Assessing Incretin Therapy for Cardiovascular Risk Reduction and Diabetes Remission( ITCRDR Study)

Phase 4

• Conditions: Diabetes Mellitus; Cardiovascular Diseases; Cerebrovascular Disease
• Interventions: Drug: Metformin; Drug: semaglutide

• Registration Number: NCT06959784
• Lead Sponsor: China-Japan Friendship Hospital

Brief Summary

This study used the diabetes prevention and follow-up research queue in Daqing and the public database of UKbiobank to evaluate the risk factors of cardiovascular and cerebrovascular events in diabetes patients, and built the first risk prediction model of cardiovascular and cerebrovascular events in diabetes patients based on the Chinese population follow-up queue and externally verified, so as to identify high-risk groups and guide the early prevention of cardiovascular and cerebrovascular diseases in diabetes patients. To evaluate the effect of incretin drugs on reducing the risk of cardiovascular and cerebrovascular events, and the impact on the remission rate of diabetes in people with initial diabetes, a randomized, multicenter, controlled clinical study was conducted. The long-term follow-up of 2 years was conducted to evaluate whether the cardiovascular and cerebrovascular risks of those who stopped drug treatment after remission of diabetes compared with those who continued drug treatment were reduced, as well as the long-term impact of incretin on cardiovascular and cerebrovascular risks and the role of long-term mitigation of diabetes.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-01-01
• Status Verified: 2025-04
• Study First Submitted: 2025-04-16
• Study First Submitted QC: 2025-05-05
• Last Update Submitted: 2025-05-05
• Study First Posted: 2025-05-07
• Last Update Posted: 2025-05-07
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 142

Inclusion Criteria

• Newly diagnosed diabetes, with no previous use of hypoglycemic medications or having discontinued such medications for more than 3 months.
• Blood glucose elevation detected within one year (fasting blood glucose exceeding 7 mmol/L, postprandial blood glucose or random blood glucose exceeding 11.1 mmol/L).
• Age between 30 and 70 years (inclusive of boundary values).
• Hemoglobin A1c between 7% and 10% (inclusive of boundary values).
• BMI between 24 and 32.5 kg/m² (inclusive of boundary values).

Exclusion Criteria

• History of coronary heart disease or cerebral infarction.
• Severe liver or kidney disease: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN); glomerular filtration rate less than 30 ml/min/1.73 m².
• History of malignant tumors.
• Use of systemic glucocorticoids (excluding local applications or inhalants) for one week or more within the three months prior to screening.
• Positive urine pregnancy test in women of childbearing age.
• History of pancreatitis, or amylase and/or lipase > 3 times the ULN.
• Personal history or family history of medullary thyroid carcinoma (MTC) in first-degree relatives, or genetic predisposition to MTC (such as multiple endocrine neoplasia syndrome).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin control group	Metformin	The metformin control group received metformin (gradually increased to 1 g bid) for 24 weeks (6 months)
semaglutide group	semaglutide	The Semaglutide intervention group received semaglutide (starting at 0.25mg qw and increasing to 0.5mg qw after four weeks) for 24 weeks (6 months).

Primary Outcome Measures

Name	Time	Method
Cardiovascular and cerebrovascular event risk score	One-year follow-up	The cardiovascular and cerebrovascular event score (0-100%)is based on the cardiovascular and cerebrovascular event risk prediction model for diabetic patients established in Objective 1. In this prediction model, age, gender, smoking status, body mass index, waist circumference, glycated hemoglobin, blood sugar, blood pressure, and blood lipids correspond to certain scores. Higher scores indicate a higher risk of cardiovascular and cerebrovascular events and a worse outcome.
Major Adverse Cardiovascular Events	Baseline and every 12 weeks until 96 weeks	The Mace event includes cardiovascular death, non-fatal myocardial infarction and non-fatal stroke.
Cerebrovascular disease events	Baseline and every 12 weeks until 96 weeks	Cerebrovascular diseases include ischemic stroke, hemorrhagic stroke, transient ischemic attack, cerebral vascular malformation, etc.

Secondary Outcome Measures

Name	Time	Method
The remission rate of diabetes	at 9 months, 1 year and 2 years of follow-up
Glycated hemoglobin	Baseline and every 12 weeks until 96 weeks	Reduced levels of glycated hemoglobin
Fasting and postprandial blood glucose levels	at 2 year and 8 year of follow-up
pancreatic islet function	Baseline, 48 weeks and 96 weeks	The study evaluated pancreatic islet cell function by testing fasting insulin, insulin one hour after a steamed bread meal, and insulin two hours after a steamed bread meal.
Routine urine examination	Baseline, 48 weeks and 96 weeks	Evaluate the levels of red blood cells, white blood cells, urine glucose, urine ketones, and urine protein in urine through urine routine testing.
Urine microalbumin	Baseline, 48 weeks and 96 weeks	Urine microalbuminuria for early assessment of renal damage.
Heart rhythm	Baseline, 48 weeks and 96 weeks	The heart rhythm of the subjects were measured by electrocardiogram when they were at rest.
Carotid artery peak diastolic velocity	Baseline, 48 weeks and 96 weeks	Evaluate the diastolic peak blood flow velocity through carotid artery ultrasound.
Carotid resistance index	Baseline, 48 weeks and 96 weeks	Evaluate resistance index through carotid artery ultrasound. Carotid resistance index = (peak systolic velocity - end diastolic velocity) / peak systolic velocity
common carotid artery diameter	Baseline, 48 weeks and 96 weeks	Evaluate the common carotid artery diameter through carotid artery ultrasound.
Carotid artery wall thickness	Baseline, 48 weeks and 96 weeks	Evaluate the wall thickness through carotid artery ultrasound.
Carotid Intima-media Thickness	Baseline, 48 weeks and 96 weeks	Evaluate the intimal thickness through carotid artery ultrasound.
Heart rate	Baseline, 48 weeks and 96 weeks	The heart rate of the subjects were measured by electrocardiogram when they were at rest.
Carotid artery peak systolic velocity	Baseline, 48 weeks and 96 weeks	Evaluate the systolic peak blood flow velocity through carotid artery ultrasound.

Trial Locations

Locations (1)

China-Japan Friendship hospital; 🇨🇳 Beijing, China