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
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
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- 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.