ASCEND PLUS is a national randomised controlled trial designed to investigate the effects of oral semaglutide on major adverse cardiovascular events and other complications among patients with type 2 diabetes but no history of myocardial infarction or stroke. The study aims to recruit 20,000 such patients in the UK. ASCEND PLUS is coordinated by the Clinical Trial Service Unit part of Oxford Population Health and is sponsored by the University of Oxford. Patients with type 1 diabetes, and women who are breastfeeding, pregnant or planning a pregnancy are not eligible to join the trial.
During the study, participants are asked to continue their usual diabetes therapy and any other medication prescribed by you or other doctors. If it is necessary to commence a GLP-1 receptor agonist as part of your patient’s usual diabetes treatment, then the ASCEND PLUS team should be informed and the randomised study treatment will be discontinued. You patient will continue the trial follow-up procedures.
Oral semaglutide does not interact with any of the major cytochrome P450 isoforms, indicating a low likelihood for drug-drug interactions. Oral semaglutide does not appear to affect the metabolism of warfarin, however regular monitoring of INR is recommended for those on warfarin after starting the treatment. If your patient reported warfarin use in their screening questionnaire, we have asked them to arrange this. It is important that participants taking thyroxine continue to undergo regular checks of their thyroid function tests.
Oral semaglutide causes nausea and diarrhoea in about one in ten patients. This usually resolves over time, and dietary changes can help. Severe gastrointestinal side effects may rarely cause dehydration.
Co-administration with insulin and/or sulphonylurea therapy may increase the risk of hypoglycaemia. If your patient reports symptomatic hypoglycaemia, please consider a reduction in sulphonylurea or insulin dose. You can contact the ASCEND PLUS team for advice.
During follow-up we may ask you for confirmation of any significant events which cannot be readily identified by linkage to NHS records (e.g. transient ischaemic attack).
Further information about oral semaglutide can be found in the current summary of product characteristics. If you would like to discuss any aspect of the study please contact the ASCEND PLUS team.