The Effect of Semaglutide on Cardiovascular Markers and Liver Function

NCT06301191 | Recruiting

• 1 other identifier: 133/21-02-2022
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Fifty patients with diabetes mellitus type 2 and non-alcoholic fatty liver disease (NAFLD) will be enrolled in the study. 25 patients will treated with semaglutide and 25 patients with dipeptidyl peptidase 4 (D-PP4) inhibitors. At baseline, at four and at 12 months will evaluate the endothelial, cardiovascular and liver function.

Conditions

Diabetes Type 2

Outcome Measures

Primary Outcomes (3)

• Comparison of arterial stiffness markers difference among treatment groups

  Comparison of pulse wave velocity difference among treatment groups. Two non-invasive pressure sensors will be used to record the carotid and femoral waveforms and the distance between the two arterial sites will be measured with a tape measure. Pulse wave velocity is calculated as the distance divided by transit time between waves (m/s).

  12 months

• Comparison of endothelial glycocalyx thickness difference among treatment groups

  The investigators will measure the perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5 to 25 μm) using Sidestream Darkfield imaging that provides a direct, noninvasive, and fast method for the assessment of the endothelial glycocalyx. The PBR is the cell-poor layer which results from the phase separation between the flowing red blood cells (RBC) and plasma on the surface of the microvessel lumen. The PBR includes the most luminal part of glycocalyx that does allow cell penetration. Thus, an increased perfused boundary region is consistent with deeper penetration of erythrocytes into glycocalyx, indicating a loss of glycocalyx barrier properties and is a marker of reduced glycocalyx thickness.

  12 months

• Comparison of liver stiffness difference among treatment groups

  CAP score will be used as an index of liver fat content, with normal values being \< 238 dB/m. \<237 dB/m (S0, no steatosis), 237 -259 dB/m (S1, mild steatosis), 259 -291 dB/m (S2, moderate steatosis), and 291 -400 dB/m (S3,severe steatosis). E score will be used as an index of liver fibrosis. The cut-off values for fibrosis (F) were as follows:(1) \<5.5 kPa (F0, no fibrosis), (2) 5.5-8.0 kPa (F1, mild fibrosis), (3) 8.0-10.0 kPa (F2, moderate fibrosis),(4) 11.0-16.0 kPa (F3, severe fibrosis), and (5) \>16.0 kPa (F4, cirrhosis).

  12 months

Study Arms (2)

Semaglutide group

25 patients treated with semaglutide. Pulse wave velocity, aumentation index, SBPao and PPao with Arteriograph, Mobilograph and Complior, and perfused boundary region (PBR) of sublingual vessels using a high-resolution camera with Sideview Darkfield Imaging technique (Microscan, Glucockeck) will be evaluated. PBR consists the cell-free space which is formed from the separation of red blood cells from plasma at the surface of the endothelial glycocalyx.Liver steatosis and stiffness will be measured using Fibroscan® Mini+ 430 (Echosens, Paris, Île-de-France). CAP score will be used as an index of liver fat content, with normal values being \< 238 dB/m. E score will be used as an index of liver fibrosis, with normal values being 2- 6 kPa. Blood glucose, glycosylated hemoglobin (HbA1c) and a full lipidemic profile will be measured before and at 4 and 12 months of treatment.

Drug: Semaglutide, 1.0 mg/mL

D-PP4 group

25 patients treated with D-PP4 inhibitors. Pulse wave velocity, augmentation index, SBPao and PPao with Arteriograph, Mobilograph and Complior, and perfused boundary region (PBR) of sublingual vessels using a high-resolution camera with Sideview Darkfield Imaging technique (Microscan, Glucockeck) will be evaluated. PBR consists the cell-free space which is formed from the separation of red blood cells from plasma at the surface of the endothelial glycocalyx.Liver steatosis and stiffness will be measured using Fibroscan® Mini+ 430 (Echosens, Paris, Île-de-France). CAP score will be used as an index of liver fat content, with normal values being \< 238 dB/m. E score will be used as an index of liver fibrosis, with normal values being 2- 6 kPa. Blood glucose, glycosylated hemoglobin (HbA1c) and a full lipidemic profile will be measured before and at 4 and 12 months of treatment

Drug: Dipeptidyl Peptidase 4 inhibitor

Interventions

Semaglutide, 1.0 mg/mL DRUG

Semaglutide, 1.0 mg/mL

Semaglutide group

Dipeptidyl Peptidase 4 inhibitor DRUG

Dipeptidyl Peptidase 4 inhibitor

D-PP4 group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

50 subjects with T2DM and NAFLD, who attended the Diabetes Outpatients Clinic were enrolled in the study. 25 patients will reciece semaglutide 1 mg (treatment group) and 25 patients will receive DPP-4 inhibitors (either linagliptin or alogliptin or vildagliptin or sitagliptin - control group). Exclusion criteria were malignancies, chronic inflammatory disease, chronic kidney disease (estimated glomerular filtration rate \<60 ml/min/m2 for a period of at least 90 days) peripheral vascular disease, retinopathy, and previous therapy with a Glucagon-like peptide-1 agonist. None of the female patients was on hormone replacement treatment.

You may qualify if:

• Diabetes Mellitus type 2
• NAFLD

You may not qualify if:

• malignancies
• chronic inflammatory disease
• chronic kidney disease (estimated glomerular filtration rate \<60 ml/min/m2 for a period of at least 90 days)
• peripheral vascular disease
• retinopathy
• previous therapy with a Glucagon-like peptide-1 agonist.
• None of the female patients was on hormone replacement treatment.

Sponsors & Collaborators

• Attikon Hospital: lead

Study Sites (1)

Attikon University General Hospital

Athens, 12462, Greece

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood sample obtained from the subjects for oxidative stress markers (malondialdehyde and protein carbonyls), nitrites and nitrates, N-terminal pro B-type natriuretic peptide (NT-proBNP) measuring.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

semaglutide; Dipeptidyl-Peptidase IV Inhibitors

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Central Study Contacts

VAIA LAMBADIARI, Professor

CONTACT

2105831148; vlambad@otenet.gr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Internal Medicine-Endocrinology

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: March 8, 2024
• Study Start: March 1, 2022
• Primary Completion: March 1, 2023
• Study Completion: May 1, 2024
• Last Updated: March 8, 2024

Record last verified: 2024-03

Locations

GR (1)