Type 1 Diabetes Impacts of Semaglutide on Cardiovascular Outcomes

Study Overview
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Brief Summary
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This trial plans to learn more about the effects of a medication, semaglutide, on cardiovascular function, kidney function, and insulin sensitivity in adults with type 1 diabetes. This medication has been effective in reducing cardiovascular disease and diabetic kidney disease and improving glucose control and BMI in adults with type 2 diabetes. This study aims to look at how well the medication works in people with type 1 diabetes. Semaglutide is not approved by the FDA to be used in this way. These procedures are considered to be experimental.

Official Title
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Type 1 Diabetes Impacts of Semaglutide on Cardiovascular Outcomes

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Semaglutide Pen Injector
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-49 years Antibody + Type 1 Diabetes (T1D) <30 years Insulin pump or automated insulin delivery systems Estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2 Stable doses of drugs altering cardiovascular and renal function (e.g., Angiotensin-Converting Enzyme Inhibitor (ACEi), Angiotensin Receptor Blocker (ARB), statins, diuretics) BMI 20-35 kg/m2 Adequate contraceptive method for females Exclusion Criteria: HbA1c >9%, recent diabetic ketoacidosis (DKA) or hospitalization Congenital heart disease, anemia, diabetic retinopathy History/family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2 (MEN2), pancreatitis Current/planned pregnancy or nursing Uncontrolled thyroid disease or hypertension (HTN) (≥ 160/100 mm Hg despite optimal therapy) Use of other non-insulin diabetes medications, insulin sensitizing medications, or systemic steroids in past 3 months Use of atypical antipsychotics Significant systemic illness such as cancer Shellfish/iodine allergy (only exclusionary to iohexol clearance procedure) MRI or PAH contraindications (only exclusionary to MRI and PAH procedures), GLP-1RA allergy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Experimental: Semaglutide<br>Participants will receive 0.25 mg once weekly semaglutide injection for 4 weeks. Participants will receive 0.50 mg once weekly semaglutide injection for 4 weeks. Participants will receive 1.0 mg once weekly semaglutide injection for 6 months. | Drug: Semaglutide Pen Injector<br>* Semaglutide injection<br>* Other names: Ozempic;|
| Placebo Comparator: Placebo<br>Participants will receive 0.25 mg once weekly placebo injection for 4 weeks. Participants will receive 0.50 mg once weekly placebo injection for 4 weeks. Participants will receive 1.0 mg once weekly placebo injection for 6 months. | Drug: Placebo<br>* Semaglutide placebo injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Ascending Aortic Pulse Wave Velocity (AA PWV) | AA PWV is a measure of central arterial stiffness. A lower value indicates a better outcome. | Baseline, month 8 | 
| Change in Carotid and Femoral Artery Pulse Wave Velocity (CF-PWV) | CF-PWV is a measure of peripheral arterial stiffness. A lower value indicates a better outcome. | Baseline, month 8 | 
| Change in Carotid and Radial Artery Pulse Wave Velocity (CR-PWV) | CR-PWV is a measure of peripheral arterial stiffness. A lower value indicates a better outcome. | Baseline, month 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Insulin Sensitivity | Insulin Sensitivity is a measure of how well the body responds insulin. A higher value indicates a better outcome; a lower value indicates a worse outcome. | Baseline, month 8 | 
| Change in Renal Vascular Resistance (RVR) | RVR is a measure of mean arterial pressure to renal blood flow. A higher value indicates a worse outcome. | Baseline, month 8 |