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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo (semaglutide)

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Clinical Trials Unit / Center for Medical Research
• Denmark
  • Herlev, Denmark, 2730
    • Steno Diabetes Center Copenhagen
• Sweden
  • Stockholm, Sweden, 171 64
    • Karolinska Universitetssjukhuset Solna,FOU Tema Hjärta Kärl
  • Uppsala, Sweden, 75237
    • CTC Clinical Trial Consultants AB, Uppsala

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide; 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; 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).
Placebo Comparator: Placebo; 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); 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).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2019
• Primary Completion (Actual): December 16, 2022
• Study Completion (Actual): June 6, 2023

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 25, 2019

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 27, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: NN9535-4430; U1111-1215-4058 (Other Identifier: World Health Organization (WHO)); 2018-002289-38 (Registry Identifier: European Medicines Agency (EudraCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No