Clinical trial NCT03444142: Effect of Exenatide LAR or Dulaglutide on the Variability of 24-hour Heart Rate and Blood Pressure in Type 2 Diabetes
Official title: Effect of the Weekly Administration of Exenatide LAR or Dulaglutide on the Variability of Blood Pressure and Heart Rate of 24 Hours in Patients With Type 2 Diabetes Mellitus Without Pharmacological Treatment.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes
Hyperglycemia
ABPM
Variability of blood pressure
Exenatide LAR or Dulaglutide 0.75mg
Glucagon-like peptide analogues type 1 (GLP1).
Lead sponsor: University of Guadalajara
Sponsor class: OTHER
First posted: 2018-02-23
Enrollment: 30
Sex: ALL
Minimum age (years): 31
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Mortality due to cardiovascular problems is increased by having Diabetes Mellitus type 2 (DM2), related to the time of evolution and glucose levels or if alterations in blood pressure coexist. With this variability there is greater damage to the target organ and in patients with DM2 the process is more severe and frequent due to alterations in the coagulation mechanisms that accelerate in the presence of hypertension, figures ≥135 / 85 mmHg are considered risk factors to develop coronary, cerebral or renal events. As a quantitative range, blood pressure is currently monitored ambulatory by (MAP) which is the most used and reliable non-invasive instrument for its evaluation. The American Association of Clinical Endocrinologists (AACE) proposes an algorithm that contemplates initiating management to patients with a diagnosis of diabetes with drugs such as metformin, thiazolidinediones and glucagon-like peptide analogues type 1 (GLP1).

Exenatide LAR and Dulaglutide are GLP-1 analogue drugs with potential to decrease the progressive losses of pancreatic β cell function and mass and cardiovascular risk (CV) factors with maintained use, in addition to hypoglycemic, hypotensive effects, weight decreases and visceral adiposity, however, it has been reported that although they share the same basic mechanism of action, each one has a different molecular structure and pharmacokinetic profile that make their pharmacological and clinical effects different, in particular as regards the variability of blood pressure and heart rate.

Detailed description: A randomized, open clinical trial of 30 patients with a diagnosis of diabetes in accordance with the American Diabetes Association (ADA) without treatment.

They will be assigned randomly in two groups of 15 patients each to receive 2 mg subcutaneous of Exenatide LAR (Bydureon by Astra Zeneca) or Dulaglutide .75 mg (trulicity, by Lilly), once weekly before breakfast during 4 weeks.

There will be calculated body mass index (BMI); low-density lipoprotein cholesterol (LDL-c); very-low density lipoprotein (VLDL), glomerular filtration rate and blood pressure variability. This protocol it's already approved by the local ethics committee with number CEI/447/2017 and written informed consent it's going to be obtained from all volunteers.

Statistical analysis will be presented through measures of central tendency, dispersion, average and deviation standard for quantitative variables, frequencies and percentages for variable qualitative. Qualitative variables will be analyzed by X2, will be used for differences inter-group Mann-Whitney U Test and Wilcoxon Test for the within-groups differences. It will be considered statistical significance p ≤0.05.

Eligibility criteria: Inclusion Criteria:

* Patients both sexes
* Age between 31 and 60 years
* Diagnosis of diabetes according ADA criteria:

(Fasting blood glucose levels \>125 mg/dl or postprandial blood glucose levels after an oral glucose tolerance test with 75 of oral glucose \> 200 mg/dl, or glycosylated hemoglobin \>6.5%).

• Informed consent signed

Exclusion Criteria:

* Women with confirmed or suspected pregnancy
* Women under lactation and/or puerperium
* Hypersensibility to ingredients of intervention
* Physical impossibility for apply the drug
* Known pancreatic, renal, hepatic, heart or thyroid diseased
* Hypertension diagnosis
* Previous treatment for glucose
* Body Mass Index ≥39.9 kg/m2
* Triglycerides ≥500 mg/dL
* Total cholesterol ≥300 mg/dL
* Night or rotating shift workers
* Blood Pressure ≥140/90 mmHg

Primary outcomes:
measure: Heart rate: nighttime, daytime and 24-h
timeFrame: Baseline to Week 4
measure: Systolic blood pressure, daytime, night and 24 h
timeFrame: Baseline to Week 4
measure: Diastolic blood pressure, daytime, night and 24 h
timeFrame: Baseline to Week 4
measure: Blood pressure
timeFrame: Baseline to Week 4
Secondary outcomes:
measure: Categories: dipper o non dipper
timeFrame: Baseline to Week 4
measure: Fasting glucose levels
timeFrame: Baseline to Week 4
measure: Central and peripheral blood pressure
timeFrame: Baseline to Week 4
measure: Pulse wave velocity
timeFrame: Baseline to Week 4
measure: Cardio-ankle Vascular Index (CAVI)
timeFrame: Baseline to Week 4
measure: Glycosylated hemoglobin
timeFrame: Baseline to Week 4
measure: Body Weight
timeFrame: Baseline to Week 4
measure: Body Mass Index
timeFrame: Baseline to Week 4
measure: Total cholesterol
timeFrame: Baseline to Week 4
measure: Triglycerides levels
timeFrame: Baseline to Week 4
measure: High density lipoprotein (c-HDL) levels
timeFrame: Baseline to Week 4
measure: Alanine aminotransferase (ALT) levels
timeFrame: Baseline to Week 4
measure: Aspartate aminotransferase (AST) levels
timeFrame: Baseline to Week 4
measure: Creatinine levels
timeFrame: Baseline to Week 4
measure: Uric acid levels
timeFrame: Baseline to Week 4
measure: Waist Circumference
timeFrame: Baseline, week 4
Other outcomes:
Locations:
city: Guadalajara
country: Mexico
facility: Instituto de terapeutica Experimental y Clinica. Centro universitario de Ciencias de la Salud. Universidad de Guadalajara
state: Jalisco
Study officials:
affiliation: University of Guadalajara
name: MANUEL GONZALEZ, PhD
role: PRINCIPAL_INVESTIGATOR
References: