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ASCEND PLUS is a clinical trial being conducted across the UK. About 20,000 people aged 55 or above are being invited to take part in the study. By joining this study you would help us to find out how to protect people with type 2 diabetes from serious heart and circulatory problems and other health problems. The study aims to find out if regularly taking oral semaglutide, a once-daily tablet medication for type 2 diabetes, can help to prevent heart attacks, strokes or mini-strokes, the need for heart artery ‘balloon’ and bypass procedures, and death from heart and circulatory conditions.

If you join the study, you will be asked to take one study tablet each day for about five years in addition to any other medications that you usually take. You will also be asked to complete a questionnaire four times in the first six months, and then once every six months. In total, this will be about 12 questionnaires spread over five years. You can choose whether you complete the questionnaires online yourself or with a research nurse by telephone or video call.

No additional clinic visits or travel are required to take part. Everything happens in your own home, and the study medication will be posted to your address. The first questionnaire takes about 30-40 minutes to complete. Subsequent questionnaires take about 20 minutes each.

During the five-year scheduled treatment period, and for up to 20 years after that, we will collect health data about you from NHS England, other NHS organisations and national registries (unless you contact us to opt out).

After two to three months of trying out the oral semaglutide, participants are given either active oral semaglutide or inactive placebo tablets (which look like the semaglutide tablets but have no active drug in them) for the rest of the study. This is decided by chance by a computer (like tossing a coin). This process is called randomisation. Neither the researchers nor the participants will be aware of which tablet they are taking but the study team can find out if needed.

ASCEND PLUS is testing a medication called oral semaglutide. (‘Oral’ means that it is taken by mouth.)

This medication is approved for use in the UK as a treatment for type 2 diabetes and helps to improve blood sugar control. At higher doses it also used for weight loss.

Semaglutide is similar to a hormone that occurs in the body called glucagon-like peptide-1 (GLP-1). It acts like the hormone to:

  • stimulate the release of insulin by the pancreas after eating, even before blood sugars start to rise
  • help the liver make less sugar (glucose) by inhibiting the release of the hormone glucagon by the pancreas (glucagon causes the liver to release its stored sugar into the bloodstream)
  • reduce the speed at which the stomach empties after eating. This slows sugar absorption into the bloodstream from the food.

These effects all help to control blood sugar in people with type 2 diabetes.

GLP-1 also has other actions in the body. Medications, such as oral semaglutide, which work like the hormone GLP-1 are called ‘GLP-1 receptor agonists’ (or ‘GLP-1-RAs). They help to protect against heart and circulatory problems in people who already have these conditions. Scientists don’t know how these medications help to protect the body’s circulatory system.


By taking part in this trial you will be helping doctors and scientists improve treatment for people with type 2 diabetes. If successful, results from this study might help to prevent many thousands of people around the world from suffering heart attacks, strokes and heart artery stenting or ‘balloon’ and bypass procedures.

No additional clinic visits or travel are required and it will not cost you anything to take part.

You will not be paid for taking part in ASCEND PLUS. 

Oral semaglutide is approved in the UK for treating type 2 diabetes. Most people treated with oral semaglutide do not have any side effects, but about one in ten people who take the tablets experience nausea (feeling sick), vomiting or diarrhoea. If severe, these symptoms can lead to dehydration. These problems usually happen soon after starting the medication or when the dose is increased and they go away with time. Most people who develop these symptoms manage to continue taking oral semaglutide.

If you do feel sick or develop diarrhoea, small changes to your diet can help, for example stopping eating as soon as you start to feel full, and cutting down on fatty foods. We have produced a list of tips to help with side-effects. You can also contact the ASCEND PLUS team

If you join the study, the study treatment may rapidly improve your blood sugar control. Good blood sugar control helps to protect against eye disease caused by diabetes in the longer term, but fast improvements in blood sugar control may lead to a temporary worsening of diabetic eye disease in some patients. It is therefore important to attend your NHS retinal screening appointments as part of your regular diabetes treatment.

Women who are pregnant, planning a pregnancy or breastfeeding, should not take part in the trial because oral semaglutide is not recommended during pregnancy or breastfeeding.

If you also take insulin, gliclazide or another ‘sulphonylurea’ tablet then you might experience hypoglycaemia (low blood sugar or a ‘hypo’) when you start taking oral semaglutide. Sulphonylurea’ tablets include:

  • Gliclazide (Diamicron®, Dacadis®, Vamju®, Ziclaseg® or Zicron®),
  • Glipizide (Minodiab®),
  • Glimepiride (Amaryl®),
  • Glibenclamide (Amglidia®)
  • Tolbutamide (Orinase®).

If you already monitor your blood sugar levels at home, you should continue to do this regularly. This is particularly important for the first few months after starting the study medication.

If you experience unexpected symptoms after joining the study you can contact a study nurse or doctor.



During the study you should continue any diabetes treatments prescribed by your doctor, such as tablet medications or insulin. If you develop low blood sugar (see information about side effects), the study team may suggest an adjustment to your diabetes medication. The study team would discuss this with your GP.

Warfarin – If you take warfarin (an anticoagulant, or blood thinner) you should arrange for your blood ‘INR’ or ‘warfarin level’ level to be checked after starting the study medication, or changing the dose.

Thyroxine – If you take thyroxine, you will need to arrange a blood test for your thyroid function within three months of starting the study medication, even if your levels were previously stable. You should then continue regular monitoring of your thyroid function with your doctor.

The first step in joining ASCEND PLUS is to complete the screening questionnaire. If the answers on your screening questionnaire suggest that the study is suitable for you, we will tell your GP you are planning to join the study and ask them to contact the coordinating centre if they have any concerns.

If we don’t hear about any concerns from your GP, you will be asked to complete the ‘randomisation’ questionnaire.  If you still wish to join the study and your answers to this second questionnaire suggest that the study is suitable for you, you will be ‘randomised’ into the study. This is where the computer selects which treatment you get for the rest of the study and we will tell your GP that you have joined the trial.

We hope you will be able to continue with the study treatment for the full course of the trial.

If you choose to stop the study medication, it would be helpful if you could continue to complete the six-monthly questionnaires. However, you may decide you no longer wish to, or are no longer able to stay in contact with the study team. With your consent at the start of the study, the study scientists can also get information about your health from NHS organisations such as NHS England or other NHS bodies and health registries. If you would like us to stop collecting information about your health from these organisations you can contact the study team at any time. However, data already received by the study would still be analysed to make sure that the study produces reliable results.  

You are free to stop taking part in this study at any time without this having any effect on your future medical care.

Half of the study participants will get tablets containing semaglutide and half will get inactive placebo tablets which look like the semaglutide tablets but have no active drug in them.

At the end of the study we will see how many people in each group suffered a serious heart or circulation problem. These conditions include:

  • heart attacks, strokes or mini strokes (also known as transient ischaemic attacks or TIA)
  • death from heart or circulatory problems
  • the need for a stent or bypass surgery to treat a blocked heart artery.

This information will be analysed to find out if oral semaglutide truly does reduce the risk of people with type 2 diabetes developing these conditions.

Oral semaglutide could also potentially reduce the risk of people with type 2 diabetes from developing other health problems related to diabetes, such as kidney disease and long-term memory problems including dementia. The ASCEND PLUS research team will investigate this.

We will send a summary of the trial results to participants and their GPs at the end of the trial. The trial results will be also available on this website.

ASCEND PLUS is coordinated and sponsored by the University of Oxford, and run with support from the National Institute for Health and Care Research. NHS research staff from across the UK are helping to run the study.

Novo Nordisk produces oral semaglutide and is providing the treatment for the study free of charge. Novo Nordisk has given a grant to the University of Oxford to help with the cost of running of the study but is not directly involved with either coordinating the study or analysing the results.