Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus.
Condition: Diabetes; Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: semaglutide; sitagliptin
Intervention description: Oral administration once-daily.; Oral administration once-daily.
Intervention MeSH terms: Sitagliptin Phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 504.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This trial is globally conducted. The aim of this trial is to investigate Efficacy and Safety
      of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation versus
      Sitagliptin in Subjects with Type 2 Diabetes Mellitus.
    

Eligibility criteria:

        Inclusion Criteria:

        Main phase (the inclusion criteria for the main phase are not reassessed for the extension
        phase):

          -  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 Korea only: Male or female, age above or equal to 19 years at the time of
             signing informed consent

          -  Diagnosed with type 2 diabetes mellitus for at least 90 days prior to day of screening

          -  HbA1c (glycosylated haemoglobin) 7.5-9.5% (58-80 mmol/mol) (both inclusive)

          -  Treatment target of HbA1c below 7.0% (53 mmol/mol), as judged by the investigator

          -  Stable daily dose(s) of 1-2 of the following anti-diabetic drugs within 90 days prior
             to the day of screening:

          -  Metformin (equal or above 1500 mg or maximum tolerated dose as documented in the
             subject medical record)

          -  Sulfonylureas (equal or above half of the maximum approved dose according to local
             label or maximum tolerated dose as documented in subject medical record)

          -  Sodium glucose co-transporter 2 inhibitors

          -  Thiazolidinediones (equal or above half of the maximum approved dose according to
             local label or maximum tolerated dose as documented in subject medical record)

        Extension phase:

          -  Informed consent for the extension phase obtained before any trial-related activities
             for the extension phase.

          -  On randomised treatment with or without rescue medication at week 52.

        Exclusion Criteria:

        Main phase (the exclusion criteria for the main phase are not reassessed for the extension
        phase):

          -  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 certain
             specific countries: Additional specific requirements apply

          -  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 or Medullary Thyroid
             Carcinoma

          -  History of pancreatitis (acute or chronic)

          -  History of major surgical procedures involving the stomach potentially affecting
             absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy,
             gastric bypass surgery)

          -  Any of the following: myocardial infarction, stroke or hospitalisation for unstable
             angina or transient ischaemic attack within the past 180 days prior to the day of
             screening and randomisation

          -  Subjects presently classified as being in New York Heart Association Class IV

          -  Planned coronary, carotid or peripheral artery revascularisation known on the day of
             screening

          -  Subjects with alanine aminotransferase above 2.5 x upper normal limit

          -  Renal impairment defined as Estimated Glomerular Filtration rate 60 mL/min/1.73 m^2 as
             per Chronic Kidney Disease Epidemiology Collaboration formula

          -  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 insulin treatment for acute illness for a total of below or
             equal to 14 days

          -  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)

          -  History of diabetic ketoacidosis

        Extension phase: There are no new exclusion criteria for the extension phase