Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin

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).