9, 2013

Study Record Updates

• Last Update Posted (Actual): May 31, 2017
• Last Update Submitted That Met QC Criteria: May 30, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: incretins; diabetes mellitus; endothelial function; microvascular function; postprandial lipemia
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Vildagliptin
• Other Study ID Numbers: Galvus_2013; BioVasc_2013 (Registry Identifier: BioVasc_2013)