Clinical trial NCT05147896: Semaglutide Anti-Atherosclerotic Mechanisms of Action Study in Type 2 Diabetes Patients
Official title: Semaglutide Anti-Atherosclerotic Mechanisms of Action Study in Type 2 Diabetes Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Atherosclerosis
Keywords: semaglutide
atherosclerosis
diabetes mellitus type 2
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
Collaborators: name: University of Palermo
First posted: 2021-12-07
Enrollment: 100
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in morphological arterial wall characteristics
timeFrame: 1 year
measure: Change in functional arterial wall characteristics
timeFrame: 1 year
measure: Change in structural arterial wall characteristics
timeFrame: 1 year
Secondary outcomes:
measure: Change in atherogenic small dense low-density lipoproteins (sdLDL)
timeFrame: 1 year
measure: Change in glycated haemoglobin (HbA1c)
timeFrame: 1 year
measure: Change in high sensitivity C-reactive protein (hsCRP)
timeFrame: 1 year
measure: 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
timeFrame: 1 year
Other outcomes:
Locations:
city: Ljubljana
country: Slovenia
facility: UMC Ljubljana, Diabetes Outpatient Clinic
Study officials:
affiliation: University Medical Centre Ljubljana
name: Andrej Janež, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Janic M, Rizzo M, Cosentino F, Pantea Stoian A, Lunder M, Sabovic M, Janez A. Effect of Oral Semaglutide on Cardiovascular Parameters and Their Mechanisms in Patients with Type 2 Diabetes: Rationale and Design of the Semaglutide Anti-Atherosclerotic Mechanisms of Action Study (SAMAS). Diabetes Ther. 2022 Apr;13(4):795-810. doi: 10.1007/s13300-022-01226-y. Epub 2022 Mar 8.