A Research Study of How Semaglutide Works in People With Disease Affecting the Heart and/or Blood Vessels and Type 2 Diabetes

Study Overview
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Brief Summary
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This study looks into how the type 2 diabetes medicine, semaglutide, can prevent risk of heart disease complications and stroke. Participants will either get semaglutide or placebo (dummy medicine) - which treatment is decided by chance. Semaglutide is a new medicine to treat type 2 diabetes and can be prescribed by doctors in some countries. The study medicine will be in a pen, and must be injected with a needle in the stomach, thigh or upper arm once a week. The study will last for 57-63 weeks. Participants will have 10 clinic visits with the study doctor, 5 visits to the specialised clinic for imaging and at least 1 phone contact. Participants' health will be monitored carefully and blood samples will therefore be taken at the clinic visits. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Official Title
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A Trial Investigating the Effect of Semaglutide on Atherosclerosis in Patients With Cardiovascular Disease and Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Semaglutide
* Drug: Placebo (semaglutide)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age above or equal to 50 years at the time of signing informed consent Body mass index equal to or less than 39.9 kg/m^2 Diagnosed with type 2 diabetes 180 daysor more prior to the day of the first screening visit HbA1c 6.0% - 9.0% (42-75 mmol/mol) (both inclusive) Established cardiovascular disease Exclusion Criteria: Hospitalisation for unstable angina pectoris or transient ischaemic attack within 90 days prior to the day of the first screening visit Planned coronary, carotid or peripheral artery revascularisation. Presently classified as being in New York Heart Association (NYHA) equal to or above Class III Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or systemic anti-inflammatory drugs within 90 days prior to the first screening visit. Stable treatment with acetylsalicylic acid for prevention of cardiovascular events and occasional use of propionic acid derivatives drugs (e.g. ibuprofen) is allowed

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide<br>Semaglutide injected once-weekly. Standard dose escalations every 4 weeks will be applied, until the maximum dose of 1.0 mg semaglutide is reached. | Drug: Semaglutide<br>* Subcutaneous (s.c., under the skin) injections for 52 weeks. Participants will remain on their pre-study standard of care treatment (antidiabetic medication and CV medication).<br>|
| Placebo Comparator: Placebo<br>Placebo injected once-weekly. Standard dose escalations every 4 weeks will be applied, until the maximum dose of 1.0 mg placebo is reached. | Drug: Placebo (semaglutide)<br>* Subcutaneous (s.c., under the skin) injections for 52 weeks. Participants will remain on their pre-study standard of care treatment (antidiabetic medication and CV medication).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in maximum target-to-background ratio (TBR) for 18F-fluorodeoxyglucose (FDG) in the carotid arteries | Ratio | From baseline (from 41 days before randomisation) to week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in maximum target-to-background ratio (TBR) for 68Ga-DOTATATE in the carotid arteries | Ratio | From baseline (from 40 days before randomisation) to week 26 | 
| Change in total wall volume of the most diseased carotid artery | mm3 | From baseline (from 41 days before randomisation) to week 52 | 
| Change in lipid rich necrotic core (LRNC) volume of the atherosclerotic plaque in the most diseased carotid artery | mm3 | From baseline (from 41 days before randomisation) to week 52 | 
| Change in average fibrous cap thickness (FCT) of the atherosclerotic plaque in the most diseased carotid artery | mm | From baseline (from 41 days before randomisation) to week 52 |