Trial Outcomes & Findings for Efficacy and Safety of Semaglutide Versus Canagliflozin as add-on to Metformin in Subjects With Type 2 Diabetes (NCT NCT03136484)

Last Updated: 2020-01-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

788 participants

Primary outcome timeframe

Week 0, week 52

Results posted on

2020-01-21

Participant Flow

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).

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

Participant milestones

Participant milestones
Measure	Semaglutide + Canagliflozin Placebo 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.	Canagliflozin + Semaglutide Placebo Participants received canagliflozin tablet once-daily orally for 52 weeks: 100 mg tablet during 0-8 weeks followed by 300 mg tablet during 9-52 weeks. Participants also received placebo matched to semaglutide s.c. injection once-weekly for 52 weeks.
Overall Study STARTED	394	394
Overall Study Exposed	392	394
Overall Study COMPLETED	367	372
Overall Study NOT COMPLETED	27	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Semaglutide + Canagliflozin Placebo 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.	Canagliflozin + Semaglutide Placebo Participants received canagliflozin tablet once-daily orally for 52 weeks: 100 mg tablet during 0-8 weeks followed by 300 mg tablet during 9-52 weeks. Participants also received placebo matched to semaglutide s.c. injection once-weekly for 52 weeks.
Overall Study Withdrawal by Subject	19	14
Overall Study Lost to Follow-up	7	8
Overall Study Death	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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 n=788 Participants Total of all reporting groups
Age, Continuous	55.7 Years STANDARD_DEVIATION 11.1 • n=5 Participants	57.5 Years STANDARD_DEVIATION 10.7 • n=7 Participants	56.6 Years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	171 Participants n=5 Participants	193 Participants n=7 Participants	364 Participants n=5 Participants
Sex: Female, Male Male	223 Participants n=5 Participants	201 Participants n=7 Participants	424 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	156 Participants n=5 Participants	137 Participants n=7 Participants	293 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	238 Participants n=5 Participants	257 Participants n=7 Participants	495 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race : American Indian or Alaska native	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race : Asian	62 Participants n=5 Participants	63 Participants n=7 Participants	125 Participants n=5 Participants
Race/Ethnicity, Customized Race : Black or African American	28 Participants n=5 Participants	30 Participants n=7 Participants	58 Participants n=5 Participants
Race/Ethnicity, Customized Race : Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race : White	297 Participants n=5 Participants	290 Participants n=7 Participants	587 Participants n=5 Participants
Race/Ethnicity, Customized Race : Other	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Race : Not Applicable	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
HbA1c	8.3 Percentage (%) of HbA1c STANDARD_DEVIATION 1.0 • n=5 Participants	8.2 Percentage (%) of HbA1c STANDARD_DEVIATION 1.0 • n=7 Participants	8.3 Percentage (%) of HbA1c STANDARD_DEVIATION 1.0 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, week 52

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

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in HbA1c On-treatment without rescue medication	-1.7 Percentage (%) of HbA1c Standard Deviation 1.1	-1.0 Percentage (%) of HbA1c Standard Deviation 1.0
Change in HbA1c In-trial	-1.5 Percentage (%) of HbA1c Standard Deviation 1.3	-1.0 Percentage (%) of HbA1c Standard Deviation 1.1

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Body Weight (kg)	-5.7 Kilogram (kg) Standard Deviation 5.4	-4.3 Kilogram (kg) Standard Deviation 4.0

SECONDARY outcome

Timeframe: Week 0, week 52

Population: Dual X-ray absorptiometry (DXA) analysis set comprised of all randomised participants who are included in the body composition sub-study. "Number analyzed"=participants with available data.

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=88 Participants 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.	Canagliflozin + Semaglutide Placebo n=90 Participants 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.
Change in Total Fat Mass (kg)	-3.72 kg Standard Deviation 4.50	-2.63 kg Standard Deviation 3.30

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in FPG (Fasting Plasma Glucose)	-2.54 Millimoles per liter (mmol/L) Standard Deviation 2.77	-2.00 Millimoles per liter (mmol/L) Standard Deviation 2.53

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in SMPG (Self-measured Plasma Glucose)- Mean 7-point Profile	-2.8 mmol/L Standard Deviation 2.3	-1.9 mmol/L Standard Deviation 2.7

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in SMPG- Mean Postprandial Increment Over All Meals	-0.6 mmol/L Standard Deviation 2.1	-0.6 mmol/L Standard Deviation 2.0

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Fasting Total Cholesterol	0.96 Ratio of total cholesterol Geometric Coefficient of Variation 19.3	1.03 Ratio of total cholesterol Geometric Coefficient of Variation 18.2

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Fasting LDL-cholesterol	0.96 Ratio of LDL-cholesterol Geometric Coefficient of Variation 32.2	1.05 Ratio of LDL-cholesterol Geometric Coefficient of Variation 29.0

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Fasting HDL-cholesterol	1.04 Ratio of HDL-cholesterol Geometric Coefficient of Variation 13.1	1.08 Ratio of HDL-cholesterol Geometric Coefficient of Variation 13.6

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Fasting Triglycerides	0.86 Ratio of triglycerides Geometric Coefficient of Variation 40.6	0.92 Ratio of triglycerides Geometric Coefficient of Variation 38.2

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) Systolic blood pressure	-3.7 Millimeters of mercury (mmHg) Standard Deviation 14.0	-5.8 Millimeters of mercury (mmHg) Standard Deviation 13.5
Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) Diastolic blood pressure	-1.2 Millimeters of mercury (mmHg) Standard Deviation 9.8	-2.9 Millimeters of mercury (mmHg) Standard Deviation 9.0

SECONDARY outcome

Timeframe: Week 0, week 52

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

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Percentage Change in Body Weight (%)	-6.2 Percentage change Standard Deviation 6.1	-4.7 Percentage change Standard Deviation 4.0

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Body Mass Index (BMI)	-2.0 Kilogram per square meter (kg/m^2) Standard Deviation 2.0	-1.5 Kilogram per square meter (kg/m^2) Standard Deviation 1.4

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Waist Circumference	-4.2 Centimeter (cm) Standard Deviation 6.2	-3.0 Centimeter (cm) Standard Deviation 5.4

SECONDARY outcome

Timeframe: Week 0, week 52

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

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=88 Participants 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.	Canagliflozin + Semaglutide Placebo n=90 Participants 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.
Percentage Change in Total Fat Mass (%)	-1.55 Percentage change Standard Deviation 2.76	-1.21 Percentage change Standard Deviation 2.64

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=88 Participants 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.	Canagliflozin + Semaglutide Placebo n=90 Participants 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.
Change in Total Lean Mass (kg)	-2.06 kg Standard Deviation 2.15	-1.53 kg Standard Deviation 2.21

SECONDARY outcome

Timeframe: Week 0, week 52

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

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=88 Participants 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.	Canagliflozin + Semaglutide Placebo n=90 Participants 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.
Percentage Change in Total Lean Mass (%)	1.38 Percentage change Standard Deviation 2.66	1.09 Percentage change Standard Deviation 2.56

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=88 Participants 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.	Canagliflozin + Semaglutide Placebo n=90 Participants 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.
Change in Visceral Fat Mass (kg)	-0.20 kg Standard Deviation 0.40	-0.13 kg Standard Deviation 0.32

SECONDARY outcome

Timeframe: Week 0, week 52

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

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=88 Participants 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.	Canagliflozin + Semaglutide Placebo n=90 Participants 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.
Percentage Change in Visceral Fat Mass (%)	-0.81 Percentage change Standard Deviation 7.30	0.16 Percentage change Standard Deviation 4.36

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=88 Participants 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.	Canagliflozin + Semaglutide Placebo n=90 Participants 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.
Change in Ratio Between Total Fat Mass and Total Lean Mass	-0.04 total fat mass/total lean mass ratio Standard Deviation 0.08	-0.03 total fat mass/total lean mass ratio Standard Deviation 0.07

SECONDARY outcome

Timeframe: Week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=293 Participants 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.	Canagliflozin + Semaglutide Placebo n=313 Participants 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.
Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no) Yes	76.1 Percentage of participants	50.8 Percentage of participants
Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no) No	23.9 Percentage of participants	49.2 Percentage of participants

SECONDARY outcome

Timeframe: Week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=293 Participants 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.	Canagliflozin + Semaglutide Placebo n=313 Participants 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.
Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no) Yes	62.1 Percentage of participants	26.8 Percentage of participants
Participants Who Achieved HbA1c ≤ 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists (AACE) Target (Yes/no) No	37.9 Percentage of participants	73.2 Percentage of participants

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=293 Participants 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.	Canagliflozin + Semaglutide Placebo n=313 Participants 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.
Participants Who Achieved HbA1c Reduction ≥1% (Yes/no) Yes	76.5 Percentage of participants	48.6 Percentage of participants
Participants Who Achieved HbA1c Reduction ≥1% (Yes/no) No	23.5 Percentage of participants	51.4 Percentage of participants

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=298 Participants 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.	Canagliflozin + Semaglutide Placebo n=313 Participants 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.
Participants Who Achieved Weight Loss ≥3% (Yes/no) Yes	68.8 Percentage of participants	64.9 Percentage of participants
Participants Who Achieved Weight Loss ≥3% (Yes/no) No	31.2 Percentage of participants	35.1 Percentage of participants

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=298 Participants 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.	Canagliflozin + Semaglutide Placebo n=313 Participants 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.
Participants Who Achieved Weight Loss ≥5% (Yes/no) Yes	52.7 Percentage of participants	47.0 Percentage of participants
Participants Who Achieved Weight Loss ≥5% (Yes/no) No	47.3 Percentage of participants	53.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=298 Participants 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.	Canagliflozin + Semaglutide Placebo n=313 Participants 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.
Participants Who Achieved Weight Loss ≥10% (Yes/no) Yes	23.2 Percentage of participants	8.9 Percentage of participants
Participants Who Achieved Weight Loss ≥10% (Yes/no) No	76.8 Percentage of participants	91.1 Percentage of participants

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=293 Participants 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.	Canagliflozin + Semaglutide Placebo n=313 Participants 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.
Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/no) Yes	69.6 Percentage of participants	45.0 Percentage of participants
Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/no) No	30.4 Percentage of participants	55.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=293 Participants 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.	Canagliflozin + Semaglutide Placebo n=313 Participants 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.
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no) Yes	57.3 Percentage of participants	34.8 Percentage of participants
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥3% (Yes/no) No	42.7 Percentage of participants	65.2 Percentage of participants

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=293 Participants 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.	Canagliflozin + Semaglutide Placebo n=313 Participants 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.
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no) Yes	45.1 Percentage of participants	25.9 Percentage of participants
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥5% (Yes/no) No	54.9 Percentage of participants	74.1 Percentage of participants

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=293 Participants 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.	Canagliflozin + Semaglutide Placebo n=313 Participants 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.
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no) Yes	21.8 Percentage of participants	6.1 Percentage of participants
Participants Who Achieved HbA1c Reduction ≥1% and Weight Loss ≥10% (Yes/no) No	78.2 Percentage of participants	93.9 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 0-57

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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 Number of Treatment Emergent Adverse Events (TEAEs)	1189 Adverse events	1138 Adverse events

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Haematological Parameter- Haemoglobin	0.99 Ratio of haemoglobin Geometric Coefficient of Variation 8.0	1.05 Ratio of haemoglobin Geometric Coefficient of Variation 8.5

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Haematological Parameter- Haematocrit	0.99 Ratio of haematocrit Geometric Coefficient of Variation 6.8	1.04 Ratio of haematocrit Geometric Coefficient of Variation 6.9

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Haematological Parameter- Erythrocytes	0.99 Ratio of erythrocytes Geometric Coefficient of Variation 5.7	1.04 Ratio of erythrocytes Geometric Coefficient of Variation 6.0

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Haematological Parameter- Leukocytes	0.97 Ratio of leukocytes Geometric Coefficient of Variation 20.3	0.98 Ratio of leukocytes Geometric Coefficient of Variation 17.5

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Haematological Parameter- Thrombocytes	1.04 Ratio of thrombocytes Geometric Coefficient of Variation 14.4	1.00 Ratio of thrombocytes Geometric Coefficient of Variation 15.4

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- Amylase	1.16 Ratio of amylase Geometric Coefficient of Variation 26.5	1.09 Ratio of amylase Geometric Coefficient of Variation 24.4

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- Lipase	1.25 Ratio of lipase Geometric Coefficient of Variation 54.5	1.01 Ratio of lipase Geometric Coefficient of Variation 51.5

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- ALT	0.79 Ratio of ALT Geometric Coefficient of Variation 49.5	0.79 Ratio of ALT Geometric Coefficient of Variation 45.3

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- AST	0.89 Ratio of AST Geometric Coefficient of Variation 37.5	0.86 Ratio of AST Geometric Coefficient of Variation 37.4

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- ALP	0.96 Ratio of ALP Geometric Coefficient of Variation 19.6	0.95 Ratio of ALP Geometric Coefficient of Variation 16.8

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- Total Bilirubin	1.06 Ratio of total bilirubin Geometric Coefficient of Variation 32.1	1.13 Ratio of total bilirubin Geometric Coefficient of Variation 33.9

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- Creatinine	1.03 Ratio of creatinine Geometric Coefficient of Variation 11.0	1.04 Ratio of creatinine Geometric Coefficient of Variation 11.9

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- eGFR	0.98 Ratio of eGFR Geometric Coefficient of Variation 8.4	0.96 Ratio of eGFR Geometric Coefficient of Variation 9.7

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- Albumin	0.99 Ratio of albumin Geometric Coefficient of Variation 5.4	1.00 Ratio of albumin Geometric Coefficient of Variation 5.2

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- Calcium	1.01 Ratio of calcium Geometric Coefficient of Variation 4.5	1.02 Ratio of calcium Geometric Coefficient of Variation 4.1

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- Potassium	1.00 Ratio of potassium Geometric Coefficient of Variation 9.3	1.00 Ratio of potassium Geometric Coefficient of Variation 8.6

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Biochemistry Parameter- Sodium	1.00 Ratio of sodium Geometric Coefficient of Variation 1.6	1.00 Ratio of sodium Geometric Coefficient of Variation 1.5

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Calcitonin	1.08 Ratio of calcitonin Geometric Coefficient of Variation 43.8	1.04 Ratio of calcitonin Geometric Coefficient of Variation 35.6

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Pulse	2.7 Beats per minute (beats/min) Standard Deviation 9.5	-0.6 Beats per minute (beats/min) Standard Deviation 8.6

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in ECG Normal (week 52)	222 Participants	242 Participants
Change in ECG Normal (week 0)	263 Participants	277 Participants
Change in ECG Abnormal NCS (week 0)	126 Participants	117 Participants
Change in ECG Abnormal CS (week 0)	3 Participants	0 Participants
Change in ECG Abnormal NCS (week 52)	109 Participants	95 Participants
Change in ECG Abnormal CS (week 52)	0 Participants	3 Participants

SECONDARY outcome

Timeframe: Week -2, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Physical Examination Skin (week 52) Abnormal CS	1 Participants	1 Participants
Change in Physical Examination Respiratory System (week -2) Normal	383 Participants	391 Participants
Change in Physical Examination Respiratory System (week -2) Abnormal NCS	7 Participants	3 Participants
Change in Physical Examination Respiratory System (week -2) Abnormal CS	2 Participants	0 Participants
Change in Physical Examination Respiratory System (week 52) Normal	321 Participants	336 Participants
Change in Physical Examination Respiratory System (week 52) Abnormal NCS	4 Participants	3 Participants
Change in Physical Examination Respiratory System (week 52) Abnormal CS	1 Participants	0 Participants
Change in Physical Examination Lymph Node Palpation (week -2) Normal	390 Participants	392 Participants
Change in Physical Examination Lymph Node Palpation (week -2) Abnormal NCS	1 Participants	2 Participants
Change in Physical Examination Lymph Node Palpation (week -2) Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Lymph Node Palpation (week 52) Normal	325 Participants	337 Participants
Change in Physical Examination Lymph Node Palpation (week 52) Abnormal NCS	0 Participants	0 Participants
Change in Physical Examination Lymph Node Palpation (week 52) Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Thyroid Gland (week -2) Normal	390 Participants	390 Participants
Change in Physical Examination Thyroid Gland (week -2) Abnormal NCS	2 Participants	4 Participants
Change in Physical Examination Thyroid Gland (week -2) Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Thyroid Gland (week 52) Normal	326 Participants	337 Participants
Change in Physical Examination Thyroid Gland (week 52) Abnormal NCS	0 Participants	1 Participants
Change in Physical Examination Thyroid Gland (week 52) Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Left foot (week -2) Normal	343 Participants	345 Participants
Change in Physical Examination Left foot (week -2) Abnormal NCS	47 Participants	44 Participants
Change in Physical Examination Left foot (week -2) Abnormal CS	2 Participants	5 Participants
Change in Physical Examination Left foot (week 52) Normal	293 Participants	303 Participants
Change in Physical Examination Left foot (week 52) Abnormal NCS	32 Participants	34 Participants
Change in Physical Examination Left foot (week 52) Abnormal CS	1 Participants	2 Participants
Change in Physical Examination Right foot (week -2) Normal	344 Participants	348 Participants
Change in Physical Examination Right foot (week -2) Abnormal NCS	45 Participants	42 Participants
Change in Physical Examination Right foot (week -2) Abnormal CS	3 Participants	4 Participants
Change in Physical Examination Right foot (week 52) Normal	289 Participants	304 Participants
Change in Physical Examination Right foot (week 52) Abnormal NCS	34 Participants	32 Participants
Change in Physical Examination Right foot (week 52) Abnormal CS	3 Participants	3 Participants
Change in Physical Examination Left leg (week -2) Normal	348 Participants	358 Participants
Change in Physical Examination Left leg (week -2) Abnormal NCS	40 Participants	30 Participants
Change in Physical Examination Left leg (week -2) Abnormal CS	4 Participants	6 Participants
Change in Physical Examination Left leg (week 52) Normal	300 Participants	314 Participants
Change in Physical Examination Left leg (week 52) Abnormal NCS	22 Participants	22 Participants
Change in Physical Examination Left leg (week 52) Abnormal CS	4 Participants	3 Participants
Change in Physical Examination Right leg (week -2) Normal	350 Participants	357 Participants
Change in Physical Examination Right leg (week -2) Abnormal NCS	37 Participants	30 Participants
Change in Physical Examination Right leg (week -2) Abnormal CS	5 Participants	7 Participants
Change in Physical Examination Right leg (week 52) Normal	301 Participants	315 Participants
Change in Physical Examination Right leg (week 52) Abnormal NCS	19 Participants	21 Participants
Change in Physical Examination Right leg (week 52) Abnormal CS	6 Participants	3 Participants
Change in Physical Examination General Appearance (week -2) Normal	345 Participants	335 Participants
Change in Physical Examination General Appearance (week -2) Abnormal NCS	46 Participants	56 Participants
Change in Physical Examination General Appearance (week -2) Abnormal CS	1 Participants	3 Participants
Change in Physical Examination General Appearance (week 52) Normal	294 Participants	304 Participants
Change in Physical Examination General Appearance (week 52) Abnormal NCS	30 Participants	33 Participants
Change in Physical Examination General Appearance (week 52) Abnormal CS	2 Participants	2 Participants
Change in Physical Examination Nervous System (week -2) Normal	360 Participants	370 Participants
Change in Physical Examination Nervous System (week -2) Abnormal NCS	26 Participants	21 Participants
Change in Physical Examination Nervous System (week -2) Abnormal CS	5 Participants	3 Participants
Change in Physical Examination Nervous System (week 52) Normal	303 Participants	325 Participants
Change in Physical Examination Nervous System (week 52) Abnormal NCS	21 Participants	12 Participants
Change in Physical Examination Nervous System (week 52) Abnormal CS	2 Participants	2 Participants
Change in Physical Examination Cardiovascular System (week-2) Normal	376 Participants	386 Participants
Change in Physical Examination Cardiovascular System (week -2) Abnormal NCS	15 Participants	8 Participants
Change in Physical Examination Cardiovascular System (week -2) Abnormal CS	1 Participants	0 Participants
Change in Physical Examination Cardiovascular System (week52) Normal	318 Participants	333 Participants
Change in Physical Examination Cardiovascular System (week 52) Abnormal NCS	7 Participants	6 Participants
Change in Physical Examination Cardiovascular System (week 52) Abnormal CS	1 Participants	0 Participants
Change in Physical Examination Gastrointestinal System (week -2) Normal	369 Participants	377 Participants
Change in Physical Examination Gastrointestinal System (week -2) Abnormal NCS	22 Participants	16 Participants
Change in Physical Examination Gastrointestinal System (week -2) Abnormal CS	1 Participants	1 Participants
Change in Physical Examination Gastrointestinal System (week 52) Normal	319 Participants	331 Participants
Change in Physical Examination Gastrointestinal System (week 52) Abnormal NCS	7 Participants	8 Participants
Change in Physical Examination Gastrointestinal System (week 52) Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Skin (week -2) Normal	330 Participants	323 Participants
Change in Physical Examination Skin (week -2) Abnormal NCS	62 Participants	69 Participants
Change in Physical Examination Skin (week -2) Abnormal CS	0 Participants	2 Participants
Change in Physical Examination Skin (week 52) Normal	286 Participants	298 Participants
Change in Physical Examination Skin (week 52) Abnormal NCS	39 Participants	40 Participants

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Eye Examination Left eye: Normal (week 0)	322 Participants	319 Participants
Eye Examination Left eye: Abnormal NCS (week 0)	65 Participants	71 Participants
Eye Examination Left eye: Abnormal CS (week 0)	5 Participants	3 Participants
Eye Examination Left eye: Normal (week 52)	231 Participants	228 Participants
Eye Examination Left eye: Abnormal NCS (week 52)	30 Participants	40 Participants
Eye Examination Left eye: Abnormal CS (week 52)	7 Participants	2 Participants
Eye Examination Right eye: Normal (week 0)	321 Participants	319 Participants
Eye Examination Right eye: Abnormal NCS (week 0)	66 Participants	70 Participants
Eye Examination Right eye: Abnormal CS (week 0)	5 Participants	4 Participants
Eye Examination Right eye: Normal (week 52)	225 Participants	226 Participants
Eye Examination Right eye: Abnormal NCS (week 52)	35 Participants	44 Participants
Eye Examination Right eye: Abnormal CS (week 52)	8 Participants	0 Participants

SECONDARY outcome

Timeframe: Weeks 0-57

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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 Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes	25 Episodes	6 Episodes

SECONDARY outcome

Timeframe: Weeks 0-57

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=392 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes	6 Participants	5 Participants

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Short Form 36 Health Survey (SF-36): Sub-domains Physical Functioning	1.9 Score on a scale Standard Deviation 7.1	2.7 Score on a scale Standard Deviation 6.7
Change in Short Form 36 Health Survey (SF-36): Sub-domains Role-physical	1.8 Score on a scale Standard Deviation 7.3	2.0 Score on a scale Standard Deviation 7.1
Change in Short Form 36 Health Survey (SF-36): Sub-domains Bodily pain	2.5 Score on a scale Standard Deviation 8.9	1.5 Score on a scale Standard Deviation 8.7
Change in Short Form 36 Health Survey (SF-36): Sub-domains General health	3.7 Score on a scale Standard Deviation 7.7	3.5 Score on a scale Standard Deviation 8.5
Change in Short Form 36 Health Survey (SF-36): Sub-domains Social functioning	1.1 Score on a scale Standard Deviation 8.6	1.1 Score on a scale Standard Deviation 8.0
Change in Short Form 36 Health Survey (SF-36): Sub-domains Role-emotional	0.8 Score on a scale Standard Deviation 9.2	1.2 Score on a scale Standard Deviation 8.6
Change in Short Form 36 Health Survey (SF-36): Sub-domains Vitality	3.0 Score on a scale Standard Deviation 8.2	2.0 Score on a scale Standard Deviation 8.2
Change in Short Form 36 Health Survey (SF-36): Sub-domains Mental health	1.5 Score on a scale Standard Deviation 8.3	0.6 Score on a scale Standard Deviation 8.1

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in SF-36: Physical Component Summary (PCS)	2.7 Score on a scale Standard Deviation 6.7	2.9 Score on a scale Standard Deviation 6.2

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in SF-36: Mental Component Summary (MCS)	1.1 Score on a scale Standard Deviation 8.8	0.5 Score on a scale Standard Deviation 8.0

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately 1) Satisfaction with treatment	1.4 Score on a scale Standard Deviation 1.6	1.0 Score on a scale Standard Deviation 1.6
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately 2) Feeling of unacceptably high blood sugars	-2.0 Score on a scale Standard Deviation 2.2	-1.8 Score on a scale Standard Deviation 2.2
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately 3) Feeling of unacceptably low blood sugars	0.1 Score on a scale Standard Deviation 1.9	0.1 Score on a scale Standard Deviation 1.6
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately 4) Convenience of treatment	0.8 Score on a scale Standard Deviation 1.8	0.7 Score on a scale Standard Deviation 1.8
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately 5) Flexibility of current treatment	0.8 Score on a scale Standard Deviation 1.7	0.7 Score on a scale Standard Deviation 1.7
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately 6) Satisfaction with understanding of diabetes	0.8 Score on a scale Standard Deviation 1.5	0.6 Score on a scale Standard Deviation 1.3
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately 7) Recommending treatment to others	0.9 Score on a scale Standard Deviation 1.5	0.9 Score on a scale Standard Deviation 1.5
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately 8) Satisfaction to continue with present treatment	1.1 Score on a scale Standard Deviation 1.8	0.8 Score on a scale Standard Deviation 1.8
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Summary Score (Sum of 6 of 8 Items) and the 8 Items Separately Total treatment satisfaction score	5.8 Score on a scale Standard Deviation 7.0	4.8 Score on a scale Standard Deviation 7.2

SECONDARY outcome

Timeframe: Week 0, week 52

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

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.

Outcome measures

Outcome measures
Measure	Semaglutide + Canagliflozin Placebo n=394 Participants 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.	Canagliflozin + Semaglutide Placebo n=394 Participants 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.
Change in Control of Eating Questionnaire (CoEQ): Domains Craving control	1.0 Score on a scale Standard Deviation 2.1	1.0 Score on a scale Standard Deviation 2.5
Change in Control of Eating Questionnaire (CoEQ): Domains Craving for sweet	-0.6 Score on a scale Standard Deviation 2.2	-0.6 Score on a scale Standard Deviation 2.1
Change in Control of Eating Questionnaire (CoEQ): Domains Craving for savoury	-1.1 Score on a scale Standard Deviation 2.0	-0.9 Score on a scale Standard Deviation 2.0
Change in Control of Eating Questionnaire (CoEQ): Domains Positive mood	0.7 Score on a scale Standard Deviation 1.7	0.4 Score on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: Week 0, week 52

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

Outcome measures

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

Adverse Events

Semaglutide + Canagliflozin Placebo

Serious events: 18 serious events

Other events: 185 other events

Deaths: 1 deaths

Canagliflozin + Semaglutide Placebo

Serious events: 21 serious events

Other events: 120 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Semaglutide + Canagliflozin Placebo n=392 participants at risk 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.	Canagliflozin + Semaglutide Placebo n=394 participants at risk 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.
Musculoskeletal and connective tissue disorders Back pain	2.8% 11/392 • Number of events 11 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.	5.3% 21/394 • Number of events 21 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.
Gastrointestinal disorders Constipation	5.1% 20/392 • Number of events 20 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.	5.8% 23/394 • Number of events 23 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.
Metabolism and nutrition disorders Decreased appetite	6.6% 26/392 • Number of events 26 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.	1.5% 6/394 • Number of events 6 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.
Gastrointestinal disorders Diarrhoea	15.1% 59/392 • Number of events 94 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.	9.4% 37/394 • Number of events 58 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.
Gastrointestinal disorders Dyspepsia	5.6% 22/392 • Number of events 23 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.	2.0% 8/394 • Number of events 8 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.
Nervous system disorders Headache	6.6% 26/392 • Number of events 48 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.	6.9% 27/394 • Number of events 47 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.
Infections and infestations Nasopharyngitis	5.9% 23/392 • Number of events 25 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.	6.6% 26/394 • Number of events 34 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.
Gastrointestinal disorders Nausea	22.7% 89/392 • Number of events 127 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.	6.6% 26/394 • Number of events 30 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.
Gastrointestinal disorders Vomiting	12.8% 50/392 • Number of events 77 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.	2.3% 9/394 • Number of events 9 • From the date of first dose of trial product (week 0) to end of treatment (week 52) + post treatment follow-up of 5 weeks. 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.

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER