Novel Therapeutics and Endothelial Dysfunction in T1DM Patients

Study Overview
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Brief Summary
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The aim of study is impact of additional treatment with new antidiabetic drugs (semaglutide or empagliflozine) compared to control group in T1DM patients - impact on endothelial function measured by FMD and FPF, arterial stiffness - measured by PWV, inflammatory biomarkers, markers of oxidative stress and endothelial progenitor cells (CD 34+/VDRL2, CD 133+/VDRL2) and correlation with glucovariability or time in range, measured with CGM system.

Official Title
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Impact of Additional Treatment With Empagliflozin or Semaglutide on Endothelial Function and Other Clinical Parameters and Biomarkers in T1DM Patients

Conditions
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Endothelial Dysfunction, Diabetes Mellitus, Type 1, Biomarkers, Endothelial Progenitor Cells, SGLT 2 Inhibitors, Incretins, Glucose Excursions, FMD, FPF, Arterial Stiffness

Intervention / Treatment
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* Drug: Semaglutide Pen Injector [Ozempic]
* Drug: Empagliflozin 10 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: T1DM HbA1C<=9% prone to CGM system 20 - 70 years Exclusion Criteria: HbA1C >9%, BMI<22, pregnancy or lactation, known hypersensitivity to study drug, malignant disease ( excluded >5 years disease free, bazocellular or planocellular ca of skin), liver cirrhosis child C, eGFR<60 ml/min, chronic inflammatory disease, proliferative diabetic rethinopathy, MEN or medullary thyroid cancer in familly, concomitant drugs with influence on glycemia and antiinflammatory influence (corticosteroids, immunosupresive therapy), Major cardiovascular event last 2 months ( stroke, MI)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 therapeutic arms - adding empagliflozin or semaglutide to basic insulin treatment and control arm in type 1 diabetic patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: GLP 1 agonist<br>semaglutide in titrating doses 0,25 to 1,0 mg - duration of treatment12 weeks adding to insulin sheme (MDI or CII) | Drug: Semaglutide Pen Injector [Ozempic]<br>* GLP 1 agonist<br>|
| Active Comparator: SGLT 2 inhibitor<br>empagliflozin 25 mg - duration of treatment 12 weeks adding to insulin sheme (MDI or CII or hybride system) | Drug: Empagliflozin 10 MG<br>* SGLT 2 inhibitor<br>|
| No Intervention: comparator<br>continuing treatment only with insulin sheme (MDI or CII or hybride system) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluation of endothelial function by flow mediated dilation (FMD) of brachial artery | measurement of dilation of brachial artery (in %) before and after postishemic hyperemia comparing two therapeutic groups and control group before and after intervention | 12 weeks | 
| evaluation of endothelial function by strain gauge plethysmography as change in forearm blood flow | changes in tissue perfusion (ml/100 ml of tissue/min) measured with strange gauge plethysmography as formarm blood flow before and after postishemic reactive hyperemija comparing two therapeutic groups and control group before and after intervention | 12 weeks | 
| evaluation of arterial stiffness with peak wave velocity ( PWV) | measurements of the velocity (m/s) at which arterial blood pressure pulses propagate - comparing two therapeutic groups and control group before and after intervention | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluation of change in inflammatory biomarkers | change of hs CRF, Il6 after treatment comparing two therapeutic groups and control | 12 weeks | 
| evaluation of change in biomarkers of endothelial dysfunction | change in s-VCAM, s-ICAM values before and after intervention - comparing two therapeutic groups and control | 12 weeks | 
| evaluation of endothelial progenitor cells EPC count | change in count of endothelial progenitor cells CD 34*, 133+ as endothelial function markers before and after intervention - comparing two therapeutic groups and control | 12 weeks |