Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to SGLT-2i in Subjects With Type 2 Diabetes Mellitus
Condition: Diabetes; Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Semaglutide; Placebo
Intervention description: Semaglutide, gradually increased to 1.0 mg, injected once weekly under the skin (subcutaneously, s.c.) for 30 weeks; Semaglutide placebo, gradually increased to 1.0 mg, injected once weekly under the skin (subcutaneously, s.c.) for 30 weeks
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 302.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This trial is conducted in Asia, Europe and North America. The aim of the trial is to compare
      the effect of semaglutide s.c. 1.0 mg once-weekly versus placebo as add-on to sodium glucose
      co-transporter-2 inhibitor (SGLT-2i) monotherapy or in combination with either metformin or
      sulfonylurea on glycaemic control after 30 weeks of treatment in subjects with type 2
      diabetes. Subjects will remain on their pre-trial medication.
    

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, above or equal to 18 years at the time of signing informed consent.
             For Japan only: Male or female, age equal to or above 20 years at the time of signing
             informed consent

          -  Diagnosed with type 2 diabetes mellitus

          -  HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive)

          -  Stable dose of an SGLT-2 inhibitor as monotherapy or in combination (including
             fixed-dose drug combination) with a stable dose of metformin (equal to or above 1500
             mg or maximum tolerated dose) or a SU for at least 90 days prior to the day of
             screening. All medications in compliance with current local label

        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)

          -  Any disorder which in the investigator's opinion might jeopardise subject's safety or
             compliance with the protocol

          -  Treatment with any medication for the indication of diabetes or obesity other than
             stated in the inclusion criteria within the past 90 days prior to the day of
             screening. However, short term insulin treatment for a maximum of 14 days prior to the
             day of screening is allowed

          -  Subjects with alanine aminotransferase above 2.5 x upper normal limit

          -  Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid
             carcinoma. Family is defined as a first degree relative

          -  History or presence of pancreatitis (acute or chronic)

          -  History of diabetic ketoacidosis

          -  Any of the following: myocardial infarction, stroke, hospitalization for unstable
             angina or transient ischaemic attack within the past 180 days prior to the day of
             screening

          -  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

          -  Renal impairment measured as estimated Glomerular Filtration Rate value of eGFR below
             60 ml/min/1.73 m^2 as defined by KDIGO 2012 classification using isotope dilution mass
             spectrometry for serum creatinine measured at screening

          -  Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus
             photography or dilated fundoscopy performed within the past 90 days prior to
             randomisation

          -  Presence or history of malignant neoplasms within the past 5 years prior to the day of
             screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed