Efficacy and Safety of Semaglutide Versus Canagliflozin as add-on to Metformin in Subjects With Type 2 Diabetes
Condition: Diabetes; Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Semaglutide; Canagliflozin; Placebo (canagliflozin); Placebo (semaglutide)
Intervention description: Following a dose escalation phase of 8 weeks, semaglutide 1.0 mg once-weekly(administered subcutaneously, s.c., under the skin) and canagliflozin placebo once-daily (administered orally, as a tablet). Subjects will continue on their pre-trial daily dose of metformin.; Following a dose escalation phase of 8 weeks, canagliflozin 300 mg once-daily (administered orally, as a tablet) and semaglutide placebo (administered subcutaneously, s.c., under the skin). Subjects will continue on their pre-trial daily dose of metformin.; Following a dose escalation phase of 8 weeks, semaglutide 1.0 mg once-weekly(administered subcutaneously, s.c., under the skin) and canagliflozin placebo once-daily (administered orally, as a tablet). Subjects will continue on their pre-trial daily dose of metformin.; Following a dose escalation phase of 8 weeks, canagliflozin 300 mg once-daily (administered orally, as a tablet) and semaglutide placebo (administered subcutaneously, s.c., under the skin). Subjects will continue on their pre-trial daily dose of metformin.
Intervention MeSH terms: Canagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 788.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This trial is conducted in Africa, Asia, Europe, North and South America. The aim of the
      trial is to compare the effect of once-weekly (OW) dosing of subcutaneous semaglutide (1.0
      mg) versus once-daily dosing of oral canagliflozin (300 mg) on glycaemic control in subjects
      with type 2 diabetes (T2D) on a background treatment of metformin
    

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 equal to
        or above18 years at the time of signing informed consent - Diagnosed with type 2 diabetes
        mellitus (T2D) - HbA1c of 7.0-10.5% (53-91 mmol/mol, both inclusive) - Stable daily dose of
        metformin (equal to or above1500 mg or maximum tolerated dose as documented in the subject
        medical record and in compliance with current local label) for at least 90 days prior to
        the day of screening Exclusion Criteria: - Known or suspected hypersensitivity to trial
        product(s) or related products - Previous participation in this trial. Participation is
        defined as signed informed consent - 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) -
        Participation in any clinical trial of an approved or non-approved investigational
        medicinal product within 90 days prior to the day of screening - Any disorder which in the
        investigator's opinion might jeopardise subject's safety or compliance with the protocol -
        Subject with alanine aminotransferase (ALT) above 2.5 x upper normal limit (UNL) - 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 (DKA) - Any of the following: myocardial
        infarction (MI), 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 (NYHA) Class IV - Planned coronary, carotid or
        peripheral artery revascularisation known on the day of screening - Renal impairment
        measured as eGFR below 60 ml/min/1.73 m^2 as defined by Kidney Disease Improving global
        outcomes (KDIGO 2012) classification using isotope dilution mass spectrometry (IDMS) for
        serum creatinine measured at screening - 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 - 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 - Medical history of diabetes-related lower limb
        amputations or signs of critical lower limb ischemia, (e.g. skin ulcer, osteomyelitis, or
        gangrene) within the last 26 weeks prior to screening