The Influence of Oral Semaglutide for Vascular Inflammation in Japanese Patients with Type 2 Diabetes

JRCT ID: jRCTs071220027

Registered date:25/07/2022

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Patients with type 2 diabetes and a glycated hemoglobin level of 7% or more
• Date of first enrollment: 25/07/2022
• Target sample size: 60
• Study type: Interventional

Intervention(s)

Eligible patients were randomly assigned in a 1:1 ratio to receive once-daily oral semaglutide or oral hypoglycemic agents other than semaglutide.

The patients in the semaglutide group were initially treated with 3 mg/day of semaglutide orally for the first 4 weeks. Then the dose was increased to 7 mg/day for the next 4 weeks, and maximally maintained at 14 mg/day thereafter, if needed.

Outcome(s)

• Primary Outcome: Changes from baseline after 6 months of treatment in vascular inflammation measured by blood-normalized standardized uptake value, known as a target-to-background ratio by FDG-PET/CT

Secondary Outcome

1. Changes from baseline in FDG activity witin the myocardium, liver, spleen, brain, and fat as measured by FDG-PET/CT
2. Changes from baseline in subcutaneous and visceral fat volume as measured by CT
3. Changes from baseline in daily energy intake and the intake of different nutritional components
4. Changes from baseline in weight, waist circumference, resting blood pressure, and resting heart rate
5. Changes from baseline in serum and urinary diabetic markers including fasting blood glucose, fasting insulin, glycated hemoglobin, urinary glucose excretion, urinary protein excretion, and urinary L-FABP
6. Changes from baseline in lipid profiles (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides)
7. Changes from baseline in serum biomarkers of inflammation and atherosclerosis (high-sensitivity C-reactive protein, asymmetric dimethylarginine, adiponectin, advanced glycation end-products, receptor for advanced glycation end-products, pigment epithelium-derived factor, leptin, ghrelin)
8. Changes from baseline in cardio-ankle vascular index and brachial artery flow-mediated dilation
9. Changes from baseline in accumulated advanced glycation end-products in skin collagen measured with skin autofluorescence by AGE READER

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 90age old
• Gender: Both

Include criteria

1) Patients with type 2 diabetes and a glycated hemoglobin level of 7% or more
2) Age of 18 to 90 years at screening and written informed consent to participate in this study
3) Age of less than 60 years with established cardiovascular disease, or age of 60 years or more with at least one cardiovascular risk factor
4) Oral hypoglycemic agents, lipid lowering agents, antihypertensive agents, and antiplatelet agents and doses of them unchanged within 90 days prior to screening
5) No treatment with any incretin-based antidiabetic agents (DPP-4 inhibitors or GLP-1 receptor agonists) within 90 days prior to screening

Exclude criteria

1. Patients with diabetic ketoacidosis or hyperglycemic hyperosmolar state
2. Patients with severe infection or surgical emergency
3. Patients with a history of hypersensitivity to study drugs
4. Pregnant patients
5. Patients with significant hepatic disorders or liver cirrhosis
6. Patients with a history of stomach resection
7. Patients with a fasting plasma glucose level of 200 mg/dL or more
8. Patients treated with insulin therapy
9. Patients with malignant neoplasms
10. Patients with active inflammatory diseases
11. Patients judged to be inappropriate to participate in this study by investigators
12. Patients treated with a DPP-4 inhibitor or a GLP-1 receptor agonist within 90 days before screening

Related Information

• Primary Sponsor: Tahara Nobuhiro