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

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.

• Exenatide LAR (Drug), also known as Bydureon: 2 mg, once weekly subcutaneously before breakfast during 4 weeks.
• Dulaglutide (Drug), also known as Trulicity: .75 mg once weekly subcutaneously before breakfast during 4 weeks.

Primary outcomes

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

Secondary outcomes

• Categories: dipper o non dipper [Baseline to Week 4]: Blood pressure variability will be evaluated with ambulatory blood pressure monitoring (ABPM) for 24 hrs by oscillometric method Microlife WatchBP O3
• Fasting glucose levels [Baseline to Week 4]: 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
• Central and peripheral blood pressure [Baseline to Week 4]: 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.
• Pulse wave velocity [Baseline to Week 4]: 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.
• Cardio-ankle Vascular Index (CAVI) [Baseline to Week 4]: 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.
• Glycosylated hemoglobin [Baseline to Week 4]: 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
• Body Weight [Baseline to Week 4]: 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
• Body Mass Index [Baseline to Week 4]: 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
• Total cholesterol [Baseline to Week 4]: 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
• Triglycerides levels [Baseline to Week 4]: 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
• High density lipoprotein (c-HDL) levels [Baseline to Week 4]: 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
• Alanine aminotransferase (ALT) levels [Baseline to Week 4]: ALT levels will be evaluated at baseline and week 4 with enzymatic/colorimetric techniques
• Aspartate aminotransferase (AST) levels [Baseline to Week 4]: AST levels will be evaluated at baseline and week 4 with enzymatic/colorimetric techniques \[Time Frame: Baseline to Week 4
• Creatinine levels [Baseline to Week 4]: Creatinine levels will be evaluated at baseline and week 4 with enzymatic/colorimetric techniques
• Uric acid levels [Baseline to Week 4]: Uric acid levels will be evaluated at baseline and week 4 with enzymatic/colorimetric techniques
• Waist Circumference [Baseline, week 4]: Waist circumference will be evaluated at baseline and at week 4 with a flexible tape

Sex: All, ages: 31 Years to 60 Years

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

• MANUEL GONZALEZ, PhD, Principal investigator, University of Guadalajara