Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin
Condition: Diabetes; Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: semaglutide; semaglutide; semaglutide; placebo
Intervention description: Oral semaglutide administered once-daily for 52 weeks as an add-on to the subjects' pre-trial insulin treatment; Oral semaglutide (3 mg followed by 7 mg) administered once-daily for 52 weeks as an add-on to the subjects' pre-trial insulin treatment; Oral semaglutide (3 mg followed by 7 mg and finally 14 mg) administered once-daily for 52 weeks as an add-on to the subjects' pre-trial insulin treatment; Oral semaglutide placebo administered once-daily for 52 weeks as an add-on to the subjects' pre-trial insulin treatment
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 731.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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).