SUSTAIN 8: Efficacy and Safety of Semaglutide Versus Canagliflozin as add-on to Metformin in Subjects With Type 2 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03136484
• Collaborator: (none)
• Enrollment: 788
• Locations: 119
• Arms: 2
• Actual Duration (Months): 20.1
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: Semaglutide; Drug: Canagliflozin; Drug: Placebo (canagliflozin); Drug: Placebo (semaglutide)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 788 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Semaglutide Versus Canagliflozin as add-on to Metformin in Subjects With Type 2 Diabetes
• Actual Study Start Date: Mar 15, 2017
• Actual Primary Completion Date: Oct 16, 2018
• Actual Study Completion Date: Nov 16, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide + canagliflozin placebo	Drug: Semaglutide; 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.; Drug: Placebo (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.
Active Comparator: Canagliflozin + semaglutide placebo	Drug: Canagliflozin; 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.; Drug: Placebo (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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 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.

37. 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.

38. 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.

39. 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.

40. 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.

41. 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.

42. 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.

43. 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.

44. 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.

45. 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.

46. 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.

47. 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.

48. 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.

49. 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.

50. 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.

51. 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.

52. 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.

53. 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.

54. 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.

55. 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.

56. 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.

57. 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.

58. 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.

59. 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.

60. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Anaheim	California	United States	92801
2	Novo Nordisk Investigational Site	La Mesa	California	United States	91942
3	Novo Nordisk Investigational Site	Los Angeles	California	United States	90057
4	Novo Nordisk Investigational Site	Montclair	California	United States	91763
5	Novo Nordisk Investigational Site	San Diego	California	United States	92111
6	Novo Nordisk Investigational Site	Spring Valley	California	United States	91978
7	Novo Nordisk Investigational Site	Tustin	California	United States	92780
8	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598
9	Novo Nordisk Investigational Site	Fleming Island	Florida	United States	32003
10	Novo Nordisk Investigational Site	Hallandale Beach	Florida	United States	33009
11	Novo Nordisk Investigational Site	Hialeah	Florida	United States	33012
12	Novo Nordisk Investigational Site	Miami	Florida	United States	33135
13	Novo Nordisk Investigational Site	Miami	Florida	United States	33155
14	Novo Nordisk Investigational Site	Miami	Florida	United States	33174
15	Novo Nordisk Investigational Site	Miami	Florida	United States	33175
16	Novo Nordisk Investigational Site	Miami	Florida	United States	33186
17	Novo Nordisk Investigational Site	Spring Hill	Florida	United States	34609
18	Novo Nordisk Investigational Site	Conyers	Georgia	United States	30094-5965
19	Novo Nordisk Investigational Site	Marietta	Georgia	United States	30060
20	Novo Nordisk Investigational Site	Meridian	Idaho	United States	83646
21	Novo Nordisk Investigational Site	Council Bluffs	Iowa	United States	51501
22	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
23	Novo Nordisk Investigational Site	Lake Charles	Louisiana	United States	70601
24	Novo Nordisk Investigational Site	Metairie	Louisiana	United States	70002
25	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21239
26	Novo Nordisk Investigational Site	Hyattsville	Maryland	United States	20782
27	Novo Nordisk Investigational Site	Detroit	Michigan	United States	48202
28	Novo Nordisk Investigational Site	Flint	Michigan	United States	48504
29	Novo Nordisk Investigational Site	Flint	Michigan	United States	48532
30	Novo Nordisk Investigational Site	Sterling Heights	Michigan	United States	48310-3503
31	Novo Nordisk Investigational Site	Troy	Michigan	United States	48098
32	Novo Nordisk Investigational Site	Trenton	New Jersey	United States	08611
33	Novo Nordisk Investigational Site	Brooklyn	New York	United States	11229
34	Novo Nordisk Investigational Site	New Windsor	New York	United States	12553
35	Novo Nordisk Investigational Site	Greensboro	North Carolina	United States	27408
36	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45212
37	Novo Nordisk Investigational Site	Maumee	Ohio	United States	43537
38	Novo Nordisk Investigational Site	Toledo	Ohio	United States	43614
39	Novo Nordisk Investigational Site	Toledo	Ohio	United States	43623
40	Novo Nordisk Investigational Site	Corvallis	Oregon	United States	97330-3737
41	Novo Nordisk Investigational Site	Anderson	South Carolina	United States	29621
42	Novo Nordisk Investigational Site	Amarillo	Texas	United States	79106
43	Novo Nordisk Investigational Site	Corpus Christi	Texas	United States	78404
44	Novo Nordisk Investigational Site	Corpus Christi	Texas	United States	78413
45	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
46	Novo Nordisk Investigational Site	Dallas	Texas	United States	75251
47	Novo Nordisk Investigational Site	Dallas	Texas	United States	75390-9302
48	Novo Nordisk Investigational Site	Houston	Texas	United States	77058
49	Novo Nordisk Investigational Site	Houston	Texas	United States	77074
50	Novo Nordisk Investigational Site	Houston	Texas	United States	77081
51	Novo Nordisk Investigational Site	Katy	Texas	United States	77450
52	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78230
53	Novo Nordisk Investigational Site	Splendora	Texas	United States	77372
54	Novo Nordisk Investigational Site	Saint George	Utah	United States	84790
55	Novo Nordisk Investigational Site	Herndon	Virginia	United States	20171
56	Novo Nordisk Investigational Site	Olympia	Washington	United States	98502
57	Novo Nordisk Investigational Site	Wenatchee	Washington	United States	98801-2028
58	Novo Nordisk Investigational Site	Buenos Aires		Argentina	C1250AAN
59	Novo Nordisk Investigational Site	Caba		Argentina	C1093AAS
60	Novo Nordisk Investigational Site	Caba		Argentina	C1430CKE
61	Novo Nordisk Investigational Site	Rosario		Argentina	S2000CUD
62	Novo Nordisk Investigational Site	Salta		Argentina	4400
63	Novo Nordisk Investigational Site	Porto Alegre		Brazil	90035-170
64	Novo Nordisk Investigational Site	Rio de Janeiro		Brazil	22271-100
65	Novo Nordisk Investigational Site	Surrey	British Columbia	Canada	V3S 2N6
66	Novo Nordisk Investigational Site	Brampton	Ontario	Canada	L6T 0G1
67	Novo Nordisk Investigational Site	Burlington	Ontario	Canada	L7M 4Y1
68	Novo Nordisk Investigational Site	London	Ontario	Canada	N5W 6A2
69	Novo Nordisk Investigational Site	Sarnia	Ontario	Canada	N7T 4X3
70	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M9V 4B4
71	Novo Nordisk Investigational Site	Pointe Claire	Quebec	Canada	H9R 4S3
72	Novo Nordisk Investigational Site	Pointe-Claire	Quebec	Canada	H9R 3J1
73	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh	India	500034
74	Novo Nordisk Investigational Site	Rohtak	Haryana	India	124001
75	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560054
76	Novo Nordisk Investigational Site	Kochi	Kerala	India	682041
77	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400008
78	Novo Nordisk Investigational Site	Nagpur	Maharashtra	India	440008
79	Novo Nordisk Investigational Site	Jaipur	Rajasthan	India	302006
80	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600 013
81	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600001
82	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700020
83	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700054
84	Novo Nordisk Investigational Site	Dublin		Ireland	DUBLIN 15
85	Novo Nordisk Investigational Site	Dublin		Ireland	DUBLIN 4
86	Novo Nordisk Investigational Site	Dublin		Ireland	DUBLIN 7
87	Novo Nordisk Investigational Site	Galway		Ireland	H91 YR71
88	Novo Nordisk Investigational Site	Mallow		Ireland	P51Y8EC
89	Novo Nordisk Investigational Site	Milano		Italy	20100
90	Novo Nordisk Investigational Site	Achrafieh		Lebanon
91	Novo Nordisk Investigational Site	Hazmieh		Lebanon
92	Novo Nordisk Investigational Site	Lebanon - Beirut		Lebanon	9611
93	Novo Nordisk Investigational Site	Mansourieh		Lebanon
94	Novo Nordisk Investigational Site	Zgharta		Lebanon	9616
95	Novo Nordisk Investigational Site	Alor Gajah		Malaysia	78300
96	Novo Nordisk Investigational Site	Ipoh		Malaysia	30450
97	Novo Nordisk Investigational Site	Melaka		Malaysia	75400
98	Novo Nordisk Investigational Site	Penang		Malaysia	10450
99	Novo Nordisk Investigational Site	Sandakan		Malaysia	90000
100	Novo Nordisk Investigational Site	Seremban		Malaysia	70300
101	Novo Nordisk Investigational Site	Cuernavaca	Morelos	Mexico	62250
102	Novo Nordisk Investigational Site	Mexico City	México, D.F.	Mexico	02230
103	Novo Nordisk Investigational Site	Monterrey	Nuevo León	Mexico	64620
104	Novo Nordisk Investigational Site	Eksjö		Sweden	575 35
105	Novo Nordisk Investigational Site	Kristianstad		Sweden	291 85
106	Novo Nordisk Investigational Site	Lund		Sweden	221 85
107	Novo Nordisk Investigational Site	Malmö		Sweden	205 02
108	Novo Nordisk Investigational Site	Örebro		Sweden	701 85
109	Novo Nordisk Investigational Site	Basingstoke		United Kingdom	RG24 9GT
110	Novo Nordisk Investigational Site	Bradford-on-Avon		United Kingdom	BA15 1DQ
111	Novo Nordisk Investigational Site	Dundee		United Kingdom	DD1 9SY
112	Novo Nordisk Investigational Site	Haxey		United Kingdom	DN9 2HY
113	Novo Nordisk Investigational Site	Nottingham		United Kingdom	NG7 2UH
114	Novo Nordisk Investigational Site	Plymouth		United Kingdom	PL8 8DQ
115	Novo Nordisk Investigational Site	Soham		United Kingdom	CB7 5JD
116	Novo Nordisk Investigational Site	Southampton		United Kingdom	SO30 3JB
117	Novo Nordisk Investigational Site	Stevenage		United Kingdom	SG1 4AB
118	Novo Nordisk Investigational Site	Torquay		United Kingdom	TQ2 7AA
119	Novo Nordisk Investigational Site	Wellingborough		United Kingdom	NN8 4RW

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 3, 2019
• Statistical Analysis Plan - Jun 3, 2019

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03136484
• Other Study ID Numbers: NN9535-4270; 2016-000989-35; U1111-1180-3651
• First Posted: May 2, 2017
• Last Update Posted: Jan 21, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Canagliflozin

Study Results

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 Detail	Study design: Body composition (sub-study) was measured using dual x-ray absorptiometry (DXA) scans in a planned subset of randomised participants.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	Participants received subcutaneous (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.	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.
Period Title: Overall Study
STARTED	394	394
Exposed	392	394
COMPLETED	367	372
NOT COMPLETED	27	22

Baseline Characteristics

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	394	394	788
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	55.7 (11.1)	57.5 (10.7)	56.6 (10.9)
Sex: Female, Male (Count of Participants)
Female	171 43.4%	193 49%	364 46.2%
Male	223 56.6%	201 51%	424 53.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	156 39.6%	137 34.8%	293 37.2%
Not Hispanic or Latino	238 60.4%	257 65.2%	495 62.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
Race : American Indian or Alaska native	1 0.3%	3 0.8%	4 0.5%
Race : Asian	62 15.7%	63 16%	125 15.9%
Race : Black or African American	28 7.1%	30 7.6%	58 7.4%
Race : Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Race : White	297 75.4%	290 73.6%	587 74.5%
Race : Other	6 1.5%	7 1.8%	13 1.6%
Race : Not Applicable	0 0%	1 0.3%	1 0.1%
HbA1c (Percentage (%) of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage (%) of HbA1c]	8.3 (1.0)	8.2 (1.0)	8.3 (1.0)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
On-treatment without rescue medication	-1.7 (1.1)	-1.0 (1.0)
In-trial	-1.5 (1.3)	-1.0 (1.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide + Canagliflozin Placebo, Canagliflozin + Semaglutide Placebo
	Comments	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.
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority p-value was calculated as two times the one-sided p-value from a t-distributed test statistic comparing the treatment contrast with 0.3 rather than zero as in a superiority test.
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -0.65 to -0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Semaglutide + canagliflozin placebo vs Canagliflozin + semaglutide placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide + Canagliflozin Placebo, Canagliflozin + Semaglutide Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -0.65 to -0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Semaglutide + canagliflozin placebo vs Canagliflozin + semaglutide placebo

2. Secondary Outcome

Title	Change in Body Weight (kg)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Mean (Standard Deviation) [Kilogram (kg)]	-5.7 (5.4)	-4.3 (4.0)

3. Secondary Outcome

Title	Change in Total Fat Mass (kg)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	88	90
Mean (Standard Deviation) [kg]	-3.72 (4.50)	-2.63 (3.30)

4. Secondary Outcome

Title	Change in FPG (Fasting Plasma Glucose)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Mean (Standard Deviation) [Millimoles per liter (mmol/L)]	-2.54 (2.77)	-2.00 (2.53)

5. Secondary Outcome

Title	Change in SMPG (Self-measured Plasma Glucose)- Mean 7-point Profile
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Mean (Standard Deviation) [mmol/L]	-2.8 (2.3)	-1.9 (2.7)

6. Secondary Outcome

Title	Change in SMPG- Mean Postprandial Increment Over All Meals
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Mean (Standard Deviation) [mmol/L]	-0.6 (2.1)	-0.6 (2.0)

7. Secondary Outcome

Title	Change in Fasting Total Cholesterol
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of total cholesterol]	0.96 (19.3)	1.03 (18.2)

8. Secondary Outcome

Title	Change in Fasting LDL-cholesterol
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of LDL-cholesterol]	0.96 (32.2)	1.05 (29.0)

9. Secondary Outcome

Title	Change in Fasting HDL-cholesterol
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of HDL-cholesterol]	1.04 (13.1)	1.08 (13.6)

10. Secondary Outcome

Title	Change in Fasting Triglycerides
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of triglycerides]	0.86 (40.6)	0.92 (38.2)

11. Secondary Outcome

Title	Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Systolic blood pressure	-3.7 (14.0)	-5.8 (13.5)
Diastolic blood pressure	-1.2 (9.8)	-2.9 (9.0)

12. Secondary Outcome

Title	Percentage Change in Body Weight (%)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Mean (Standard Deviation) [Percentage change]	-6.2 (6.1)	-4.7 (4.0)

13. Secondary Outcome

Title	Change in Body Mass Index (BMI)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Mean (Standard Deviation) [Kilogram per square meter (kg/m^2)]	-2.0 (2.0)	-1.5 (1.4)

14. Secondary Outcome

Title	Change in Waist Circumference
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Mean (Standard Deviation) [Centimeter (cm)]	-4.2 (6.2)	-3.0 (5.4)

15. Secondary Outcome

Title	Percentage Change in Total Fat Mass (%)
Description	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

Outcome Measure Data

Analysis Population Description

DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	88	90
Mean (Standard Deviation) [Percentage change]	-1.55 (2.76)	-1.21 (2.64)

16. Secondary Outcome

Title	Change in Total Lean Mass (kg)
Description	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

Outcome Measure Data

Analysis Population Description

DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	88	90
Mean (Standard Deviation) [kg]	-2.06 (2.15)	-1.53 (2.21)

17. Secondary Outcome

Title	Percentage Change in Total Lean Mass (%)
Description	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

Outcome Measure Data

Analysis Population Description

DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	88	90
Mean (Standard Deviation) [Percentage change]	1.38 (2.66)	1.09 (2.56)

18. Secondary Outcome

Title	Change in Visceral Fat Mass (kg)
Description	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

Outcome Measure Data

Analysis Population Description

DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	88	90
Mean (Standard Deviation) [kg]	-0.20 (0.40)	-0.13 (0.32)

19. Secondary Outcome

Title	Percentage Change in Visceral Fat Mass (%)
Description	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

Outcome Measure Data

Analysis Population Description

DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	88	90
Mean (Standard Deviation) [Percentage change]	-0.81 (7.30)	0.16 (4.36)

20. Secondary Outcome

Title	Change in Ratio Between Total Fat Mass and Total Lean Mass
Description	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

Outcome Measure Data

Analysis Population Description

DXA analysis set comprised of all randomised participants who are included in the body composition sub-study. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	88	90
Mean (Standard Deviation) [total fat mass/total lean mass ratio]	-0.04 (0.08)	-0.03 (0.07)

21. Secondary Outcome

Title	Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	293	313
Yes	76.1 19.3%	50.8 12.9%
No	23.9 6.1%	49.2 12.5%

22. Secondary Outcome

Title	Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	293	313
Yes	62.1 15.8%	26.8 6.8%
No	37.9 9.6%	73.2 18.6%

23. Secondary Outcome

Title	Participants Who Achieved HbA1c Reduction ≥1% (Yes/no)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	293	313
Yes	76.5 19.4%	48.6 12.3%
No	23.5 6%	51.4 13%

24. Secondary Outcome

Title	Participants Who Achieved Weight Loss ≥3% (Yes/no)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	298	313
Yes	68.8 17.5%	64.9 16.5%
No	31.2 7.9%	35.1 8.9%

25. Secondary Outcome

Title	Participants Who Achieved Weight Loss ≥5% (Yes/no)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	298	313
Yes	52.7 13.4%	47.0 11.9%
No	47.3 12%	53.0 13.5%

26. Secondary Outcome

Title	Participants Who Achieved Weight Loss ≥10% (Yes/no)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	298	313
Yes	23.2 5.9%	8.9 2.3%
No	76.8 19.5%	91.1 23.1%

27. Secondary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	293	313
Yes	69.6 17.7%	45.0 11.4%
No	30.4 7.7%	55.0 14%

28. Secondary Outcome

Title	Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	293	313
Yes	57.3 14.5%	34.8 8.8%
No	42.7 10.8%	65.2 16.5%

29. Secondary Outcome

Title	Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	293	313
Yes	45.1 11.4%	25.9 6.6%
No	54.9 13.9%	74.1 18.8%

30. Secondary Outcome

Title	Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	293	313
Yes	21.8 5.5%	6.1 1.5%
No	78.2 19.8%	93.9 23.8%

31. Secondary Outcome

Title	Total Number of Treatment Emergent Adverse Events (TEAEs)
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Number [Adverse events]	1189	1138

32. Secondary Outcome

Title	Change in Haematological Parameter- Haemoglobin
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of haemoglobin]	0.99 (8.0)	1.05 (8.5)

33. Secondary Outcome

Title	Change in Haematological Parameter- Haematocrit
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of haematocrit]	0.99 (6.8)	1.04 (6.9)

34. Secondary Outcome

Title	Change in Haematological Parameter- Erythrocytes
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of erythrocytes]	0.99 (5.7)	1.04 (6.0)

35. Secondary Outcome

Title	Change in Haematological Parameter- Leukocytes
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of leukocytes]	0.97 (20.3)	0.98 (17.5)

36. Secondary Outcome

Title	Change in Haematological Parameter- Thrombocytes
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of thrombocytes]	1.04 (14.4)	1.00 (15.4)

37. Secondary Outcome

Title	Change in Biochemistry Parameter- Amylase
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of amylase]	1.16 (26.5)	1.09 (24.4)

38. Secondary Outcome

Title	Change in Biochemistry Parameter- Lipase
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of lipase]	1.25 (54.5)	1.01 (51.5)

39. Secondary Outcome

Title	Change in Biochemistry Parameter- ALT
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of ALT]	0.79 (49.5)	0.79 (45.3)

40. Secondary Outcome

Title	Change in Biochemistry Parameter- AST
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of AST]	0.89 (37.5)	0.86 (37.4)

41. Secondary Outcome

Title	Change in Biochemistry Parameter- ALP
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of ALP]	0.96 (19.6)	0.95 (16.8)

42. Secondary Outcome

Title	Change in Biochemistry Parameter- Total Bilirubin
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of total bilirubin]	1.06 (32.1)	1.13 (33.9)

43. Secondary Outcome

Title	Change in Biochemistry Parameter- Creatinine
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of creatinine]	1.03 (11.0)	1.04 (11.9)

44. Secondary Outcome

Title	Change in Biochemistry Parameter- eGFR
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of eGFR]	0.98 (8.4)	0.96 (9.7)

45. Secondary Outcome

Title	Change in Biochemistry Parameter- Albumin
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of albumin]	0.99 (5.4)	1.00 (5.2)

46. Secondary Outcome

Title	Change in Biochemistry Parameter- Calcium
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of calcium]	1.01 (4.5)	1.02 (4.1)

47. Secondary Outcome

Title	Change in Biochemistry Parameter- Potassium
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of potassium]	1.00 (9.3)	1.00 (8.6)

48. Secondary Outcome

Title	Change in Biochemistry Parameter- Sodium
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of sodium]	1.00 (1.6)	1.00 (1.5)

49. Secondary Outcome

Title	Change in Calcitonin
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Geometric Mean (Geometric Coefficient of Variation) [Ratio of calcitonin]	1.08 (43.8)	1.04 (35.6)

50. Secondary Outcome

Title	Change in Pulse
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Mean (Standard Deviation) [Beats per minute (beats/min)]	2.7 (9.5)	-0.6 (8.6)

51. Secondary Outcome

Title	Change in ECG
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Normal (week 0)	263 66.8%	277 70.3%
Abnormal NCS (week 0)	126 32%	117 29.7%
Abnormal CS (week 0)	3 0.8%	0 0%
Normal (week 52)	222 56.3%	242 61.4%
Abnormal NCS (week 52)	109 27.7%	95 24.1%
Abnormal CS (week 52)	0 0%	3 0.8%

52. Secondary Outcome

Title	Change in Physical Examination
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
General Appearance (week -2) Normal	345 87.6%	335 85%
General Appearance (week -2) Abnormal NCS	46 11.7%	56 14.2%
General Appearance (week -2) Abnormal CS	1 0.3%	3 0.8%
General Appearance (week 52) Normal	294 74.6%	304 77.2%
General Appearance (week 52) Abnormal NCS	30 7.6%	33 8.4%
General Appearance (week 52) Abnormal CS	2 0.5%	2 0.5%
Nervous System (week -2) Normal	360 91.4%	370 93.9%
Nervous System (week -2) Abnormal NCS	26 6.6%	21 5.3%
Nervous System (week -2) Abnormal CS	5 1.3%	3 0.8%
Nervous System (week 52) Normal	303 76.9%	325 82.5%
Nervous System (week 52) Abnormal NCS	21 5.3%	12 3%
Nervous System (week 52) Abnormal CS	2 0.5%	2 0.5%
Cardiovascular System (week-2) Normal	376 95.4%	386 98%
Cardiovascular System (week -2) Abnormal NCS	15 3.8%	8 2%
Cardiovascular System (week -2) Abnormal CS	1 0.3%	0 0%
Cardiovascular System (week52) Normal	318 80.7%	333 84.5%
Cardiovascular System (week 52) Abnormal NCS	7 1.8%	6 1.5%
Cardiovascular System (week 52) Abnormal CS	1 0.3%	0 0%
Gastrointestinal System (week -2) Normal	369 93.7%	377 95.7%
Gastrointestinal System (week -2) Abnormal NCS	22 5.6%	16 4.1%
Gastrointestinal System (week -2) Abnormal CS	1 0.3%	1 0.3%
Gastrointestinal System (week 52) Normal	319 81%	331 84%
Gastrointestinal System (week 52) Abnormal NCS	7 1.8%	8 2%
Gastrointestinal System (week 52) Abnormal CS	0 0%	0 0%
Skin (week -2) Normal	330 83.8%	323 82%
Skin (week -2) Abnormal NCS	62 15.7%	69 17.5%
Skin (week -2) Abnormal CS	0 0%	2 0.5%
Skin (week 52) Normal	286 72.6%	298 75.6%
Skin (week 52) Abnormal NCS	39 9.9%	40 10.2%
Skin (week 52) Abnormal CS	1 0.3%	1 0.3%
Respiratory System (week -2) Normal	383 97.2%	391 99.2%
Respiratory System (week -2) Abnormal NCS	7 1.8%	3 0.8%
Respiratory System (week -2) Abnormal CS	2 0.5%	0 0%
Respiratory System (week 52) Normal	321 81.5%	336 85.3%
Respiratory System (week 52) Abnormal NCS	4 1%	3 0.8%
Respiratory System (week 52) Abnormal CS	1 0.3%	0 0%
Lymph Node Palpation (week -2) Normal	390 99%	392 99.5%
Lymph Node Palpation (week -2) Abnormal NCS	1 0.3%	2 0.5%
Lymph Node Palpation (week -2) Abnormal CS	0 0%	0 0%
Lymph Node Palpation (week 52) Normal	325 82.5%	337 85.5%
Lymph Node Palpation (week 52) Abnormal NCS	0 0%	0 0%
Lymph Node Palpation (week 52) Abnormal CS	0 0%	0 0%
Thyroid Gland (week -2) Normal	390 99%	390 99%
Thyroid Gland (week -2) Abnormal NCS	2 0.5%	4 1%
Thyroid Gland (week -2) Abnormal CS	0 0%	0 0%
Thyroid Gland (week 52) Normal	326 82.7%	337 85.5%
Thyroid Gland (week 52) Abnormal NCS	0 0%	1 0.3%
Thyroid Gland (week 52) Abnormal CS	0 0%	0 0%
Left foot (week -2) Normal	343 87.1%	345 87.6%
Left foot (week -2) Abnormal NCS	47 11.9%	44 11.2%
Left foot (week -2) Abnormal CS	2 0.5%	5 1.3%
Left foot (week 52) Normal	293 74.4%	303 76.9%
Left foot (week 52) Abnormal NCS	32 8.1%	34 8.6%
Left foot (week 52) Abnormal CS	1 0.3%	2 0.5%
Right foot (week -2) Normal	344 87.3%	348 88.3%
Right foot (week -2) Abnormal NCS	45 11.4%	42 10.7%
Right foot (week -2) Abnormal CS	3 0.8%	4 1%
Right foot (week 52) Normal	289 73.4%	304 77.2%
Right foot (week 52) Abnormal NCS	34 8.6%	32 8.1%
Right foot (week 52) Abnormal CS	3 0.8%	3 0.8%
Left leg (week -2) Normal	348 88.3%	358 90.9%
Left leg (week -2) Abnormal NCS	40 10.2%	30 7.6%
Left leg (week -2) Abnormal CS	4 1%	6 1.5%
Left leg (week 52) Normal	300 76.1%	314 79.7%
Left leg (week 52) Abnormal NCS	22 5.6%	22 5.6%
Left leg (week 52) Abnormal CS	4 1%	3 0.8%
Right leg (week -2) Normal	350 88.8%	357 90.6%
Right leg (week -2) Abnormal NCS	37 9.4%	30 7.6%
Right leg (week -2) Abnormal CS	5 1.3%	7 1.8%
Right leg (week 52) Normal	301 76.4%	315 79.9%
Right leg (week 52) Abnormal NCS	19 4.8%	21 5.3%
Right leg (week 52) Abnormal CS	6 1.5%	3 0.8%

53. Secondary Outcome

Title	Eye Examination
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Left eye: Normal (week 0)	322 81.7%	319 81%
Left eye: Abnormal NCS (week 0)	65 16.5%	71 18%
Left eye: Abnormal CS (week 0)	5 1.3%	3 0.8%
Left eye: Normal (week 52)	231 58.6%	228 57.9%
Left eye: Abnormal NCS (week 52)	30 7.6%	40 10.2%
Left eye: Abnormal CS (week 52)	7 1.8%	2 0.5%
Right eye: Normal (week 0)	321 81.5%	319 81%
Right eye: Abnormal NCS (week 0)	66 16.8%	70 17.8%
Right eye: Abnormal CS (week 0)	5 1.3%	4 1%
Right eye: Normal (week 52)	225 57.1%	226 57.4%
Right eye: Abnormal NCS (week 52)	35 8.9%	44 11.2%
Right eye: Abnormal CS (week 52)	8 2%	0 0%

54. Secondary Outcome

Title	Total Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Number [Episodes]	25	6

55. Secondary Outcome

Title	Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
Description	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

Outcome Measure Data

Analysis Population Description

Safety analysis set comprised of participants exposed to at least one dose of trial product.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	392	394
Number [Participants]	6 1.5%	5 1.3%

56. Secondary Outcome

Title	Change in Short Form 36 Health Survey (SF-36): Sub-domains
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Physical Functioning	1.9 (7.1)	2.7 (6.7)
Role-physical	1.8 (7.3)	2.0 (7.1)
Bodily pain	2.5 (8.9)	1.5 (8.7)
General health	3.7 (7.7)	3.5 (8.5)
Social functioning	1.1 (8.6)	1.1 (8.0)
Role-emotional	0.8 (9.2)	1.2 (8.6)
Vitality	3.0 (8.2)	2.0 (8.2)
Mental health	1.5 (8.3)	0.6 (8.1)

57. Secondary Outcome

Title	Change in SF-36: Physical Component Summary (PCS)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Mean (Standard Deviation) [Score on a scale]	2.7 (6.7)	2.9 (6.2)

58. Secondary Outcome

Title	Change in SF-36: Mental Component Summary (MCS)
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Mean (Standard Deviation) [Score on a scale]	1.1 (8.8)	0.5 (8.0)

59. Secondary Outcome

Title	Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
1) Satisfaction with treatment	1.4 (1.6)	1.0 (1.6)
2) Feeling of unacceptably high blood sugars	-2.0 (2.2)	-1.8 (2.2)
3) Feeling of unacceptably low blood sugars	0.1 (1.9)	0.1 (1.6)
4) Convenience of treatment	0.8 (1.8)	0.7 (1.8)
5) Flexibility of current treatment	0.8 (1.7)	0.7 (1.7)
6) Satisfaction with understanding of diabetes	0.8 (1.5)	0.6 (1.3)
7) Recommending treatment to others	0.9 (1.5)	0.9 (1.5)
8) Satisfaction to continue with present treatment	1.1 (1.8)	0.8 (1.8)
Total treatment satisfaction score	5.8 (7.0)	4.8 (7.2)

60. Secondary Outcome

Title	Change in Control of Eating Questionnaire (CoEQ): Domains
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
Craving control	1.0 (2.1)	1.0 (2.5)
Craving for sweet	-0.6 (2.2)	-0.6 (2.1)
Craving for savoury	-1.1 (2.0)	-0.9 (2.0)
Positive mood	0.7 (1.7)	0.4 (1.6)

61. Secondary Outcome

Title	Change in CoEQ: Individual Items
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set comprised of all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Semaglutide + Canagliflozin Placebo	Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.	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.
Measure Participants	394	394
How hungry have you felt	-1.2 (2.6)	-0.8 (2.6)
How full have you felt	0.2 (2.7)	0.0 (2.7)
How often have you had cravings (last 7 days)	-0.9 (2.9)	-1.1 (3.0)
How strong have any cravings been	-0.9 (2.9)	-1.1 (3.0)
Difficulty to resist cravings	-0.9 (2.9)	-0.8 (3.2)
Ate in response to cravings	-0.9 (2.7)	-0.7 (3.2)
Difficulty to control eating	-1.5 (2.8)	-1.2 (3.0)
Desire to eat savory food	-1.4 (2.6)	-1.0 (2.8)
Craving for dairy foods	-0.8 (2.9)	-0.6 (3.1)
Craving for starchy foods	-1.4 (2.7)	-1.1 (3.0)
Craving for savory foods	-0.9 (2.9)	-0.9 (2.9)
Desire to eat sweet food	-0.9 (3.1)	-1.0 (2.9)
Craving for chocolate	-0.3 (3.1)	-0.4 (2.9)
Craving for other sweets	-0.6 (2.8)	-0.6 (2.8)
Craving for fruit or fruit juice	-0.6 (3.0)	-0.6 (3.2)
Felt happy	0.8 (2.5)	0.4 (2.3)
Felt anxious	-0.9 (3.1)	-0.6 (2.7)
Felt alert	0.2 (2.4)	0.0 (2.4)
Felt contented	0.8 (2.4)	0.5 (2.2)

Adverse Events

Time Frame	From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks.
Adverse Event Reporting Description	Evaluation of safety was based on SAS which comprised of all randomised participants who received at least one dose of trial product. AEs with onset during the on-treatment observation period (the period when participants were exposed to trial product) were considered treatment-emergent.
Arm/Group Title	Semaglutide + Canagliflozin Placebo		Canagliflozin + Semaglutide Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Semaglutide + Canagliflozin Placebo		Canagliflozin + Semaglutide Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/392 (0.3%)		0/394 (0%)
Serious Adverse Events
	Semaglutide + Canagliflozin Placebo		Canagliflozin + Semaglutide Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/392 (4.6%)		21/394 (5.3%)
Blood and lymphatic system disorders
Splenomegaly	0/392 (0%)	0	1/394 (0.3%)	1
Cardiac disorders
Angina unstable	0/392 (0%)	0	1/394 (0.3%)	1
Coronary artery disease	0/392 (0%)	0	1/394 (0.3%)	1
Coronary artery stenosis	0/392 (0%)	0	1/394 (0.3%)	1
Myocardial ischaemia	1/392 (0.3%)	1	0/394 (0%)	0
Ear and labyrinth disorders
Vertigo	0/392 (0%)	0	1/394 (0.3%)	1
Eye disorders
Cataract	1/392 (0.3%)	1	0/394 (0%)	0
Retinal infarction	1/392 (0.3%)	1	0/394 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	1/392 (0.3%)	1	0/394 (0%)	0
Ascites	0/392 (0%)	0	1/394 (0.3%)	1
Diarrhoea	1/392 (0.3%)	1	0/394 (0%)	0
Gastritis	0/392 (0%)	0	1/394 (0.3%)	1
Haemorrhoids thrombosed	0/392 (0%)	0	1/394 (0.3%)	1
Small intestinal obstruction	0/392 (0%)	0	1/394 (0.3%)	1
General disorders
Chest pain	0/392 (0%)	0	1/394 (0.3%)	1
Non-cardiac chest pain	1/392 (0.3%)	2	1/394 (0.3%)	1
Pyrexia	0/392 (0%)	0	2/394 (0.5%)	2
Hepatobiliary disorders
Cholecystitis chronic	0/392 (0%)	0	1/394 (0.3%)	1
Cholelithiasis	0/392 (0%)	0	3/394 (0.8%)	3
Hepatic cirrhosis	0/392 (0%)	0	1/394 (0.3%)	1
Infections and infestations
Cellulitis gangrenous	0/392 (0%)	0	1/394 (0.3%)	1
Cellulitis staphylococcal	0/392 (0%)	0	1/394 (0.3%)	1
Lower respiratory tract infection	0/392 (0%)	0	1/394 (0.3%)	1
Perirectal abscess	0/392 (0%)	0	1/394 (0.3%)	1
Pneumonia	1/392 (0.3%)	1	1/394 (0.3%)	1
Respiratory tract infection viral	0/392 (0%)	0	1/394 (0.3%)	1
Urinary tract infection	3/392 (0.8%)	3	0/394 (0%)	0
Urosepsis	1/392 (0.3%)	1	0/394 (0%)	0
Vulval abscess	0/392 (0%)	0	1/394 (0.3%)	1
Injury, poisoning and procedural complications
Airway complication of anaesthesia	1/392 (0.3%)	1	0/394 (0%)	0
Ankle fracture	0/392 (0%)	0	1/394 (0.3%)	1
Femur fracture	0/392 (0%)	0	1/394 (0.3%)	1
Patella fracture	1/392 (0.3%)	1	0/394 (0%)	0
Post procedural haematuria	1/392 (0.3%)	1	0/394 (0%)	0
Prescribed overdose	0/392 (0%)	0	1/394 (0.3%)	1
Road traffic accident	1/392 (0.3%)	1	0/394 (0%)	0
Investigations
Glomerular filtration rate decreased	1/392 (0.3%)	1	0/394 (0%)	0
Transaminases increased	0/392 (0%)	0	1/394 (0.3%)	1
Metabolism and nutrition disorders
Hypokalaemia	1/392 (0.3%)	1	0/394 (0%)	0
Hypomagnesaemia	1/392 (0.3%)	1	0/394 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer metastatic	0/392 (0%)	0	1/394 (0.3%)	1
Nervous system disorders
Aphasia	1/392 (0.3%)	1	0/394 (0%)	0
Basal ganglia haemorrhage	0/392 (0%)	0	1/394 (0.3%)	1
Ischaemic stroke	1/392 (0.3%)	1	0/394 (0%)	0
Transient ischaemic attack	0/392 (0%)	0	1/394 (0.3%)	1
Psychiatric disorders
Bipolar disorder	0/392 (0%)	0	1/394 (0.3%)	1
Confusional state	1/392 (0.3%)	1	0/394 (0%)	0
Renal and urinary disorders
Hydronephrosis	1/392 (0.3%)	1	0/394 (0%)	0
Nephrolithiasis	2/392 (0.5%)	2	0/394 (0%)	0
Ureterolithiasis	1/392 (0.3%)	1	0/394 (0%)	0
Reproductive system and breast disorders
Bartholin's cyst	0/392 (0%)	0	1/394 (0.3%)	1
Prostatism	0/392 (0%)	0	1/394 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/392 (0.3%)	1	0/394 (0%)	0
Pulmonary embolism	1/392 (0.3%)	1	0/394 (0%)	0
Vascular disorders
Arteriosclerosis	1/392 (0.3%)	1	0/394 (0%)	0
Deep vein thrombosis	1/392 (0.3%)	1	0/394 (0%)	0
Other (Not Including Serious) Adverse Events
	Semaglutide + Canagliflozin Placebo		Canagliflozin + Semaglutide Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	185/392 (47.2%)		120/394 (30.5%)
Gastrointestinal disorders
Constipation	20/392 (5.1%)	20	23/394 (5.8%)	23
Diarrhoea	59/392 (15.1%)	94	37/394 (9.4%)	58
Dyspepsia	22/392 (5.6%)	23	8/394 (2%)	8
Nausea	89/392 (22.7%)	127	26/394 (6.6%)	30
Vomiting	50/392 (12.8%)	77	9/394 (2.3%)	9
Infections and infestations
Nasopharyngitis	23/392 (5.9%)	25	26/394 (6.6%)	34
Metabolism and nutrition disorders
Decreased appetite	26/392 (6.6%)	26	6/394 (1.5%)	6
Musculoskeletal and connective tissue disorders
Back pain	11/392 (2.8%)	11	21/394 (5.3%)	21
Nervous system disorders
Headache	26/392 (6.6%)	48	27/394 (6.9%)	47

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.