Clinical trial NCT01827280: Acute and Short-term Chronic Effects of Galvus (Vildagliptin) in Diabetes Type 2 Obese Women
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: 1- Microvascular Function
2-oxidative Stress
3-inflammation
Keywords: endothelial function
microvascular function
incretins
diabetes mellitus
postprandial lipemia
Lead sponsor: Rio de Janeiro State University
Sponsor class: OTHER
Collaborators: name: Laboratory for Clinical and Experimental Research on Vascular Biology
First posted: 2013-04-09
Enrollment: 40
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change from Baseline in microcirculation function at 30 days
timeFrame: Before and after 30 days
Secondary outcomes:
measure: Change from Baseline in endothelial function at 30 days
timeFrame: before and after 30 days (intervention)
Other outcomes:
measure: Change from Baseline in incretins and inflammation markers at 30 days
timeFrame: basal and after 30 days (intervention)
Locations:
city: Rio de Janeiro
country: Brazil
facility: Laboratory for Clinical and Experimental Research on Vascular Biology
Study officials:
References:
citation: 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.