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

NCT04032197 | Completed Phase 1 FDA Drug

• 3 other identifiers: NN9535-4430U1111-1215-40582018-002289-38
• Study Type: interventional
• Target: 101
• Locations: 3 countries
• Sites: 4

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Change in maximum target-to-background ratio (TBR) for 68Ga-DOTATATE in the carotid arteries

  From baseline (from 40 days before randomisation) to week 26

• Change in total wall volume of the most diseased carotid artery

  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

  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

  From baseline (from 41 days before randomisation) to week 52

Study Arms (2)

Semaglutide

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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)

Interventions

Semaglutide DRUG

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).

Semaglutide

Placebo (semaglutide) DRUG

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

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (4)

Clinical Trials Unit / Center for Medical Research

Graz, 8010, Austria

Location

Steno Diabetes Center Copenhagen

Herlev, 2730, Denmark

Location

Karolinska Universitetssjukhuset Solna,FOU Tema Hjärta Kärl

Stockholm, 171 64, Sweden

Location

CTC Clinical Trial Consultants AB, Uppsala

Uppsala, 75237, Sweden

Location

Related Publications (1)

• James S, Christoffersen AD, David JP, Hacker M, Jensen MDRJ, Mellbin L, Pieber TR, Ripa RS, Rossing P, Svehlikova E, Kjaer A. Effect of once-weekly subcutaneous semaglutide on arterial inflammation in people with type 2 diabetes and cardiovascular disease using PET-MRI: Primary results of a randomized, double-blind, placebo-controlled trial. Am Heart J. 2025 Nov;289:17-27. doi: 10.1016/j.ahj.2025.05.001. Epub 2025 May 7.

  PMID: 40345413 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Clinical Reporting Anchor and Disclosure (1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sponsor staff involved in the clinical trial is masked according to company standard procedures
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2019
• First Posted: July 25, 2019
• Study Start: August 12, 2019
• Primary Completion: December 16, 2022
• Study Completion: June 6, 2023
• Last Updated: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share

Locations

AU (1); DK (1); SE (2)