Semaglutide Anti-Atherosclerotic Mechanisms of Action Study in Type 2 Diabetes Patients

Study Overview
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Brief Summary
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Diabetes is a chronic disease characterized by chronic hyperglycaemia, causing microvascular and macrovascular complications. The latter lead to various disabilities: blindness, end-stage renal failure, nerve damage, formation of leg ulcers, and atherosclerosis. In people with type 2 diabetes, the probability of these atherosclerosis associated complications is twice as high as in people without diabetes. Cardiovascular diseases are also the main cause of mortality in people with diabetes. Preventive measures are therefore crucial. In people with type 2 diabetes, in addition to good glycaemic control, the choice of antidiabetic drugs is also important. Large-scale research has shown that certain glucagon-like peptide (GLP-1) receptor agonists, in addition to improving the regulation of diabetes, also have a significant effect on reducing the macrovascular complications. It is now possible to use semaglutide, a GLP-1 receptor agonist, in the tablet form. Semaglutide lowers blood sugar only when the blood sugar value rises, due to food in the digestive tract, Thus, not increasing the risk of hypoglycaemia. In addition, semaglutide has a significant effect on weight loss and very beneficial, protective effects on the cardiovascular system. Large studies have shown that in its injectable form, it significantly reduces the incidence of cardiovascular death in patients with type 2 diabetes. Therefore, the aim of the present study is to examine how semaglutide provides protective effects on the cardiovascular system and reduces the risk of diabetes type 2 associated complications. The present study will include 100 people with type 2 diabetes and last for 12 months. The subjects will receive a semaglutide oral tablet daily in addition to their current treatment (combination of metformin and a sulphonyl urea). At the beginning of the study, after 6 months and at the end of the study (after 12 months of treatment), a detailed clinical examination will be performed and blood will be taken for laboratory parameters. In addition to basic blood tests, inflammatory and oxidative stress parameters, as well as lipid fractions parameters will also be assessed. Ultrasound examination of the changes in the carotid arteries and measures of additional properties of the arteries will also be performed. The confidentiality of the data of the participants in the research will be ensured, as the data obtained during the investigation will be encrypted before processing.

Official Title
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Semaglutide Anti-Atherosclerotic Mechanisms of Action Study in Type 2 Diabetes Patients

Conditions
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Diabetes Mellitus, Type 2, Atherosclerosis

Intervention / Treatment
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* Drug: Semaglutide Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type 2 diabetes therapy including at least metformin 1000 mg and sulphonyl urea at least half of the maximal dose BMI > or = 30 kg/m2 HbA1c < or = 8,5% associated risk factors including smoking, dyslipidaemia, arterial hypertension, chronic kidney disease stage 1 to 3. Exclusion Criteria: therapy with injectable GLP-1 receptor agonist ongoing or was taking place in the last year manifested cardiovascular disease heart failure chronic kidney disease stages 4 and 5 advanced liver disease proliferative retinopathy or maculopathy

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 60 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Interventional Arm<br>Beside metformin and sulphonyl urea treatment, the active, interventional arm, will be receiving Semaglutide Oral Tablets as per protocol, 3 mg for the first month, 7 mg in the second month and 14 mg form the third month onwards. | Drug: Semaglutide Oral Tablet<br>* Semaglutide Oral Tablets will be introduced to the active arm as per protocol for regular therapy introduction.<br>* Other names: Rybelsus;|
| No Intervention: Comparative Arm<br>This group will not be receiving the additional therapy besides metformin and sulphonyl urea treatment. After 6 months a revaluation of glycemic control will be performed, if needed, rescue therapy with basal insulin will be implemented. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in morphological arterial wall characteristics | Ultrasonographic assessment of cIMT (in millimetres) | 1 year | 
| Change in functional arterial wall characteristics | Endothelial function assessment by EndoPAT | 1 year | 
| Change in structural arterial wall characteristics | Arterial stiffness assessment by Sphygmocor device (in meters per second) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in atherogenic small dense low-density lipoproteins (sdLDL) | Assessment by gel electrophoresis | 1 year | 
| Change in glycated haemoglobin (HbA1c) | Assessment by biochemical methods | 1 year | 
| Change in high sensitivity C-reactive protein (hsCRP) | Assessment by biochemical methods | 1 year | 
| Correlations between changes in rate of cIMT reduction, % of endothelial function improvement and rate of arterial stiffness reduction on one hand and changes in concentration of sdLDL, % of HbA1c and concentration of hsCRP on the other | Statistical methods | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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semaglutide, atherosclerosis, diabetes mellitus type 2