Effect of Exenatide LAR or Dulaglutide on the Variability of 24-hour Heart Rate and Blood Pressure in Type 2 Diabetes

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.

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.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Exenatide LAR; Drug: Dulaglutide

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: MANUEL GONZALEZ, PhD; Phone Number: 34212 +523310585200; Email: uiec@prodigy.net.mx
• Study Contact Backup: Name: KARINA PEREZ, PhD; Phone Number: 34212 +523310585200; Email: karina2410@hotmail.com

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Recruiting
      • Instituto de Terapeútica Experimental y Clínica. Centro Universitario de Ciencias de la Salud. Universidad de Guadalajara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Drug: Exenatide LAR; Exenatide LAR 2 mg, once weekly subcutaneously before breakfast during 4 weeks.	Drug: Exenatide LAR; 2 mg, once weekly subcutaneously before breakfast during 4 weeks.; Other Names: Bydureon
Active Comparator: Drug: Dulaglutide; Dulaglutide .75 mg, once weekly subcutaneously Before breakfast during 4 weeks.	Drug: Dulaglutide; .75 mg once weekly subcutaneously before breakfast during 4 weeks.; Other Names: Trulicity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart rate: nighttime, daytime and 24-h	heart rate variability will be evaluated with ambulatory blood pressure monitoring (ABPM) for 24 h by oscillometric method Microlife WatchBP O3	Baseline to Week 4
Systolic blood pressure, daytime, night and 24 h	Blood pressure variability will be evaluated with ambulatory blood pressure monitoring (ABPM) for 24 h by oscillometric method Microlife WatchBP O33.	Baseline to Week 4
Diastolic blood pressure, daytime, night and 24 h	Blood pressure variability will be evaluated with ambulatory blood pressure monitoring (ABPM) for 24 h by oscillometric method Microlife WatchBP O3	Baseline to Week 4
Blood pressure	Blood pressure will be measured at baseline and week 4 with a digital sphygmomanometer and the entered values reflect the blood pressure.	Baseline to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Categories: dipper o non dipper	Blood pressure variability will be evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hrs by oscillometric method Microlife WatchBP O3	Baseline to Week 4
Fasting glucose levels	The fasting glucose levels will be evaluated at baseline and week 4 with enzymatic/colorimetric techniques and the entered values reflect the fasting glucose level at week 4	Baseline to Week 4
Central and peripheral blood pressure	To determine and compare the effect of administration of Exenatide LAR or Dulaglutide on Central and peripheral blood pressure through HEM will be evaluated at baseline and week 4.	Baseline to Week 4
Pulse wave velocity	To determine and compare the effect of administration of Exenatide LAR or Dulaglutide on pulse wave velocity through VP1000-plus with Ankle-Brachial Index will be evaluated at baseline and week 4.	Baseline to Week 4
Cardio-ankle Vascular Index (CAVI)	To determine and compare the effect of administration of Exenatide LAR or Dulaglutide on arterial stiffness through Cardio-ankle Vascular Index (CAVI) will be evaluated at baseline and week 4.	Baseline to Week 4
Glycosylated hemoglobin	Glycosylated hemoglobin will be evaluated at baseline and week 4 by high pressure liquid chromatography (HPLC) and the entered values reflect the glycosylated hemoglobin at week 4	Baseline to Week 4
Body Weight	The body weight will be measured at baseline and week 4 with a bioimpedance balance and the entered values reflect the body weight at week 4	Baseline to Week 4
Body Mass Index	Body Mass Index will be calculated at baseline and week 4 with the Quetelet index formula and the entered values reflect the body mass index at week 4	Baseline to Week 4
Total cholesterol	Total cholesterol levels will be evaluated at baseline and week 4 by enzymatic/colorimetric techniques and the entered values reflect the total cholesterol level at week 4	Baseline to Week 4
Triglycerides levels	Triglycerides levels will be evaluated at baseline and week 4 with enzymatic/colorimetric techniques and the entered values reflect the triglycerides level at week 4	Baseline to Week 4
High density lipoprotein (c-HDL) levels	c-HDL levels will be evaluated at baseline and week 4 with enzymatic/colorimetric techniques and the entered values reflect the c-HDL level at week 4	Baseline to Week 4
Alanine aminotransferase (ALT) levels	ALT levels will be evaluated at baseline and week 4 with enzymatic/colorimetric techniques	Baseline to Week 4
Aspartate aminotransferase (AST) levels	AST levels will be evaluated at baseline and week 4 with enzymatic/colorimetric techniques [Time Frame: Baseline to Week 4	Baseline to Week 4
Creatinine levels	Creatinine levels will be evaluated at baseline and week 4 with enzymatic/colorimetric techniques	Baseline to Week 4
Uric acid levels	Uric acid levels will be evaluated at baseline and week 4 with enzymatic/colorimetric techniques	Baseline to Week 4
Waist Circumference	Waist circumference will be evaluated at baseline and at week 4 with a flexible tape	Baseline, week 4

Collaborators and Investigators

• Sponsor: University of Guadalajara
• Investigators: Principal Investigator: MANUEL GONZALEZ, PhD, University of Guadalajara

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2017
• Primary Completion (Anticipated): November 30, 2021
• Study Completion (Anticipated): November 30, 2021

Study Registration Dates

• First Submitted: February 13, 2018
• First Submitted That Met QC Criteria: February 21, 2018
• First Posted (Actual): February 23, 2018

Study Record Updates

• Last Update Posted (Actual): March 26, 2020
• Last Update Submitted That Met QC Criteria: March 24, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Diabetes; Variability of blood pressure; ABPM; Hyperglycemia; Exenatide LAR or Dulaglutide 0.75mg; Glucagon-like peptide analogues type 1 (GLP1).
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Dulaglutide; Exenatide
• Other Study ID Numbers: Exenatida LAR Dulaglutida-with

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No