efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes mellitus treated with insulin

Conditions: Diabetes; Diabetes Mellitus, Type 2

Summary: this trial is conducted globally. the aim of the trial is to investigate the efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes mellitus treated with insulin. all subjects should continue their pre-trial insulin therapy (basal, basal-bolus or premixed regimen including combinations of soluble insulins) throughout the trial. subjects treated with metformin in addition to insulin treatment must continue their metformin treatment throughout the entire trial.


Eligibility criteria:
inclusion criteria: - informed consent obtained before any trial-related activities. trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. - male or female, age above or equal to 18 years at the time of signing informed consent. for japan only: male or female, age above or equal to 20 years at the time of signing informed consent. - diagnosed with type 2 diabetes mellitus 90 days or more prior to the day of screening. - hba1c (glycosylated haemoglobin) of 7.0-9.5% (53-80 mmol/mol) (both inclusive). - stable treatment with one of the following insulin regimens (minimum 10 iu/day) 90 or more days prior to the day of screening. maximum 20% change in total daily dose is acceptable: (1) basal insulin alone or (2) basal and bolus insulin in any combination or (3) premixed insulin including combinations of soluble insulins exclusion criteria: - female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice). for greece only: adequate contraceptive measures are defined as combined hormonal contraception (containing oestrogen and progesterone), which suppress ovulation (oral, intravaginal, percutaneous), progesterone-only hormonal contraception which suppress ovulation (oral, injectable, implantable), intrauterine device, hormone-releasing intrauterine system, bilateral tubal occlusion, partner with vasectomy, sexual abstinence. for japan only: adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives. for canada only: adequate contraceptive measures are defined as combined hormonal contraception (containing oestrogen and progesterone), which suppress ovulation (oral, intravaginal, percutaneous), progesterone-only hormonal contraception which suppress ovulation (oral, injectable, implantable), intrauterine device, hormone-releasing intrauterine system, bilateral tubal occlusion, partner with vasectomy, sexual abstinence - any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol. - family or personal history of multiple endocrine neoplasia type 2 (men 2) or medullary thyroid carcinoma (mtc). - history of pancreatitis (acute or chronic). - history of major surgical procedures involving the stomach and potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery). - any of the following: myocardial infarction (mi), stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation. - classified as being in new york heart association (nyha) class iv. - planned coronary, carotid or peripheral artery revascularisation known on the day of screening. - renal impairment defined as estimated glomerular filtration rate (egfr) less than 60 ml/min/1.73 m\^2 as per chronic kidney disease epidemiology collaboration formula (ckd-epi). - treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. an exception is short-term change of insulin treatment for acute illness for a total of 14 days or less. - known hypoglycaemic unawareness according to clarke's questionnaire. - proliferative retinopathy or maculopathy requiring acute treatment. verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation. - history or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ). - subjects with alanine aminotransferase (alt) more than 2.5 x upper normal limit (unl).