Diabetes Mellitus, Type 2Phase 1NCT04032197
A Research Study of How Semaglutide Works in People With Disease Affecting the Heart and/or Blood Vessels and Type 2 Diabetes
A Phase 1 study testing Semaglutide in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 4 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Semaglutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 101 participants
- Where
- 4 sitesin 3 countries
- Study dates
- 12 Aug 2019to 6 Jun 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 3 countries.
4 sites in 3 countries
Sweden2 sites
Karolinska Universitetssjukhuset Solna,FOU Tema Hjärta Kärl
Stockholm, 171 64
CTC Clinical Trial Consultants AB, Uppsala
Uppsala, 75237
About this study
Official title: 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.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Semaglutide, Placebo (semaglutide)
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SemaglutideDrug
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 (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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo (semaglutide) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in maximum target-to-background ratio (TBR) for 18F-fluorodeoxyglucose (FDG) in the carotid arteries
Ratio
Measured: 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
Ratio
Measured: From baseline (from 40 days before randomisation) to week 26
Change in total wall volume of the most diseased carotid artery
mm3
Measured: 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
Measured: 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
Measured: From baseline (from 41 days before randomisation) to week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2019
- Study start12 Aug 2019
- Primary completion16 Dec 2022
- Study completion6 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Reporting Anchor and Disclosure (1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04032197
- Sponsor's protocol ID
- NN9535-4430
- Other IDs
- U1111-1215-4058, 2018-002289-38, 2018
- Status last verified
- Apr 2025
- First submitted
- 22 Jul 2019
- Last updated
- 29 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Publications
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.
PubMed 40345413
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Trial Investigating the Effect of Semaglutide on Atherosclerosis in Patients With Cardiovascular Disease and Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT04032197
- Acronym / sponsor ID
- NN9535-4430
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 12 Aug 2019 (actual)
- Primary completion
- 16 Dec 2022 (actual)
- Study completion
- 6 Jun 2023 (actual)
- First posted
- 25 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Semaglutide | Experimental | Drug: SemaglutideSemaglutide injected once-weekly. Standard dose escalations every 4 weeks will be applied, until the maximum dose of 1.0 mg semaglutide is reached. |
| Placebo | Placebo comparator | Drug: Placebo (semaglutide)Placebo injected once-weekly. Standard dose escalations every 4 weeks will be applied, until the maximum dose of 1.0 mg placebo is reached. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SemaglutideSubcutaneous (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). | Drug | Semaglutide |
| 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). | Drug | Placebo |
Primary outcome
Change in maximum target-to-background ratio (TBR) for 18F-fluorodeoxyglucose (FDG) in the carotid arteries
Time frame: From baseline (from 41 days before randomisation) to week 26
Ratio
4 secondary outcomes
Change in maximum target-to-background ratio (TBR) for 68Ga-DOTATATE in the carotid arteries
Time frame: From baseline (from 40 days before randomisation) to week 26
Change in total wall volume of the most diseased carotid artery
Time frame: 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
Time frame: 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
Time frame: From baseline (from 41 days before randomisation) to week 52
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2025.
- Derived from this study: PubMed 40345413James 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.
- Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Reporting Anchor and Disclosure (1452) study director
Novo Nordisk A/S
4 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Semaglutide in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 4 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Sweden, Austria, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in maximum target-to-background ratio (TBR) for 18F-fluorodeoxyglucose (FDG) in the carotid arteries (time frame: From baseline (from 41 days before randomisation) to week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04032197, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2025.