Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief 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
Interventions
DRUGSemaglutide
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.
DRUGCanagliflozin
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.
DRUGPlacebo (canagliflozin)
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.
DRUGPlacebo (semaglutide)
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.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c | Week 0, week 52 | Change from baseline (week 0) to week 52 in HbA1c (glycosylated haemoglobin) was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first; and 'In-trial' observation period which started at the date of randomisation and include the period after initiation of rescue medication and/or premature trial product discontinuation, if any and ended at the last contact, withdrawal of consent or death, whichever came first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Fat Mass (kg) | Week 0, week 52 | Change from baseline (week 0) to week 52 in total fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in FPG (Fasting Plasma Glucose) | Week 0, week 52 | Change from baseline (week 0) to week 52 in FPG was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in SMPG (Self-measured Plasma Glucose)- Mean 7-point Profile | Week 0, week 52 | Change from baseline (week 0) to week 52 in SMPG- mean 7-point profile was evaluated. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in SMPG- Mean Postprandial Increment Over All Meals | Week 0, week 52 | Change from baseline (week 0) to week 52 in SMPG- mean postprandial increment over all meals was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in Fasting Total Cholesterol | Week 0, week 52 | Change from baseline (week 0) to week 52 in fasting total cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Percentage Change in Total Fat Mass (%) | Week 0, week 52 | Change from baseline (week 0) to week 52 in total fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in Fasting LDL-cholesterol | Week 0, week 52 | Change from baseline (week 0) to week 52 in fasting low-density lipoprotein (LDL) cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in Fasting HDL-cholesterol | Week 0, week 52 | Change from baseline (week 0) to week 52 in fasting high-density lipoprotein (HDL) cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in Fasting Triglycerides | Week 0, week 52 | Change from baseline (week 0) to week 52 in fasting triglycerides (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) | Week 0, week 52 | Change from baseline (week 0) to week 52 in systolic blood pressure and diastolic blood pressure. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Percentage Change in Body Weight (%) | Week 0, week 52 | Change from baseline (week 0) to week 52 in body weight was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in Body Mass Index (BMI) | Week 0, week 52 | Change from baseline (week 0) to week 52 in BMI was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in Waist Circumference | Week 0, week 52 | Change from baseline (week 0) to week 52 in waist circumference was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in Total Lean Mass (kg) | Week 0, week 52 | Change from baseline (week 0) to week 52 in total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Percentage Change in Total Lean Mass (%) | Week 0, week 52 | Change from baseline (week 0) to week 52 in total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in Visceral Fat Mass (kg) | Week 0, week 52 | Change from baseline (week 0) to week 52 in visceral fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Percentage Change in Visceral Fat Mass (%) | Week 0, week 52 | Change from baseline (week 0) to week 52 in visceral fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in Ratio Between Total Fat Mass and Total Lean Mass | Week 0, week 52 | Change from baseline (week 0) to week 52 in ratio between total fat mass and total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no) | Week 52 | Percentage of participants who achieved HbA1c \< 7.0% (53 millimoles per mole \[mmol/mol\]), ADA target (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no) | Week 52 | Percentage of participants who achieved HbA1c ≤ 6.5% (48 mmol/mol), AACE target (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Participants Who Achieved HbA1c Reduction ≥1% (Yes/no) | Week 0, week 52 | Percentage of participants who achieved ≥1% reduction of baseline HbA1c (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Participants Who Achieved Weight Loss ≥3% (Yes/no) | Week 0, week 52 | Percentage of participants losing ≥3% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Participants Who Achieved Weight Loss ≥5% (Yes/no) | Week 0, week 52 | Percentage of participants losing ≥5% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Participants Who Achieved Weight Loss ≥10% (Yes/no) | Week 0, week 52 | Percentage of participants losing ≥10% of baseline body weight is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/no) | Week 0, week 52 | Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value \<3.1 mmol/L (56 milligrams per deciliter \[mg/dL\]) with symptoms consistent with hypoglycaemia. Percentage of participants who achieved HbA1c below 7.0% (53 mmol/mol) without severe or blood glucose confirmed symptomatic hypoglycaemia episodes and no weight gain (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no) | Week 0, week 52 | Percentage of participants who achieved ≥1% reduction of baseline HbA1c and losing ≥3% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no) | Week 0, week 52 | Percentage of participants who achieved ≥1% reduction of baseline HbA1c and losing ≥5% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no) | Week 0, week 52 | Percentage of participants who achieved ≥1% reduction of baseline HbA1c and losing ≥10% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Total Number of Treatment Emergent Adverse Events (TEAEs) | Weeks 0-57 | A TEAE is defined as an adverse event with onset in the on-treatment observation period (which started at the date of first dose of trial product and included the period after initiation of rescue medication, if any and excluded the period after premature trial product discontinuation, if any. TEAEs assessed up to approximately 57 weeks is presented. |
| Change in Haematological Parameter- Haemoglobin | Week 0, week 52 | Change from baseline (week 0) to week 52 in haemoglobin (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Haematological Parameter- Haematocrit | Week 0, week 52 | Change from baseline (week 0) to week 52 in haematocrit (%) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Haematological Parameter- Erythrocytes | Week 0, week 52 | Change from baseline (week 0) to week 52 in erythrocytes (10\^12 cells/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Haematological Parameter- Leukocytes | Week 0, week 52 | Change from baseline (week 0) to week 52 in leukocytes (10\^9 cells/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Haematological Parameter- Thrombocytes | Week 0, week 52 | Change from baseline (week 0) to week 52 in thrombocytes (10\^9 cells/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- Amylase | Week 0, week 52 | Change from baseline (week 0) to week 52 in amylase (units per liter \[U/L\]) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- Lipase | Week 0, week 52 | Change from baseline (week 0) to week 52 in lipase (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- ALT | Week 0, week 52 | Change from baseline (week 0) to week 52 in alanine aminotransferase (ALT) (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- AST | Week 0, week 52 | Change from baseline (week 0) to week 52 in aspartate aminotransferase (AST) (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- ALP | Week 0, week 52 | Change from baseline (week 0) to week 52 in alkaline phosphatase (ALP) (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- Total Bilirubin | Week 0, week 52 | Change from baseline (week 0) to week 52 in total bilirubin (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- Creatinine | Week 0, week 52 | Change from baseline (week 0) to week 52 in creatinine (micromoles per liter \[umol/L\]) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- eGFR | Week 0, week 52 | Estimated glomerular filtration rate (eGFR) (milliliters per minute per 1.73 square meters \[mL/min/1.73m\^2\])is calculated using the equation from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Change from baseline (week 0) to week 52 in eGFR is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- Albumin | Week 0, week 52 | Change from baseline (week 0) to week 52 in albumin (g/dL) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- Calcium | Week 0, week 52 | Change from baseline (week 0) to week 52 in calcium (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- Potassium | Week 0, week 52 | Change from baseline (week 0) to week 52 in potassium (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Biochemistry Parameter- Sodium | Week 0, week 52 | Change from baseline (week 0) to week 52 in sodium (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Calcitonin | Week 0, week 52 | Change from baseline (week 0) to week 52 in calcitonin (nanograms per liter) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Pulse | Week 0, week 52 | Change from baseline (week 0) to week 52 in pulse is presented based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in ECG | Week 0, week 52 | The electrocardiogram (ECG) was assessed by the investigator at baseline (week 0) and week 52 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline and week 52 were presented. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Physical Examination | Week -2, week 52 | Physical examination parameters are categorised as general appearance; nervous system (central and peripheral); cardiovascular system; gastrointestinal system; skin; respiratory system; lymph node palpation; thyroid gland; left foot; right foot; left leg and right leg. The number of participants assessed as normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) at baseline (week -2) and week 52 is presented based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Eye Examination | Week 0, week 52 | Fundus photography or a dilated fundoscopy was performed by the investigator at baseline (week 0) and week 52. The results of the examination were interpreted for each eye (left/right) are categorised as normal, abnormal NCS or abnormal CS. Number of participants in each category at baseline and week 52 were presented. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Total Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-57 | Hypoglycaemic episodes defined as treatment-emergent if the onset of the episode occurs within the on-treatment observation period. Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
| Change in Body Weight (kg) | Week 0, week 52 | Change from baseline (week 0) to week 52 in body weight was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first. |
| Change in Short Form 36 Health Survey (SF-36): Sub-domains | Week 0, week 52 | SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline (week 0) to week 52 in the sub-domain scores is presented. A positive change score indicate an improvement since baseline. Results are based on the 'on-treatment without rescue medication' observation period. |
| Change in SF-36: Physical Component Summary (PCS) | Week 0, week 52 | Change from baseline (week 0) to week 52 in short form 36 v2.0 acute domain PCS. SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. It consists of 2 component summary measures that further summarize 8 health domain scales. The PCS measure is derived from domain scales of physical functioning, role-physical, bodily pain, and general health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline. Results are based on the 'on-treatment without rescue medication' observation period. |
| Change in SF-36: Mental Component Summary (MCS) | Week 0, week 52 | Change from baseline (week 0) to week 52 in short form 36 v2.0 acute domain MCS. SF- 36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The MCS measure is derived from domain scales of vitality, social functioning, role emotional and mental health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline. Results are based on the 'on-treatment without rescue medication' observation period. |
| Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | Week 0, week 52 | Change from baseline (week 0) in DTSQ was evaluated at week 52. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of high blood sugars and low blood sugars, respectively. Thus, lower scores indicate a perception of blood glucose levels being none of the time unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the 'on-treatment without rescue medication' observation period. |
| Change in Control of Eating Questionnaire (CoEQ): Domains | Week 0, week 52 | The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control', 'craving for sweet', 'craving for savoury' and 'positive mood'. The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the 'on-treatment without rescue medication' observation period. |
| Change in CoEQ: Individual Items | Week 0, week 52 | The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control', 'craving for sweet', 'craving for savoury' and 'positive mood'. The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the 'on-treatment without rescue medication' observation period. |
| Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-57 | Number of participants with treatment emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes. Hypoglycaemic episodes defined as treatment-emergent if the onset of the episode occurs within the on-treatment observation period. Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any. |
Countries
Argentina, Brazil, Canada, India, Ireland, Italy, Lebanon, Malaysia, Mexico, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The trial was conducted at 115 sites in Argentina (5), Brazil (2), Canada (8), India (10), Ireland (4), Lebanon (5), Malaysia (5), Mexico (2), Sweden (5), United Kingdom (11) and United States (58).
Pre-assignment details
Study design: Body composition (sub-study) was measured using dual x-ray absorptiometry (DXA) scans in a planned subset of randomised participants.
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide + Canagliflozin Placebo Participants received s.c. injection of semaglutide once-weekly for 52 weeks: 0.25 milligrams (mg) during 0-4 weeks followed by 0.5 mg during 5-8 weeks and then 1.0 mg during 9-52 weeks. Participants also received placebo matched to canagliflozin tablet once-daily for 52 weeks. | 394 |
| Canagliflozin + Semaglutide Placebo Participants received canagliflozin tablet once-daily orally for 52 weeks: 100 mg tablet during 0-8 weeks followed by 300 mg tablet during 9-52 weeks. Participants also received placebo matched to semaglutide s.c. injection once-weekly for 52 weeks. | 394 |
| Total | 788 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 7 | 8 |
| Overall Study | Withdrawal by Subject | 19 | 14 |
Baseline characteristics
| Characteristic | Semaglutide + Canagliflozin Placebo | Canagliflozin + Semaglutide Placebo | Total |
|---|---|---|---|
| Age, Continuous | 55.7 Years STANDARD_DEVIATION 11.1 | 57.5 Years STANDARD_DEVIATION 10.7 | 56.6 Years STANDARD_DEVIATION 10.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 156 Participants | 137 Participants | 293 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 238 Participants | 257 Participants | 495 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HbA1c | 8.3 Percentage (%) of HbA1c STANDARD_DEVIATION 1 | 8.2 Percentage (%) of HbA1c STANDARD_DEVIATION 1 | 8.3 Percentage (%) of HbA1c STANDARD_DEVIATION 1 |
| Race/Ethnicity, Customized Race : American Indian or Alaska native | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Race : Asian | 62 Participants | 63 Participants | 125 Participants |
| Race/Ethnicity, Customized Race : Black or African American | 28 Participants | 30 Participants | 58 Participants |
| Race/Ethnicity, Customized Race : Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race : Not Applicable | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race : Other | 6 Participants | 7 Participants | 13 Participants |
| Race/Ethnicity, Customized Race : White | 297 Participants | 290 Participants | 587 Participants |
| Sex: Female, Male Female | 171 Participants | 193 Participants | 364 Participants |
| Sex: Female, Male Male | 223 Participants | 201 Participants | 424 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 392 | 0 / 394 |
| other Total, other adverse events | 185 / 392 | 120 / 394 |
| serious Total, serious adverse events | 18 / 392 | 21 / 394 |
Outcome results
Primary
Change in HbA1c
Change from baseline (week 0) to week 52 in HbA1c (glycosylated haemoglobin) was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first; and 'In-trial' observation period which started at the date of randomisation and include the period after initiation of rescue medication and/or premature trial product discontinuation, if any and ended at the last contact, withdrawal of consent or death, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in HbA1c | On-treatment without rescue medication | -1.7 Percentage (%) of HbA1c | Standard Deviation 1.1 |
| Semaglutide + Canagliflozin Placebo | Change in HbA1c | In-trial | -1.5 Percentage (%) of HbA1c | Standard Deviation 1.3 |
| Canagliflozin + Semaglutide Placebo | Change in HbA1c | On-treatment without rescue medication | -1.0 Percentage (%) of HbA1c | Standard Deviation 1 |
| Canagliflozin + Semaglutide Placebo | Change in HbA1c | In-trial | -1.0 Percentage (%) of HbA1c | Standard Deviation 1.1 |
Comparison: The responses were analysed using an analysis of covariance (ANCOVA) with treatment, region and stratification factor as fixed factors and baseline value as covariate. Before analysis, missing data were multiple imputed using observed data from participants within the same group defined by randomised treatment, using a regression model including region and stratification factor as categorical effects and data from baseline and all previous visits as covariates.p-value: <0.000195% CI: [-0.65, -0.33]ANCOVA
Comparison: The responses were analysed using an ANCOVA with treatment, region and stratification factor as fixed factors and baseline value as covariate. Before analysis, missing data were multiple imputed using observed data from participants within the same group defined by randomised treatment, using a regression model including region and stratification factor as categorical effects and data from baseline and all previous visits as covariates.p-value: <0.000195% CI: [-0.65, -0.33]ANCOVA
Secondary
Change in Biochemistry Parameter- Albumin
Change from baseline (week 0) to week 52 in albumin (g/dL) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- Albumin | 0.99 Ratio of albumin | Geometric Coefficient of Variation 5.4 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- Albumin | 1.00 Ratio of albumin | Geometric Coefficient of Variation 5.2 |
Secondary
Change in Biochemistry Parameter- ALP
Change from baseline (week 0) to week 52 in alkaline phosphatase (ALP) (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- ALP | 0.96 Ratio of ALP | Geometric Coefficient of Variation 19.6 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- ALP | 0.95 Ratio of ALP | Geometric Coefficient of Variation 16.8 |
Secondary
Change in Biochemistry Parameter- ALT
Change from baseline (week 0) to week 52 in alanine aminotransferase (ALT) (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- ALT | 0.79 Ratio of ALT | Geometric Coefficient of Variation 49.5 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- ALT | 0.79 Ratio of ALT | Geometric Coefficient of Variation 45.3 |
Secondary
Change in Biochemistry Parameter- Amylase
Change from baseline (week 0) to week 52 in amylase (units per liter \[U/L\]) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- Amylase | 1.16 Ratio of amylase | Geometric Coefficient of Variation 26.5 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- Amylase | 1.09 Ratio of amylase | Geometric Coefficient of Variation 24.4 |
Secondary
Change in Biochemistry Parameter- AST
Change from baseline (week 0) to week 52 in aspartate aminotransferase (AST) (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- AST | 0.89 Ratio of AST | Geometric Coefficient of Variation 37.5 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- AST | 0.86 Ratio of AST | Geometric Coefficient of Variation 37.4 |
Secondary
Change in Biochemistry Parameter- Calcium
Change from baseline (week 0) to week 52 in calcium (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- Calcium | 1.01 Ratio of calcium | Geometric Coefficient of Variation 4.5 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- Calcium | 1.02 Ratio of calcium | Geometric Coefficient of Variation 4.1 |
Secondary
Change in Biochemistry Parameter- Creatinine
Change from baseline (week 0) to week 52 in creatinine (micromoles per liter \[umol/L\]) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- Creatinine | 1.03 Ratio of creatinine | Geometric Coefficient of Variation 11 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- Creatinine | 1.04 Ratio of creatinine | Geometric Coefficient of Variation 11.9 |
Secondary
Change in Biochemistry Parameter- eGFR
Estimated glomerular filtration rate (eGFR) (milliliters per minute per 1.73 square meters \[mL/min/1.73m\^2\])is calculated using the equation from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Change from baseline (week 0) to week 52 in eGFR is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- eGFR | 0.98 Ratio of eGFR | Geometric Coefficient of Variation 8.4 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- eGFR | 0.96 Ratio of eGFR | Geometric Coefficient of Variation 9.7 |
Secondary
Change in Biochemistry Parameter- Lipase
Change from baseline (week 0) to week 52 in lipase (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- Lipase | 1.25 Ratio of lipase | Geometric Coefficient of Variation 54.5 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- Lipase | 1.01 Ratio of lipase | Geometric Coefficient of Variation 51.5 |
Secondary
Change in Biochemistry Parameter- Potassium
Change from baseline (week 0) to week 52 in potassium (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- Potassium | 1.00 Ratio of potassium | Geometric Coefficient of Variation 9.3 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- Potassium | 1.00 Ratio of potassium | Geometric Coefficient of Variation 8.6 |
Secondary
Change in Biochemistry Parameter- Sodium
Change from baseline (week 0) to week 52 in sodium (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- Sodium | 1.00 Ratio of sodium | Geometric Coefficient of Variation 1.6 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- Sodium | 1.00 Ratio of sodium | Geometric Coefficient of Variation 1.5 |
Secondary
Change in Biochemistry Parameter- Total Bilirubin
Change from baseline (week 0) to week 52 in total bilirubin (U/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Biochemistry Parameter- Total Bilirubin | 1.06 Ratio of total bilirubin | Geometric Coefficient of Variation 32.1 |
| Canagliflozin + Semaglutide Placebo | Change in Biochemistry Parameter- Total Bilirubin | 1.13 Ratio of total bilirubin | Geometric Coefficient of Variation 33.9 |
Secondary
Change in Body Mass Index (BMI)
Change from baseline (week 0) to week 52 in BMI was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Body Mass Index (BMI) | -2.0 Kilogram per square meter (kg/m^2) | Standard Deviation 2 |
| Canagliflozin + Semaglutide Placebo | Change in Body Mass Index (BMI) | -1.5 Kilogram per square meter (kg/m^2) | Standard Deviation 1.4 |
Secondary
Change in Body Weight (kg)
Change from baseline (week 0) to week 52 in body weight was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Body Weight (kg) | -5.7 Kilogram (kg) | Standard Deviation 5.4 |
| Canagliflozin + Semaglutide Placebo | Change in Body Weight (kg) | -4.3 Kilogram (kg) | Standard Deviation 4 |
Secondary
Change in Calcitonin
Change from baseline (week 0) to week 52 in calcitonin (nanograms per liter) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Calcitonin | 1.08 Ratio of calcitonin | Geometric Coefficient of Variation 43.8 |
| Canagliflozin + Semaglutide Placebo | Change in Calcitonin | 1.04 Ratio of calcitonin | Geometric Coefficient of Variation 35.6 |
Secondary
Change in CoEQ: Individual Items
The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control', 'craving for sweet', 'craving for savoury' and 'positive mood'. The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the 'on-treatment without rescue medication' observation period.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | How hungry have you felt | -1.2 Score on a scale | Standard Deviation 2.6 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | How full have you felt | 0.2 Score on a scale | Standard Deviation 2.7 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | How often have you had cravings (last 7 days) | -0.9 Score on a scale | Standard Deviation 2.9 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | How strong have any cravings been | -0.9 Score on a scale | Standard Deviation 2.9 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Difficulty to resist cravings | -0.9 Score on a scale | Standard Deviation 2.9 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Ate in response to cravings | -0.9 Score on a scale | Standard Deviation 2.7 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Difficulty to control eating | -1.5 Score on a scale | Standard Deviation 2.8 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Craving for dairy foods | -0.8 Score on a scale | Standard Deviation 2.9 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Craving for starchy foods | -1.4 Score on a scale | Standard Deviation 2.7 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Desire to eat sweet food | -0.9 Score on a scale | Standard Deviation 3.1 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Craving for chocolate | -0.3 Score on a scale | Standard Deviation 3.1 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Craving for other sweets | -0.6 Score on a scale | Standard Deviation 2.8 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Craving for fruit or fruit juice | -0.6 Score on a scale | Standard Deviation 3 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Felt happy | 0.8 Score on a scale | Standard Deviation 2.5 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Felt contented | 0.8 Score on a scale | Standard Deviation 2.4 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Desire to eat savory food | -1.4 Score on a scale | Standard Deviation 2.6 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Craving for savory foods | -0.9 Score on a scale | Standard Deviation 2.9 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Felt anxious | -0.9 Score on a scale | Standard Deviation 3.1 |
| Semaglutide + Canagliflozin Placebo | Change in CoEQ: Individual Items | Felt alert | 0.2 Score on a scale | Standard Deviation 2.4 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Felt anxious | -0.6 Score on a scale | Standard Deviation 2.7 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | How hungry have you felt | -0.8 Score on a scale | Standard Deviation 2.6 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Craving for chocolate | -0.4 Score on a scale | Standard Deviation 2.9 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | How full have you felt | 0.0 Score on a scale | Standard Deviation 2.7 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Desire to eat savory food | -1.0 Score on a scale | Standard Deviation 2.8 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Craving for other sweets | -0.6 Score on a scale | Standard Deviation 2.8 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | How strong have any cravings been | -1.1 Score on a scale | Standard Deviation 3 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Felt contented | 0.5 Score on a scale | Standard Deviation 2.2 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Difficulty to resist cravings | -0.8 Score on a scale | Standard Deviation 3.2 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Craving for fruit or fruit juice | -0.6 Score on a scale | Standard Deviation 3.2 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Ate in response to cravings | -0.7 Score on a scale | Standard Deviation 3.2 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Felt happy | 0.4 Score on a scale | Standard Deviation 2.3 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Felt alert | 0.0 Score on a scale | Standard Deviation 2.4 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Craving for dairy foods | -0.6 Score on a scale | Standard Deviation 3.1 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | How often have you had cravings (last 7 days) | -1.1 Score on a scale | Standard Deviation 3 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Craving for starchy foods | -1.1 Score on a scale | Standard Deviation 3 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Craving for savory foods | -0.9 Score on a scale | Standard Deviation 2.9 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Difficulty to control eating | -1.2 Score on a scale | Standard Deviation 3 |
| Canagliflozin + Semaglutide Placebo | Change in CoEQ: Individual Items | Desire to eat sweet food | -1.0 Score on a scale | Standard Deviation 2.9 |
Secondary
Change in Control of Eating Questionnaire (CoEQ): Domains
The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control', 'craving for sweet', 'craving for savoury' and 'positive mood'. The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the 'on-treatment without rescue medication' observation period.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Control of Eating Questionnaire (CoEQ): Domains | Craving for sweet | -0.6 Score on a scale | Standard Deviation 2.2 |
| Semaglutide + Canagliflozin Placebo | Change in Control of Eating Questionnaire (CoEQ): Domains | Craving control | 1.0 Score on a scale | Standard Deviation 2.1 |
| Semaglutide + Canagliflozin Placebo | Change in Control of Eating Questionnaire (CoEQ): Domains | Positive mood | 0.7 Score on a scale | Standard Deviation 1.7 |
| Semaglutide + Canagliflozin Placebo | Change in Control of Eating Questionnaire (CoEQ): Domains | Craving for savoury | -1.1 Score on a scale | Standard Deviation 2 |
| Canagliflozin + Semaglutide Placebo | Change in Control of Eating Questionnaire (CoEQ): Domains | Positive mood | 0.4 Score on a scale | Standard Deviation 1.6 |
| Canagliflozin + Semaglutide Placebo | Change in Control of Eating Questionnaire (CoEQ): Domains | Craving control | 1.0 Score on a scale | Standard Deviation 2.5 |
| Canagliflozin + Semaglutide Placebo | Change in Control of Eating Questionnaire (CoEQ): Domains | Craving for savoury | -0.9 Score on a scale | Standard Deviation 2 |
| Canagliflozin + Semaglutide Placebo | Change in Control of Eating Questionnaire (CoEQ): Domains | Craving for sweet | -0.6 Score on a scale | Standard Deviation 2.1 |
Secondary
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately
Change from baseline (week 0) in DTSQ was evaluated at week 52. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of high blood sugars and low blood sugars, respectively. Thus, lower scores indicate a perception of blood glucose levels being none of the time unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the 'on-treatment without rescue medication' observation period.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 3) Feeling of unacceptably low blood sugars | 0.1 Score on a scale | Standard Deviation 1.9 |
| Semaglutide + Canagliflozin Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 5) Flexibility of current treatment | 0.8 Score on a scale | Standard Deviation 1.7 |
| Semaglutide + Canagliflozin Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 8) Satisfaction to continue with present treatment | 1.1 Score on a scale | Standard Deviation 1.8 |
| Semaglutide + Canagliflozin Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 1) Satisfaction with treatment | 1.4 Score on a scale | Standard Deviation 1.6 |
| Semaglutide + Canagliflozin Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 7) Recommending treatment to others | 0.9 Score on a scale | Standard Deviation 1.5 |
| Semaglutide + Canagliflozin Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 4) Convenience of treatment | 0.8 Score on a scale | Standard Deviation 1.8 |
| Semaglutide + Canagliflozin Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 2) Feeling of unacceptably high blood sugars | -2.0 Score on a scale | Standard Deviation 2.2 |
| Semaglutide + Canagliflozin Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | Total treatment satisfaction score | 5.8 Score on a scale | Standard Deviation 7 |
| Semaglutide + Canagliflozin Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 6) Satisfaction with understanding of diabetes | 0.8 Score on a scale | Standard Deviation 1.5 |
| Canagliflozin + Semaglutide Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | Total treatment satisfaction score | 4.8 Score on a scale | Standard Deviation 7.2 |
| Canagliflozin + Semaglutide Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 4) Convenience of treatment | 0.7 Score on a scale | Standard Deviation 1.8 |
| Canagliflozin + Semaglutide Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 1) Satisfaction with treatment | 1.0 Score on a scale | Standard Deviation 1.6 |
| Canagliflozin + Semaglutide Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 2) Feeling of unacceptably high blood sugars | -1.8 Score on a scale | Standard Deviation 2.2 |
| Canagliflozin + Semaglutide Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 5) Flexibility of current treatment | 0.7 Score on a scale | Standard Deviation 1.7 |
| Canagliflozin + Semaglutide Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 6) Satisfaction with understanding of diabetes | 0.6 Score on a scale | Standard Deviation 1.3 |
| Canagliflozin + Semaglutide Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 7) Recommending treatment to others | 0.9 Score on a scale | Standard Deviation 1.5 |
| Canagliflozin + Semaglutide Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 8) Satisfaction to continue with present treatment | 0.8 Score on a scale | Standard Deviation 1.8 |
| Canagliflozin + Semaglutide Placebo | Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately | 3) Feeling of unacceptably low blood sugars | 0.1 Score on a scale | Standard Deviation 1.6 |
Secondary
Change in ECG
The electrocardiogram (ECG) was assessed by the investigator at baseline (week 0) and week 52 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline and week 52 were presented. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in ECG | Abnormal NCS (week 0) | 126 Participants |
| Semaglutide + Canagliflozin Placebo | Change in ECG | Abnormal CS (week 52) | 0 Participants |
| Semaglutide + Canagliflozin Placebo | Change in ECG | Abnormal CS (week 0) | 3 Participants |
| Semaglutide + Canagliflozin Placebo | Change in ECG | Normal (week 52) | 222 Participants |
| Semaglutide + Canagliflozin Placebo | Change in ECG | Normal (week 0) | 263 Participants |
| Semaglutide + Canagliflozin Placebo | Change in ECG | Abnormal NCS (week 52) | 109 Participants |
| Canagliflozin + Semaglutide Placebo | Change in ECG | Abnormal CS (week 52) | 3 Participants |
| Canagliflozin + Semaglutide Placebo | Change in ECG | Abnormal NCS (week 52) | 95 Participants |
| Canagliflozin + Semaglutide Placebo | Change in ECG | Normal (week 52) | 242 Participants |
| Canagliflozin + Semaglutide Placebo | Change in ECG | Normal (week 0) | 277 Participants |
| Canagliflozin + Semaglutide Placebo | Change in ECG | Abnormal CS (week 0) | 0 Participants |
| Canagliflozin + Semaglutide Placebo | Change in ECG | Abnormal NCS (week 0) | 117 Participants |
Secondary
Change in Fasting HDL-cholesterol
Change from baseline (week 0) to week 52 in fasting high-density lipoprotein (HDL) cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Fasting HDL-cholesterol | 1.04 Ratio of HDL-cholesterol | Geometric Coefficient of Variation 13.1 |
| Canagliflozin + Semaglutide Placebo | Change in Fasting HDL-cholesterol | 1.08 Ratio of HDL-cholesterol | Geometric Coefficient of Variation 13.6 |
Secondary
Change in Fasting LDL-cholesterol
Change from baseline (week 0) to week 52 in fasting low-density lipoprotein (LDL) cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Fasting LDL-cholesterol | 0.96 Ratio of LDL-cholesterol | Geometric Coefficient of Variation 32.2 |
| Canagliflozin + Semaglutide Placebo | Change in Fasting LDL-cholesterol | 1.05 Ratio of LDL-cholesterol | Geometric Coefficient of Variation 29 |
Secondary
Change in Fasting Total Cholesterol
Change from baseline (week 0) to week 52 in fasting total cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Fasting Total Cholesterol | 0.96 Ratio of total cholesterol | Geometric Coefficient of Variation 19.3 |
| Canagliflozin + Semaglutide Placebo | Change in Fasting Total Cholesterol | 1.03 Ratio of total cholesterol | Geometric Coefficient of Variation 18.2 |
Secondary
Change in Fasting Triglycerides
Change from baseline (week 0) to week 52 in fasting triglycerides (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Fasting Triglycerides | 0.86 Ratio of triglycerides | Geometric Coefficient of Variation 40.6 |
| Canagliflozin + Semaglutide Placebo | Change in Fasting Triglycerides | 0.92 Ratio of triglycerides | Geometric Coefficient of Variation 38.2 |
Secondary
Change in FPG (Fasting Plasma Glucose)
Change from baseline (week 0) to week 52 in FPG was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in FPG (Fasting Plasma Glucose) | -2.54 Millimoles per liter (mmol/L) | Standard Deviation 2.77 |
| Canagliflozin + Semaglutide Placebo | Change in FPG (Fasting Plasma Glucose) | -2.00 Millimoles per liter (mmol/L) | Standard Deviation 2.53 |
Secondary
Change in Haematological Parameter- Erythrocytes
Change from baseline (week 0) to week 52 in erythrocytes (10\^12 cells/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Haematological Parameter- Erythrocytes | 0.99 Ratio of erythrocytes | Geometric Coefficient of Variation 5.7 |
| Canagliflozin + Semaglutide Placebo | Change in Haematological Parameter- Erythrocytes | 1.04 Ratio of erythrocytes | Geometric Coefficient of Variation 6 |
Secondary
Change in Haematological Parameter- Haematocrit
Change from baseline (week 0) to week 52 in haematocrit (%) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Haematological Parameter- Haematocrit | 0.99 Ratio of haematocrit | Geometric Coefficient of Variation 6.8 |
| Canagliflozin + Semaglutide Placebo | Change in Haematological Parameter- Haematocrit | 1.04 Ratio of haematocrit | Geometric Coefficient of Variation 6.9 |
Secondary
Change in Haematological Parameter- Haemoglobin
Change from baseline (week 0) to week 52 in haemoglobin (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Haematological Parameter- Haemoglobin | 0.99 Ratio of haemoglobin | Geometric Coefficient of Variation 8 |
| Canagliflozin + Semaglutide Placebo | Change in Haematological Parameter- Haemoglobin | 1.05 Ratio of haemoglobin | Geometric Coefficient of Variation 8.5 |
Secondary
Change in Haematological Parameter- Leukocytes
Change from baseline (week 0) to week 52 in leukocytes (10\^9 cells/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Haematological Parameter- Leukocytes | 0.97 Ratio of leukocytes | Geometric Coefficient of Variation 20.3 |
| Canagliflozin + Semaglutide Placebo | Change in Haematological Parameter- Leukocytes | 0.98 Ratio of leukocytes | Geometric Coefficient of Variation 17.5 |
Secondary
Change in Haematological Parameter- Thrombocytes
Change from baseline (week 0) to week 52 in thrombocytes (10\^9 cells/L) is presented as ratio to baseline. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Haematological Parameter- Thrombocytes | 1.04 Ratio of thrombocytes | Geometric Coefficient of Variation 14.4 |
| Canagliflozin + Semaglutide Placebo | Change in Haematological Parameter- Thrombocytes | 1.00 Ratio of thrombocytes | Geometric Coefficient of Variation 15.4 |
Secondary
Change in Physical Examination
Physical examination parameters are categorised as general appearance; nervous system (central and peripheral); cardiovascular system; gastrointestinal system; skin; respiratory system; lymph node palpation; thyroid gland; left foot; right foot; left leg and right leg. The number of participants assessed as normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) at baseline (week -2) and week 52 is presented based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week -2, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Nervous System (week 52) Normal | 303 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Lymph Node Palpation (week 52) Abnormal NCS | 0 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Nervous System (week 52) Abnormal NCS | 21 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Cardiovascular System (week-2) Normal | 376 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Cardiovascular System (week 52) Abnormal CS | 1 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Gastrointestinal System (week -2) Normal | 369 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Nervous System (week 52) Abnormal CS | 2 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right leg (week 52) Abnormal CS | 6 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Gastrointestinal System (week -2) Abnormal NCS | 22 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right foot (week -2) Abnormal CS | 3 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | General Appearance (week -2) Abnormal CS | 1 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right foot (week 52) Normal | 289 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | General Appearance (week 52) Abnormal NCS | 30 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right foot (week 52) Abnormal NCS | 34 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Gastrointestinal System (week -2) Abnormal CS | 1 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right foot (week 52) Abnormal CS | 3 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | General Appearance (week 52) Abnormal CS | 2 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left leg (week -2) Normal | 348 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Nervous System (week -2) Normal | 360 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left leg (week -2) Abnormal NCS | 40 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Gastrointestinal System (week 52) Abnormal NCS | 7 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left leg (week -2) Abnormal CS | 4 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Cardiovascular System (week -2) Abnormal CS | 1 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left leg (week 52) Normal | 300 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Thyroid Gland (week 52) Abnormal NCS | 0 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Gastrointestinal System (week 52) Abnormal CS | 0 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left leg (week 52) Abnormal CS | 4 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right leg (week -2) Normal | 350 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Thyroid Gland (week 52) Abnormal CS | 0 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right leg (week -2) Abnormal NCS | 37 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Nervous System (week -2) Abnormal CS | 5 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right leg (week -2) Abnormal CS | 5 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left foot (week -2) Normal | 343 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right leg (week 52) Normal | 301 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Skin (week -2) Normal | 330 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right leg (week 52) Abnormal NCS | 19 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left foot (week -2) Abnormal NCS | 47 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Gastrointestinal System (week 52) Normal | 319 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Cardiovascular System (week52) Normal | 318 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left foot (week -2) Abnormal CS | 2 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Skin (week 52) Abnormal NCS | 39 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Skin (week -2) Abnormal NCS | 62 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Skin (week 52) Abnormal CS | 1 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left foot (week 52) Normal | 293 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Respiratory System (week -2) Normal | 383 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Skin (week -2) Abnormal CS | 0 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Respiratory System (week -2) Abnormal NCS | 7 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Respiratory System (week -2) Abnormal CS | 2 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left foot (week 52) Abnormal NCS | 32 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Respiratory System (week 52) Normal | 321 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | General Appearance (week 52) Normal | 294 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Respiratory System (week 52) Abnormal NCS | 4 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left foot (week 52) Abnormal CS | 1 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Respiratory System (week 52) Abnormal CS | 1 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Skin (week 52) Normal | 286 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right foot (week -2) Normal | 344 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Lymph Node Palpation (week -2) Abnormal NCS | 1 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Right foot (week -2) Abnormal NCS | 45 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Lymph Node Palpation (week -2) Abnormal CS | 0 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | General Appearance (week -2) Normal | 345 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Lymph Node Palpation (week 52) Normal | 325 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Cardiovascular System (week 52) Abnormal NCS | 7 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | General Appearance (week -2) Abnormal NCS | 46 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Lymph Node Palpation (week 52) Abnormal CS | 0 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Nervous System (week -2) Abnormal NCS | 26 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Thyroid Gland (week -2) Normal | 390 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Cardiovascular System (week -2) Abnormal NCS | 15 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Thyroid Gland (week -2) Abnormal NCS | 2 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Left leg (week 52) Abnormal NCS | 22 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Thyroid Gland (week -2) Abnormal CS | 0 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Lymph Node Palpation (week -2) Normal | 390 Participants |
| Semaglutide + Canagliflozin Placebo | Change in Physical Examination | Thyroid Gland (week 52) Normal | 326 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left leg (week -2) Normal | 358 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | General Appearance (week -2) Abnormal CS | 3 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | General Appearance (week 52) Normal | 304 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | General Appearance (week 52) Abnormal CS | 2 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Nervous System (week 52) Abnormal NCS | 12 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Nervous System (week 52) Abnormal CS | 2 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Cardiovascular System (week-2) Normal | 386 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Cardiovascular System (week -2) Abnormal NCS | 8 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Cardiovascular System (week -2) Abnormal CS | 0 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Cardiovascular System (week52) Normal | 333 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Cardiovascular System (week 52) Abnormal NCS | 6 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Gastrointestinal System (week -2) Normal | 377 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Gastrointestinal System (week 52) Abnormal NCS | 8 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Gastrointestinal System (week 52) Abnormal CS | 0 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Skin (week -2) Normal | 323 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Skin (week -2) Abnormal CS | 2 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Skin (week 52) Normal | 298 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Respiratory System (week -2) Abnormal NCS | 3 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right foot (week -2) Normal | 348 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left leg (week 52) Abnormal CS | 3 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right leg (week 52) Abnormal CS | 3 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | General Appearance (week 52) Abnormal NCS | 33 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Nervous System (week -2) Normal | 370 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Thyroid Gland (week 52) Normal | 337 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Thyroid Gland (week 52) Abnormal NCS | 1 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Thyroid Gland (week 52) Abnormal CS | 0 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left foot (week -2) Normal | 345 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left foot (week -2) Abnormal NCS | 44 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left foot (week -2) Abnormal CS | 5 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left foot (week 52) Normal | 303 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left foot (week 52) Abnormal NCS | 34 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left foot (week 52) Abnormal CS | 2 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | General Appearance (week -2) Normal | 335 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Nervous System (week -2) Abnormal NCS | 21 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Nervous System (week -2) Abnormal CS | 3 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Nervous System (week 52) Normal | 325 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Cardiovascular System (week 52) Abnormal CS | 0 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Gastrointestinal System (week -2) Abnormal NCS | 16 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Gastrointestinal System (week -2) Abnormal CS | 1 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right foot (week -2) Abnormal NCS | 42 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right foot (week -2) Abnormal CS | 4 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right foot (week 52) Normal | 304 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right foot (week 52) Abnormal NCS | 32 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right foot (week 52) Abnormal CS | 3 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | General Appearance (week -2) Abnormal NCS | 56 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left leg (week -2) Abnormal NCS | 30 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left leg (week -2) Abnormal CS | 6 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left leg (week 52) Normal | 314 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Left leg (week 52) Abnormal NCS | 22 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right leg (week -2) Normal | 357 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right leg (week -2) Abnormal NCS | 30 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right leg (week -2) Abnormal CS | 7 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right leg (week 52) Normal | 315 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Right leg (week 52) Abnormal NCS | 21 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Gastrointestinal System (week 52) Normal | 331 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Skin (week -2) Abnormal NCS | 69 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Skin (week 52) Abnormal NCS | 40 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Skin (week 52) Abnormal CS | 1 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Respiratory System (week -2) Normal | 391 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Respiratory System (week -2) Abnormal CS | 0 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Respiratory System (week 52) Normal | 336 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Respiratory System (week 52) Abnormal NCS | 3 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Respiratory System (week 52) Abnormal CS | 0 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Lymph Node Palpation (week -2) Normal | 392 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Lymph Node Palpation (week -2) Abnormal NCS | 2 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Lymph Node Palpation (week -2) Abnormal CS | 0 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Lymph Node Palpation (week 52) Normal | 337 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Lymph Node Palpation (week 52) Abnormal NCS | 0 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Lymph Node Palpation (week 52) Abnormal CS | 0 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Thyroid Gland (week -2) Normal | 390 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Thyroid Gland (week -2) Abnormal NCS | 4 Participants |
| Canagliflozin + Semaglutide Placebo | Change in Physical Examination | Thyroid Gland (week -2) Abnormal CS | 0 Participants |
Secondary
Change in Pulse
Change from baseline (week 0) to week 52 in pulse is presented based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Pulse | 2.7 Beats per minute (beats/min) | Standard Deviation 9.5 |
| Canagliflozin + Semaglutide Placebo | Change in Pulse | -0.6 Beats per minute (beats/min) | Standard Deviation 8.6 |
Secondary
Change in Ratio Between Total Fat Mass and Total Lean Mass
Change from baseline (week 0) to week 52 in ratio between total fat mass and total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Ratio Between Total Fat Mass and Total Lean Mass | -0.04 total fat mass/total lean mass ratio | Standard Deviation 0.08 |
| Canagliflozin + Semaglutide Placebo | Change in Ratio Between Total Fat Mass and Total Lean Mass | -0.03 total fat mass/total lean mass ratio | Standard Deviation 0.07 |
Secondary
Change in SF-36: Mental Component Summary (MCS)
Change from baseline (week 0) to week 52 in short form 36 v2.0 acute domain MCS. SF- 36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The MCS measure is derived from domain scales of vitality, social functioning, role emotional and mental health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline. Results are based on the 'on-treatment without rescue medication' observation period.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in SF-36: Mental Component Summary (MCS) | 1.1 Score on a scale | Standard Deviation 8.8 |
| Canagliflozin + Semaglutide Placebo | Change in SF-36: Mental Component Summary (MCS) | 0.5 Score on a scale | Standard Deviation 8 |
Secondary
Change in SF-36: Physical Component Summary (PCS)
Change from baseline (week 0) to week 52 in short form 36 v2.0 acute domain PCS. SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. It consists of 2 component summary measures that further summarize 8 health domain scales. The PCS measure is derived from domain scales of physical functioning, role-physical, bodily pain, and general health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline. Results are based on the 'on-treatment without rescue medication' observation period.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in SF-36: Physical Component Summary (PCS) | 2.7 Score on a scale | Standard Deviation 6.7 |
| Canagliflozin + Semaglutide Placebo | Change in SF-36: Physical Component Summary (PCS) | 2.9 Score on a scale | Standard Deviation 6.2 |
Secondary
Change in Short Form 36 Health Survey (SF-36): Sub-domains
SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline (week 0) to week 52 in the sub-domain scores is presented. A positive change score indicate an improvement since baseline. Results are based on the 'on-treatment without rescue medication' observation period.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Social functioning | 1.1 Score on a scale | Standard Deviation 8.6 |
| Semaglutide + Canagliflozin Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Role-physical | 1.8 Score on a scale | Standard Deviation 7.3 |
| Semaglutide + Canagliflozin Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Mental health | 1.5 Score on a scale | Standard Deviation 8.3 |
| Semaglutide + Canagliflozin Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | General health | 3.7 Score on a scale | Standard Deviation 7.7 |
| Semaglutide + Canagliflozin Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Bodily pain | 2.5 Score on a scale | Standard Deviation 8.9 |
| Semaglutide + Canagliflozin Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Role-emotional | 0.8 Score on a scale | Standard Deviation 9.2 |
| Semaglutide + Canagliflozin Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Physical Functioning | 1.9 Score on a scale | Standard Deviation 7.1 |
| Semaglutide + Canagliflozin Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Vitality | 3.0 Score on a scale | Standard Deviation 8.2 |
| Canagliflozin + Semaglutide Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Physical Functioning | 2.7 Score on a scale | Standard Deviation 6.7 |
| Canagliflozin + Semaglutide Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Social functioning | 1.1 Score on a scale | Standard Deviation 8 |
| Canagliflozin + Semaglutide Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Vitality | 2.0 Score on a scale | Standard Deviation 8.2 |
| Canagliflozin + Semaglutide Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Mental health | 0.6 Score on a scale | Standard Deviation 8.1 |
| Canagliflozin + Semaglutide Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Role-physical | 2.0 Score on a scale | Standard Deviation 7.1 |
| Canagliflozin + Semaglutide Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Bodily pain | 1.5 Score on a scale | Standard Deviation 8.7 |
| Canagliflozin + Semaglutide Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | General health | 3.5 Score on a scale | Standard Deviation 8.5 |
| Canagliflozin + Semaglutide Placebo | Change in Short Form 36 Health Survey (SF-36): Sub-domains | Role-emotional | 1.2 Score on a scale | Standard Deviation 8.6 |
Secondary
Change in SMPG- Mean Postprandial Increment Over All Meals
Change from baseline (week 0) to week 52 in SMPG- mean postprandial increment over all meals was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in SMPG- Mean Postprandial Increment Over All Meals | -0.6 mmol/L | Standard Deviation 2.1 |
| Canagliflozin + Semaglutide Placebo | Change in SMPG- Mean Postprandial Increment Over All Meals | -0.6 mmol/L | Standard Deviation 2 |
Secondary
Change in SMPG (Self-measured Plasma Glucose)- Mean 7-point Profile
Change from baseline (week 0) to week 52 in SMPG- mean 7-point profile was evaluated. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in SMPG (Self-measured Plasma Glucose)- Mean 7-point Profile | -2.8 mmol/L | Standard Deviation 2.3 |
| Canagliflozin + Semaglutide Placebo | Change in SMPG (Self-measured Plasma Glucose)- Mean 7-point Profile | -1.9 mmol/L | Standard Deviation 2.7 |
Secondary
Change in Total Fat Mass (kg)
Change from baseline (week 0) to week 52 in total fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Dual X-ray absorptiometry (DXA) analysis set comprised of all randomised participants who are included in the body composition sub-study. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Total Fat Mass (kg) | -3.72 kg | Standard Deviation 4.5 |
| Canagliflozin + Semaglutide Placebo | Change in Total Fat Mass (kg) | -2.63 kg | Standard Deviation 3.3 |
Secondary
Change in Total Lean Mass (kg)
Change from baseline (week 0) to week 52 in total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Total Lean Mass (kg) | -2.06 kg | Standard Deviation 2.15 |
| Canagliflozin + Semaglutide Placebo | Change in Total Lean Mass (kg) | -1.53 kg | Standard Deviation 2.21 |
Secondary
Change in Visceral Fat Mass (kg)
Change from baseline (week 0) to week 52 in visceral fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Visceral Fat Mass (kg) | -0.20 kg | Standard Deviation 0.4 |
| Canagliflozin + Semaglutide Placebo | Change in Visceral Fat Mass (kg) | -0.13 kg | Standard Deviation 0.32 |
Secondary
Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure)
Change from baseline (week 0) to week 52 in systolic blood pressure and diastolic blood pressure. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) | Systolic blood pressure | -3.7 Millimeters of mercury (mmHg) | Standard Deviation 14 |
| Semaglutide + Canagliflozin Placebo | Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) | Diastolic blood pressure | -1.2 Millimeters of mercury (mmHg) | Standard Deviation 9.8 |
| Canagliflozin + Semaglutide Placebo | Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) | Diastolic blood pressure | -2.9 Millimeters of mercury (mmHg) | Standard Deviation 9 |
| Canagliflozin + Semaglutide Placebo | Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) | Systolic blood pressure | -5.8 Millimeters of mercury (mmHg) | Standard Deviation 13.5 |
Secondary
Change in Waist Circumference
Change from baseline (week 0) to week 52 in waist circumference was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Change in Waist Circumference | -4.2 Centimeter (cm) | Standard Deviation 6.2 |
| Canagliflozin + Semaglutide Placebo | Change in Waist Circumference | -3.0 Centimeter (cm) | Standard Deviation 5.4 |
Secondary
Eye Examination
Fundus photography or a dilated fundoscopy was performed by the investigator at baseline (week 0) and week 52. The results of the examination were interpreted for each eye (left/right) are categorised as normal, abnormal NCS or abnormal CS. Number of participants in each category at baseline and week 52 were presented. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Week 0, week 52
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Eye Examination | Left eye: Abnormal NCS (week 0) | 65 Participants |
| Semaglutide + Canagliflozin Placebo | Eye Examination | Left eye: Abnormal CS (week 0) | 5 Participants |
| Semaglutide + Canagliflozin Placebo | Eye Examination | Left eye: Normal (week 52) | 231 Participants |
| Semaglutide + Canagliflozin Placebo | Eye Examination | Left eye: Normal (week 0) | 322 Participants |
| Semaglutide + Canagliflozin Placebo | Eye Examination | Left eye: Abnormal NCS (week 52) | 30 Participants |
| Semaglutide + Canagliflozin Placebo | Eye Examination | Left eye: Abnormal CS (week 52) | 7 Participants |
| Semaglutide + Canagliflozin Placebo | Eye Examination | Right eye: Normal (week 0) | 321 Participants |
| Semaglutide + Canagliflozin Placebo | Eye Examination | Right eye: Abnormal NCS (week 0) | 66 Participants |
| Semaglutide + Canagliflozin Placebo | Eye Examination | Right eye: Abnormal CS (week 0) | 5 Participants |
| Semaglutide + Canagliflozin Placebo | Eye Examination | Right eye: Normal (week 52) | 225 Participants |
| Semaglutide + Canagliflozin Placebo | Eye Examination | Right eye: Abnormal NCS (week 52) | 35 Participants |
| Semaglutide + Canagliflozin Placebo | Eye Examination | Right eye: Abnormal CS (week 52) | 8 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Left eye: Abnormal CS (week 52) | 2 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Right eye: Abnormal CS (week 0) | 4 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Left eye: Abnormal CS (week 0) | 3 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Right eye: Normal (week 0) | 319 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Left eye: Normal (week 52) | 228 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Right eye: Abnormal CS (week 52) | 0 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Right eye: Abnormal NCS (week 52) | 44 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Left eye: Normal (week 0) | 319 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Left eye: Abnormal NCS (week 0) | 71 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Right eye: Abnormal NCS (week 0) | 70 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Left eye: Abnormal NCS (week 52) | 40 Participants |
| Canagliflozin + Semaglutide Placebo | Eye Examination | Right eye: Normal (week 52) | 226 Participants |
Secondary
Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no)
Percentage of participants who achieved HbA1c ≤ 6.5% (48 mmol/mol), AACE target (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no) | Yes | 62.1 Percentage of participants |
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no) | No | 37.9 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no) | Yes | 26.8 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no) | No | 73.2 Percentage of participants |
Secondary
Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no)
Percentage of participants who achieved HbA1c \< 7.0% (53 millimoles per mole \[mmol/mol\]), ADA target (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no) | No | 23.9 Percentage of participants |
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no) | Yes | 76.1 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no) | No | 49.2 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no) | Yes | 50.8 Percentage of participants |
Secondary
Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/no)
Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value \<3.1 mmol/L (56 milligrams per deciliter \[mg/dL\]) with symptoms consistent with hypoglycaemia. Percentage of participants who achieved HbA1c below 7.0% (53 mmol/mol) without severe or blood glucose confirmed symptomatic hypoglycaemia episodes and no weight gain (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/no) | No | 30.4 Percentage of participants |
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/no) | Yes | 69.6 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/no) | Yes | 45.0 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/no) | No | 55.0 Percentage of participants |
Secondary
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no)
Percentage of participants who achieved ≥1% reduction of baseline HbA1c and losing ≥10% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no) | No | 78.2 Percentage of participants |
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no) | Yes | 21.8 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no) | Yes | 6.1 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no) | No | 93.9 Percentage of participants |
Secondary
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no)
Percentage of participants who achieved ≥1% reduction of baseline HbA1c and losing ≥3% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no) | Yes | 57.3 Percentage of participants |
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no) | No | 42.7 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no) | Yes | 34.8 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no) | No | 65.2 Percentage of participants |
Secondary
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no)
Percentage of participants who achieved ≥1% reduction of baseline HbA1c and losing ≥5% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no) | Yes | 45.1 Percentage of participants |
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no) | No | 54.9 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no) | Yes | 25.9 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no) | No | 74.1 Percentage of participants |
Secondary
Participants Who Achieved HbA1c Reduction ≥1% (Yes/no)
Percentage of participants who achieved ≥1% reduction of baseline HbA1c (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c Reduction ≥1% (Yes/no) | Yes | 76.5 Percentage of participants |
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved HbA1c Reduction ≥1% (Yes/no) | No | 23.5 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c Reduction ≥1% (Yes/no) | Yes | 48.6 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved HbA1c Reduction ≥1% (Yes/no) | No | 51.4 Percentage of participants |
Secondary
Participants Who Achieved Weight Loss ≥10% (Yes/no)
Percentage of participants losing ≥10% of baseline body weight is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved Weight Loss ≥10% (Yes/no) | Yes | 23.2 Percentage of participants |
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved Weight Loss ≥10% (Yes/no) | No | 76.8 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved Weight Loss ≥10% (Yes/no) | No | 91.1 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved Weight Loss ≥10% (Yes/no) | Yes | 8.9 Percentage of participants |
Secondary
Participants Who Achieved Weight Loss ≥3% (Yes/no)
Percentage of participants losing ≥3% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved Weight Loss ≥3% (Yes/no) | Yes | 68.8 Percentage of participants |
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved Weight Loss ≥3% (Yes/no) | No | 31.2 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved Weight Loss ≥3% (Yes/no) | Yes | 64.9 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved Weight Loss ≥3% (Yes/no) | No | 35.1 Percentage of participants |
Secondary
Participants Who Achieved Weight Loss ≥5% (Yes/no)
Percentage of participants losing ≥5% of baseline body weight (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved Weight Loss ≥5% (Yes/no) | Yes | 52.7 Percentage of participants |
| Semaglutide + Canagliflozin Placebo | Participants Who Achieved Weight Loss ≥5% (Yes/no) | No | 47.3 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved Weight Loss ≥5% (Yes/no) | Yes | 47.0 Percentage of participants |
| Canagliflozin + Semaglutide Placebo | Participants Who Achieved Weight Loss ≥5% (Yes/no) | No | 53.0 Percentage of participants |
Secondary
Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
Number of participants with treatment emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes. Hypoglycaemic episodes defined as treatment-emergent if the onset of the episode occurs within the on-treatment observation period. Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Weeks 0-57
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide + Canagliflozin Placebo | Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes | 6 Participants |
| Canagliflozin + Semaglutide Placebo | Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes | 5 Participants |
Secondary
Percentage Change in Body Weight (%)
Change from baseline (week 0) to week 52 in body weight was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: Full analysis set comprised of all randomised participants. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Percentage Change in Body Weight (%) | -6.2 Percentage change | Standard Deviation 6.1 |
| Canagliflozin + Semaglutide Placebo | Percentage Change in Body Weight (%) | -4.7 Percentage change | Standard Deviation 4 |
Secondary
Percentage Change in Total Fat Mass (%)
Change from baseline (week 0) to week 52 in total fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Percentage Change in Total Fat Mass (%) | -1.55 Percentage change | Standard Deviation 2.76 |
| Canagliflozin + Semaglutide Placebo | Percentage Change in Total Fat Mass (%) | -1.21 Percentage change | Standard Deviation 2.64 |
Secondary
Percentage Change in Total Lean Mass (%)
Change from baseline (week 0) to week 52 in total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Percentage Change in Total Lean Mass (%) | 1.38 Percentage change | Standard Deviation 2.66 |
| Canagliflozin + Semaglutide Placebo | Percentage Change in Total Lean Mass (%) | 1.09 Percentage change | Standard Deviation 2.56 |
Secondary
Percentage Change in Visceral Fat Mass (%)
Change from baseline (week 0) to week 52 in visceral fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.
Time frame: Week 0, week 52
Population: DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. Number analyzed=participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide + Canagliflozin Placebo | Percentage Change in Visceral Fat Mass (%) | -0.81 Percentage change | Standard Deviation 7.3 |
| Canagliflozin + Semaglutide Placebo | Percentage Change in Visceral Fat Mass (%) | 0.16 Percentage change | Standard Deviation 4.36 |
Secondary
Total Number of Treatment Emergent Adverse Events (TEAEs)
A TEAE is defined as an adverse event with onset in the on-treatment observation period (which started at the date of first dose of trial product and included the period after initiation of rescue medication, if any and excluded the period after premature trial product discontinuation, if any. TEAEs assessed up to approximately 57 weeks is presented.
Time frame: Weeks 0-57
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide + Canagliflozin Placebo | Total Number of Treatment Emergent Adverse Events (TEAEs) | 1189 Adverse events |
| Canagliflozin + Semaglutide Placebo | Total Number of Treatment Emergent Adverse Events (TEAEs) | 1138 Adverse events |
Secondary
Total Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
Hypoglycaemic episodes defined as treatment-emergent if the onset of the episode occurs within the on-treatment observation period. Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment' observation period which started at the date of first dose of trial product and include the period after initiation of rescue medication, if any and excludes the period after premature trial product discontinuation, if any.
Time frame: Weeks 0-57
Population: Safety analysis set comprised of participants exposed to at least one dose of trial product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide + Canagliflozin Placebo | Total Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes | 25 Episodes |
| Canagliflozin + Semaglutide Placebo | Total Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes | 6 Episodes |