Diabetes Mellitus, Type 2Phase 4ASCEND PLUSNCT05441267
A Study of Cardiovascular Events iN Diabetes Plus
A Phase 4 study testing Semaglutide Oral Tablet in people with Diabetes Mellitus, Type 2, run by University of Oxford at 1 site in United Kingdom.
Trial summary
ASCEND PLUS is testing whether, for people with type 2 diabetes who have not previously had a heart attack or stroke, regularly taking a tablet called semaglutide can safely help to reduce heart attacks, strokes, mini-strokes, the need for any procedures to unblock or bypass an artery to their heart, and the chance of… Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Semaglutide Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21,296 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 13 Mar 2023to 17 Aug 2048
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged at least 55 years at the time of the Screening assessment
- Type 2 Diabetes Mellitus (based on self-reported medical history)
Who cannot join
- Myocardial Infarction
- Stroke
- Current or planned treatment with a GLP-1 RA
- Previous hypersensitivity to or intolerance of GLP-1 RA therapy
- Severe hypoglycaemia within the last six months or during run-in
- Symptomatic hypoglycaemia within the last month
Show all 19Show fewer
- Currently under consideration to commence insulin
- Severe heart failure (NYHA class 4)
- Current or planned renal replacement therapy
- Unwilling to complete regular follow-up assessments
- Ongoing treatment for cancer or diagnosis with cancer (excluding non-melanoma skin cancer) in the last 2 years
- Type 1 or other type of diabetes (e.g. MODY)
- History of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
- Currently breastfeeding or pregnant, or planning a pregnancy
- Any serious illness which is likely to limit survival or active participation for at least 5 years
- Current participation in a clinical trial with an unlicensed investigational medicinal product used to treat diabetes
- For participants taking thyroxine, lack of agreement to arrange a thyroid function test in the next 3 months and agree to regular testing throughout the trial
- Non-adherence to run-in treatment (i.e. reports taking the run-in tablets 'Never' or 'Only occasionally')
- Their doctor does not wish them to be randomised
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical Trial Service Unit and Epidemiological Studies Unit
Oxford
About this study
ASCEND PLUS is testing whether, for people with type 2 diabetes who have not previously had a heart attack or stroke, regularly taking a tablet called semaglutide can safely help to reduce heart attacks, strokes, mini-strokes, the need for any procedures to unblock or bypass an artery to their heart, and the chance of dying because of vascular problems.
Read the detailed description
ASCEND PLUS aims to assess the effects of the GLP1 receptor agonist, oral semaglutide, on major adverse cardiovascular events in people with type 2 diabetes who have not previously suffered a heart attack or stroke. The study will be conducted using novel, streamlined methodology. Participants will be identified from centrally held routinely collected NHS healthcare datasets and invited to join the trial. There will be no physical sites, and all interactions with participants will be conducted directly using innovative patient-centred web-based technology, supplemented by telephone, video call contact and mailed letters.
Study treatment will be mailed to participants. Information regarding serious adverse events and study outcomes relevant to patients with type 2 diabetes mellitus will be collected by regular linkage to UK National Health Service health records both during the scheduled treatment period and for the subsequent 20 years' long term follow-up after the scheduled treatment period.
The trial design includes an active run-in phase, prior to randomisation, during which participants will be asked to take 4-weeks of active 3mg oral semaglutide followed by 4 to 8-weeks of active 7mg oral semaglutide daily.
Participants who are randomised will be allocated to receive either 14mg oral semaglutide or matching placebo daily during the scheduled treatment period. There will be the opportunity to reduce the dose to 7mg or matching placebo if required.
The scheduled treatment period, during which participants are requested to take the study treatment and complete follow-up assessments, is anticipated to continue until the required number of participants has experienced a primary outcome following randomisation. This is expected to occur at a median of approximately 5 years after randomisation.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Semaglutide Oral Tablet, Placebo oral tablet
- 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.
Semaglutide Oral TabletDrug
Oral semaglutide 14mg daily (option to reduce to 7mg daily)
Placebo oral tabletDrug
Placebo oral semaglutide
| Study group | Role | What they receive |
|---|---|---|
| Oral semaglutide | Active comparator | 14mg daily (option to reduce to 7mg daily) Receives: Drug: Semaglutide Oral Tablet |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to the first occurrence of a Major Adverse Cardiovascular Events (MACE+)
MACE+ is an expanded composite, defined as:
- Death from cardiovascular disease
- Non-fatal myocardial infarction
- Non-fatal stroke
- Transient ischaemic attack
- Coronary revascularisation
Measured: Scheduled treatment period (anticipated median follow-up period of 5-years)
Secondary outcomes (1)
Time to the first occurrence of a Major Adverse Cardiovascular Events (MACE)
MACE is a composite, defined as:
- Death from cardiovascular disease
- Non-fatal myocardial infarction
- Non-fatal stroke
Measured: Scheduled treatment period (anticipated median follow-up period of 5-years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2022
- Study start13 Mar 2023
- Primary completion17 Aug 2028 (estimated)
- Study completion17 Aug 2048 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by University of OxfordThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised double-blind placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21,296 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Sponsor
- Investigators
- David Preiss, Principal investigator, University of OxfordMarion Mafham, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05441267
- Sponsor's protocol ID
- CTSU_ASCEND-PLUS
- Acronym
- ASCEND PLUS
- Status last verified
- Jun 2026
- First submitted
- 27 Jun 2022
- Last updated
- 23 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Proposals for substudies must be approved by the Steering Committee.
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Cardiovascular Events iN Diabetes Plus
- ClinicalTrials.gov ID
- NCT05441267
- Acronym / sponsor ID
- ASCEND PLUS / CTSU_ASCEND-PLUS
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 21,296 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Novo Nordisk A/S
- Study start
- 13 Mar 2023 (actual)
- Primary completion
- 17 Aug 2028 (estimated)
- Study completion
- 17 Aug 2048 (estimated)
- First posted
- 1 Jul 2022 (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.
ASCEND PLUS is testing whether, for people with type 2 diabetes who have not previously had a heart attack or stroke, regularly taking a tablet called semaglutide can safely help to reduce heart attacks, strokes, mini-strokes, the need for any procedures to unblock or bypass an artery to their heart, and the chance of dying because of vascular problems.
Detailed description
ASCEND PLUS aims to assess the effects of the GLP1 receptor agonist, oral semaglutide, on major adverse cardiovascular events in people with type 2 diabetes who have not previously suffered a heart attack or stroke. The study will be conducted using novel, streamlined methodology. Participants will be identified from centrally held routinely collected NHS healthcare datasets and invited to join the trial. There will be no physical sites, and all interactions with participants will be conducted directly using innovative patient-centred web-based technology, supplemented by telephone, video call contact and mailed letters.
Study treatment will be mailed to participants. Information regarding serious adverse events and study outcomes relevant to patients with type 2 diabetes mellitus will be collected by regular linkage to UK National Health Service health records both during the scheduled treatment period and for the subsequent 20 years' long term follow-up after the scheduled treatment period.
The trial design includes an active run-in phase, prior to randomisation, during which participants will be asked to take 4-weeks of active 3mg oral semaglutide followed by 4 to 8-weeks of active 7mg oral semaglutide daily.
Participants who are randomised will be allocated to receive either 14mg oral semaglutide or matching placebo daily during the scheduled treatment period. There will be the opportunity to reduce the dose to 7mg or matching placebo if required.
The scheduled treatment period, during which participants are requested to take the study treatment and complete follow-up assessments, is anticipated to continue until the required number of participants has experienced a primary outcome following randomisation. This is expected to occur at a median of approximately 5 years after randomisation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised double-blind placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Oral semaglutide | Active comparator | Drug: Semaglutide Oral Tablet14mg daily (option to reduce to 7mg daily) |
| Placebo | Placebo comparator | Drug: Placebo oral tablet |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adults aged at least 55 years at the time of the Screening assessment
- Type 2 Diabetes Mellitus (based on self-reported medical history)
Key exclusion criteria (19 listed)
- Myocardial Infarction
- Stroke
- Current or planned treatment with a GLP-1 RA
- Previous hypersensitivity to or intolerance of GLP-1 RA therapy
- Severe hypoglycaemia within the last six months or during run-in
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 |
|---|---|---|
| Semaglutide Oral TabletOral semaglutide 14mg daily (option to reduce to 7mg daily) | Drug | Oral semaglutide |
| Placebo oral tabletPlacebo oral semaglutide | Drug | Placebo |
Primary outcome
Time to the first occurrence of a Major Adverse Cardiovascular Events (MACE+)
Time frame: Scheduled treatment period (anticipated median follow-up period of 5-years)
MACE+ is an expanded composite, defined as: * Death from cardiovascular disease * Non-fatal myocardial infarction * Non-fatal stroke * Transient ischaemic attack * Coronary revascularisation
1 secondary outcome
Time to the first occurrence of a Major Adverse Cardiovascular Events (MACE)
Time frame: Scheduled treatment period (anticipated median follow-up period of 5-years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2026.
- Individual participant dataSharing planned: Yes. Proposals for substudies must be approved by the Steering Committee.
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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.
David Preiss principal investigator
University of Oxford
Marion Mafham principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Semaglutide Oral Tablet in people with Diabetes Mellitus, Type 2, run by University of Oxford at 1 site in United Kingdom.
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 2 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Time to the first occurrence of a Major Adverse Cardiovascular Events (MACE+) (time frame: Scheduled treatment period (anticipated median follow-up period of 5-years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jun 2026.