Trial Outcomes & Findings for Efficacy and Safety of Oral Semaglutide Versus Empagliflozin in Subjects With Type 2 Diabetes Mellitus (NCT NCT02863328)

Last Updated: 2022-07-20

Results Overview

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

822 participants

Primary outcome timeframe

Week 0, week 26

Results posted on

2022-07-20

Participant Flow

The trial was conducted at 108 sites in 12 countries as follows: Argentina (4), Brazil (3), Croatia (4), Greece (7), Hungary (7), Italy (5), Poland (6), Russian Federation (6), Serbia (5), Spain (8), Thailand (3), United States (46). 1 site each in Croatia and Italy, and 2 sites in the United States screened, but didn't randomise any subjects.

Data presented in "participant flow" is based on the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participant milestones

Participant milestones
Measure	Oral Semaglutide 14 mg Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Overall Study STARTED	411	410
Overall Study Full Analysis Set (FAS)	411	410
Overall Study Safety Analysis Set (SAS)	410	409
Overall Study COMPLETED	400	387
Overall Study NOT COMPLETED	11	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Oral Semaglutide 14 mg Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Overall Study Lost to Follow-up	4	10
Overall Study Withdrawal by Subject	7	12
Overall Study Died	0	1

Baseline Characteristics

Efficacy and Safety of Oral Semaglutide Versus Empagliflozin in Subjects With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.	Total n=821 Participants Total of all reporting groups
Age, Continuous	57 years STANDARD_DEVIATION 10 • n=5 Participants	58 years STANDARD_DEVIATION 10 • n=7 Participants	58 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	205 Participants n=5 Participants	201 Participants n=7 Participants	406 Participants n=5 Participants
Sex: Female, Male Male	206 Participants n=5 Participants	209 Participants n=7 Participants	415 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	91 Participants n=5 Participants	108 Participants n=7 Participants	199 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	320 Participants n=5 Participants	302 Participants n=7 Participants	622 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 · White	355 Participants n=5 Participants	353 Participants n=7 Participants	708 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	26 Participants n=5 Participants	33 Participants n=7 Participants	59 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	28 Participants n=5 Participants	21 Participants n=7 Participants	49 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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 · Other	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
HbA1c	8.1 percentage of HbA1c STANDARD_DEVIATION 0.9 • n=5 Participants	8.1 percentage of HbA1c STANDARD_DEVIATION 0.9 • n=7 Participants	8.1 percentage of HbA1c STANDARD_DEVIATION 0.9 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, week 26

Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in HbA1c In-trial	-1.3 Percentage-point of HbA1c Standard Deviation 1.1	-0.9 Percentage-point of HbA1c Standard Deviation 0.9
Change in HbA1c On-treatment without rescue medication	-1.5 Percentage-point of HbA1c Standard Deviation 1.1	-0.9 Percentage-point of HbA1c Standard Deviation 0.9

SECONDARY outcome

Timeframe: Week 0, week 26

Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS. Number Analyzed = number of participants with available data.

Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Body Weight (Kg) In-trial	-3.9 Kilogram (Kg) Standard Deviation 4.4	-3.8 Kilogram (Kg) Standard Deviation 3.8
Change in Body Weight (Kg) On-treatment without rescue medication	-4.3 Kilogram (Kg) Standard Deviation 4.4	-3.9 Kilogram (Kg) Standard Deviation 3.8

SECONDARY outcome

Timeframe: Week 0, week 52

Population: Overall number of participants analyzed = number of participants with available data.

Change from baseline (week 0) in HbA1c was evaluated at week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=384 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=382 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in HbA1c (%)	-1.3 Percentage of HbA1c Standard Deviation 1.2 • Interval 1.2 to	-0.9 Percentage of HbA1c Standard Deviation 1.0 • Interval 1.0 to

SECONDARY outcome

Timeframe: Week 0, week 52

Population: Overall number of participants analyzed = number of participants with available data.

Change from baseline (week 0) in body weight was evaluated at week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=386 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=383 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Body Weight (kg)	-4.0 Kg Standard Deviation 5.5 • Interval 5.5 to	-3.7 Kg Standard Deviation 4.3 • Interval 4.3 to

SECONDARY outcome

Timeframe: Week 0, week 26, week 52

Change from baseline (week 0) in fasting plasma glucose was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Fasting Plasma Glucose Week 26	-2.01 Millimoles per liter (mmol/L) Standard Deviation 2.56	-2.08 Millimoles per liter (mmol/L) Standard Deviation 2.17
Change in Fasting Plasma Glucose Week 52	-2.04 Millimoles per liter (mmol/L) Standard Deviation 2.50	-2.14 Millimoles per liter (mmol/L) Standard Deviation 2.36

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in mean of the 7-point self-measured plasma glucose (SMPG) (i.e. before and after breakfast, lunch and dinner, and at bedtime) profile was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in SMPG : Mean of the 7-point Profile Week 26	-2.3 mmol/L Standard Deviation 2.1	-1.9 mmol/L Standard Deviation 2.1
Change in SMPG : Mean of the 7-point Profile Week 52	-2.3 mmol/L Standard Deviation 2.3	-2.1 mmol/L Standard Deviation 2.3

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in mean postprandial glucose increment was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in SMPG : Mean Postprandial Increment Over All Meals Week 26	-0.5 mmol/L Standard Deviation 1.8	-0.4 mmol/L Standard Deviation 2.0
Change in SMPG : Mean Postprandial Increment Over All Meals Week 52	-0.6 mmol/L Standard Deviation 1.8	-0.4 mmol/L Standard Deviation 1.9

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in fasting C-peptide (Nanomoles per liter \[nmol/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Fasting C-peptide (Ratio to Baseline) week 26	1.10 Ratio of C-peptide Geometric Coefficient of Variation 35.7	0.89 Ratio of C-peptide Geometric Coefficient of Variation 29.4
Change in Fasting C-peptide (Ratio to Baseline) week 52	1.09 Ratio of C-peptide Geometric Coefficient of Variation 37.2	0.92 Ratio of C-peptide Geometric Coefficient of Variation 31.6

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in fasting insulin (picomoles per liter \[pmol/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Fasting Insulin (Ratio to Baseline) Week 26	1.06 Ratio of insulin Geometric Coefficient of Variation 50.5	0.77 Ratio of insulin Geometric Coefficient of Variation 54.1
Change in Fasting Insulin (Ratio to Baseline) Week 52	1.03 Ratio of insulin Geometric Coefficient of Variation 52.8	0.77 Ratio of insulin Geometric Coefficient of Variation 53.7

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in fasting pro-insulin (pmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Fasting Pro-insulin (Ratio to Baseline) Week 26	0.72 Ratio of pro-insulin Geometric Coefficient of Variation 74.6	0.66 Ratio of pro-insulin Geometric Coefficient of Variation 61.9
Change in Fasting Pro-insulin (Ratio to Baseline) Week 52	0.74 Ratio of pro-insulin Geometric Coefficient of Variation 80.5	0.69 Ratio of pro-insulin Geometric Coefficient of Variation 57.8

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in fasting glucagon (picograms per milliliter \[pg/mL\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Fasting Glucagon (Ratio to Baseline) Week 52	0.89 Ratio of glucagon Geometric Coefficient of Variation 27.8	0.95 Ratio of glucagon Geometric Coefficient of Variation 27.6
Change in Fasting Glucagon (Ratio to Baseline) Week 26	0.91 Ratio of glucagon Geometric Coefficient of Variation 28.0	1.01 Ratio of glucagon Geometric Coefficient of Variation 27.5

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in homeostatic model assessment index of insulin resistance (HOMA-IR) (%) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in HOMA-IR (Ratio to Baseline) Week 26	0.83 Ratio of HOMA-IR Geometric Coefficient of Variation 63.8	0.61 Ratio of HOMA-IR Geometric Coefficient of Variation 58.7
Change in HOMA-IR (Ratio to Baseline) Week 52	0.81 Ratio of HOMA-IR Geometric Coefficient of Variation 64.9	0.60 Ratio of HOMA-IR Geometric Coefficient of Variation 60.4

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in homeostatic model assessment index of beta-cell function (HOMA-B) (%) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in HOMA-B (Ratio to Baseline) Week 26	1.67 Ratio of HOMA-B Geometric Coefficient of Variation 69.5	1.16 Ratio of HOMA-B Geometric Coefficient of Variation 65.0
Change in HOMA-B (Ratio to Baseline) Week 52	1.66 Ratio of HOMA-B Geometric Coefficient of Variation 72.9	1.17 Ratio of HOMA-B Geometric Coefficient of Variation 69.9

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in C-reactive protein (milligrams per liter \[mg/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in C-reactive Protein (Ratio to Baseline) Week 26	0.69 Ratio of C-reactive protein Geometric Coefficient of Variation 121.5	0.98 Ratio of C-reactive protein Geometric Coefficient of Variation 115.7
Change in C-reactive Protein (Ratio to Baseline) Week 52	0.68 Ratio of C-reactive protein Geometric Coefficient of Variation 129.7	0.90 Ratio of C-reactive protein Geometric Coefficient of Variation 126.3

SECONDARY outcome

Timeframe: Week 0, week 26, week 52

Relative change from baseline (week 0) in body weight (kg) was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Body Weight (%) Week 26	-4.34 Percentage change Standard Deviation 4.51	-4.14 Percentage change Standard Deviation 4.12
Change in Body Weight (%) Week 52	-4.38 Percentage change Standard Deviation 5.76	-4.09 Percentage change Standard Deviation 4.78

SECONDARY outcome

Timeframe: Week 0, week 26, week 52

Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Body Mass Index Week 26	-1.4 Kilograms per square meter (kg/m^2) Standard Deviation 1.6	-1.4 Kilograms per square meter (kg/m^2) Standard Deviation 1.4
Change in Body Mass Index Week 52	-1.5 Kilograms per square meter (kg/m^2) Standard Deviation 2.0	-1.4 Kilograms per square meter (kg/m^2) Standard Deviation 1.6

SECONDARY outcome

Timeframe: Week 0, week 26, week 52

Change from baseline (week 0) in waist circumference was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Waist Circumference Week 26	-3.9 Centimetre (cm) Standard Deviation 5.1	-2.9 Centimetre (cm) Standard Deviation 5.0
Change in Waist Circumference Week 52	-3.7 Centimetre (cm) Standard Deviation 5.5	-2.9 Centimetre (cm) Standard Deviation 5.8

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in fasting total cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Fasting Total Cholesterol (Ratio to Baseline) Week 26	0.96 Ratio of total cholesterol Geometric Coefficient of Variation 18.1	1.02 Ratio of total cholesterol Geometric Coefficient of Variation 15.2
Change in Fasting Total Cholesterol (Ratio to Baseline) Week 52	0.97 Ratio of total cholesterol Geometric Coefficient of Variation 18.1	1.01 Ratio of total cholesterol Geometric Coefficient of Variation 17.1

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in fasting low density lipoprotein (LDL) cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Fasting LDL Cholesterol (Ratio to Baseline) Week 26	0.96 Ratio of LDL cholesterol Geometric Coefficient of Variation 38.3	1.03 Ratio of LDL cholesterol Geometric Coefficient of Variation 24.6
Change in Fasting LDL Cholesterol (Ratio to Baseline) Week 52	0.97 Ratio of LDL cholesterol Geometric Coefficient of Variation 30.1	1.03 Ratio of LDL cholesterol Geometric Coefficient of Variation 27.2

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in fasting high density lipoprotein (HDL) cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Fasting HDL Cholesterol (Ratio to Baseline) Week 26	1.01 Ratio of HDL cholesterol Geometric Coefficient of Variation 13.0	1.07 Ratio of HDL cholesterol Geometric Coefficient of Variation 15.9
Change in Fasting HDL Cholesterol (Ratio to Baseline) Week 52	1.01 Ratio of HDL cholesterol Geometric Coefficient of Variation 13.9	1.06 Ratio of HDL cholesterol Geometric Coefficient of Variation 14.0

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in fasting very low density lipoprotein (VLDL) cholesterol (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Fasting VLDL Cholesterol (Ratio to Baseline) Week 52	0.89 Ratio of VLDL cholesterol Geometric Coefficient of Variation 39.3	0.90 Ratio of VLDL cholesterol Geometric Coefficient of Variation 37.6
Change in Fasting VLDL Cholesterol (Ratio to Baseline) Week 26	0.89 Ratio of VLDL cholesterol Geometric Coefficient of Variation 39.0	0.91 Ratio of VLDL cholesterol Geometric Coefficient of Variation 34.7

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in fasting free fatty acids (FFA) (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. Because of an issue with the handling of the blood samples for FFA, all FFA data are considered invalid for this trial; thus, no conclusion with regards to FFA levels can be made based on the FFA data. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Fasting Free Fatty Acids (Ratio to Baseline) Week 26	0.95 Ratio of FFA Geometric Coefficient of Variation 51.3	1.05 Ratio of FFA Geometric Coefficient of Variation 46.9
Change in Fasting Free Fatty Acids (Ratio to Baseline) Week 52	0.88 Ratio of FFA Geometric Coefficient of Variation 53.0	0.97 Ratio of FFA Geometric Coefficient of Variation 49.2

SECONDARY outcome

Timeframe: Week 0, week 26 and week 52

Change from baseline (week 0) in fasting triglycerides (mmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Fasting Triglycerides (Ratio to Baseline) Week 26	0.88 Ratio of triglycerides Geometric Coefficient of Variation 40.5	0.90 Ratio of triglycerides Geometric Coefficient of Variation 36.1
Change in Fasting Triglycerides (Ratio to Baseline) Week 52	0.89 Ratio of triglycerides Geometric Coefficient of Variation 42.3	0.90 Ratio of triglycerides Geometric Coefficient of Variation 39.3

SECONDARY outcome

Timeframe: Week 26 and week 52

Participants who achieved HbA1c \<7.0% (53 mmol/mol) (American Diabetes Association (ADA) target) at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) Week 26 · Yes	262 Participants	158 Participants
Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) Week 26 · No	130 Participants	237 Participants
Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) Week 52 · Yes	254 Participants	165 Participants
Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) Week 52 · No	130 Participants	217 Participants

SECONDARY outcome

Timeframe: Week 26 and week 52

Participants who achieved HbA1c ≤6.5% (48 mmol/mol) (American Association of Clinical Endocrinologists (AACE) target) at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) Week 26 · Yes	186 Participants	68 Participants
Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) Week 26 · No	206 Participants	327 Participants
Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) Week 52 · Yes	182 Participants	83 Participants
Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) Week 52 · No	202 Participants	299 Participants

SECONDARY outcome

Timeframe: Week 26 and week 52

Participants who achieved weight loss of ≥5% at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Participants Who Achieve Weight Loss ≥5% (Yes/no) Week 26 · Yes	162 Participants	143 Participants
Participants Who Achieve Weight Loss ≥5% (Yes/no) Week 26 · No	231 Participants	253 Participants
Participants Who Achieve Weight Loss ≥5% (Yes/no) Week 52 · Yes	156 Participants	150 Participants
Participants Who Achieve Weight Loss ≥5% (Yes/no) Week 52 · No	230 Participants	233 Participants

SECONDARY outcome

Timeframe: Week 26 and week 52

Participants who achieved weight loss of ≥10% at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Participants Who Achieve Weight Loss ≥10% (Yes/no) Week 26 · Yes	49 Participants	27 Participants
Participants Who Achieve Weight Loss ≥10% (Yes/no) Week 26 · No	344 Participants	369 Participants
Participants Who Achieve Weight Loss ≥10% (Yes/no) Week 52 · Yes	58 Participants	30 Participants
Participants Who Achieve Weight Loss ≥10% (Yes/no) Week 52 · No	328 Participants	353 Participants

SECONDARY outcome

Timeframe: Week 26 and week 52

Participants who achieved HbA1c \<7.0% (53 mmol/mol) without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain at week 26 and week 52. Severe or BG-confirmed symptomatic hypoglycaemia: an episode, that is severe according to the ADA classification or BG-confirmed by a plasma glucose value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) Week 26 · No	155 Participants	254 Participants
Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) Week 26 · Yes	237 Participants	141 Participants
Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) Week 52 · Yes	214 Participants	149 Participants
Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) Week 52 · No	170 Participants	233 Participants

SECONDARY outcome

Timeframe: Week 26 and week 52

Participants who achieved HbA1c reduction ≥1%-point and weight loss of ≥3% at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) week 26 · Yes	177 Participants	111 Participants
Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) week 26 · No	215 Participants	284 Participants
Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) week 52 · Yes	164 Participants	101 Participants
Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) week 52 · No	220 Participants	281 Participants

SECONDARY outcome

Timeframe: Weeks 0-52

Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS.

Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Additional anti-diabetic medication: use of new anti-diabetic medication for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 26/week 52), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Time to Additional Anti-diabetic Medication Week 0-26	17 Participants	13 Participants
Time to Additional Anti-diabetic Medication Week 0-52	52 Participants	56 Participants

SECONDARY outcome

Timeframe: Weeks 0-52

Population: Overall number of participants analyzed = FAS which comprised all randomised participants, however, one participant was randomised twice and thereby included only once in the FAS.

Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. Rescue medication: use of new antidiabetic medication as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period: the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Time to Rescue Medication Week 0-26	8 Participants	5 Participants
Time to Rescue Medication Week 0-52	31 Participants	44 Participants

SECONDARY outcome

Timeframe: Weeks 0-57

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants who received at least one dose of trial product.

A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) with onset in the on-treatment observation period (the time period where participants are considered treated with trial product) and was assessed up to approximately 57 weeks (52-week treatment period plus the 5-week follow-up period).

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=410 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=409 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Number of Treatment-emergent Adverse Events (TEAE)	1022 Events	948 Events

SECONDARY outcome

Timeframe: Week 0, week 26, week 52

Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.

Change from baseline (week 0) in amylase (units per liter \[U/L\]) at week 26 and week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=410 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=409 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Amylase (Ratio to Baseline) Week 26	1.15 Ratio of amylase Geometric Coefficient of Variation 30.1	1.10 Ratio of amylase Geometric Coefficient of Variation 24.8
Change in Amylase (Ratio to Baseline) Week 52	1.13 Ratio of amylase Geometric Coefficient of Variation 31.5	1.11 Ratio of amylase Geometric Coefficient of Variation 26.8

SECONDARY outcome

Timeframe: Week 0, week 26, week 52

Change from baseline (week 0) in lipase (U/L) at week 26 and week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=410 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=409 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Lipase (Ratio to Baseline) Week 26	1.37 Ratio of lipase Geometric Coefficient of Variation 62.0	1.10 Ratio of lipase Geometric Coefficient of Variation 50.8
Change in Lipase (Ratio to Baseline) Week 52	1.27 Ratio of lipase Geometric Coefficient of Variation 63.6	1.07 Ratio of lipase Geometric Coefficient of Variation 47.2

SECONDARY outcome

Timeframe: Week 0, week 26, week 52

Change from baseline (week 0) in pulse rate was evaluated at week 26 and week 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=410 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=409 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Pulse Rate Week 26	1 Beats/minute Standard Deviation 10	-2 Beats/minute Standard Deviation 9
Change in Pulse Rate Week 52	1 Beats/minute Standard Deviation 10	-2 Beats/minute Standard Deviation 9

SECONDARY outcome

Timeframe: Week 0, week 26, week 52

Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 26 and week 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=410 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=409 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) DBP, week 52	-3 Millimeters of mercury (mmHg) Standard Deviation 10	-3 Millimeters of mercury (mmHg) Standard Deviation 9
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) SBP, week 26	-5 Millimeters of mercury (mmHg) Standard Deviation 15	-5 Millimeters of mercury (mmHg) Standard Deviation 14
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) SBP, week 52	-5 Millimeters of mercury (mmHg) Standard Deviation 13	-4 Millimeters of mercury (mmHg) Standard Deviation 15
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) DBP, week 26	-2 Millimeters of mercury (mmHg) Standard Deviation 9	-3 Millimeters of mercury (mmHg) Standard Deviation 9

SECONDARY outcome

Timeframe: Week 0, week 26, week 52

Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at week 26 and week 52. Change from baseline results are presented as shift in findings (normal, abnormal and not clinically significant (NCS), and abnormal and clinically significant (CS)) from week 0 to week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=410 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=409 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in ECG Abnormal (week 0) NCS to abnormal CS (week 52)	1 Participants	2 Participants
Change in ECG Abnormal CS (week 0) to abnormal NCS (week 52)	2 Participants	0 Participants
Change in ECG Normal (week 0) to normal (week 26)	207 Participants	203 Participants
Change in ECG Normal (week 0) to abnormal NCS (week 26)	30 Participants	37 Participants
Change in ECG Normal (week 0) to abnormal CS (week 26)	1 Participants	2 Participants
Change in ECG Abnormal NCS (week 0) to normal (week 26)	50 Participants	41 Participants
Change in ECG Abnormal NCS (week 0) to abnormal NCS (week 26)	97 Participants	110 Participants
Change in ECG Abnormal NCS (week 0) to abnormal CS (week 26)	0 Participants	0 Participants
Change in ECG Abnormal CS (week 0) to normal (week 26)	1 Participants	0 Participants
Change in ECG Abnormal CS (week 0) CS to abnormal NCS (week 26)	2 Participants	0 Participants
Change in ECG Abnormal CS (week 0) to abnormal CS (week 26)	1 Participants	1 Participants
Change in ECG Normal (week 0) to normal (week 52)	196 Participants	194 Participants
Change in ECG Normal (week 0) to abnormal NCS (week 52)	39 Participants	39 Participants
Change in ECG Normal (week 0) to abnormal CS (week 52)	0 Participants	2 Participants
Change in ECG Abnormal (week 0) NCS to normal (week 52)	46 Participants	45 Participants
Change in ECG Abnormal (week 0) NCS to abnormal NCS (week 52)	98 Participants	97 Participants
Change in ECG Abnormal CS (week 0) to normal (week 52)	1 Participants	0 Participants
Change in ECG Abnormal CS (week 0) to abnormal CS (week 52)	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Week -2, week 52

The physical examination findings (normal, abnormal NCS and abnormal CS) of the participants at week -2 and week 52 are presented for the following examinations: Cardiovascular system, Nervous system (central and peripheral); Gastrointestinal system, incl. mouth; General appearance; Head (ears, eyes, nose), throat, neck; Lymph node palpation; Musculoskeletal system; Respiratory system; Skin; Thyroid gland. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=410 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=409 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Physical Examination Cardiovascular system (week -2) · Abnormal NCS	24 Participants	34 Participants
Change in Physical Examination Head, throat, neck (week -2) · Abnormal NCS	18 Participants	26 Participants
Change in Physical Examination Musculoskeletal system (week 52) · Abnormal NCS	15 Participants	20 Participants
Change in Physical Examination Cardiovascular system (week -2) · Normal	381 Participants	372 Participants
Change in Physical Examination Cardiovascular system (week -2) · Abnormal CS	5 Participants	3 Participants
Change in Physical Examination Cardiovascular system (week 52) · Normal	360 Participants	351 Participants
Change in Physical Examination Cardiovascular system (week 52) · Abnormal NCS	21 Participants	29 Participants
Change in Physical Examination Cardiovascular system (week 52) · Abnormal CS	4 Participants	2 Participants
Change in Physical Examination Nervous system (week -2) · Normal	390 Participants	376 Participants
Change in Physical Examination Nervous system (week -2) · Abnormal NCS	20 Participants	30 Participants
Change in Physical Examination Nervous system (week -2) · Abnormal CS	0 Participants	3 Participants
Change in Physical Examination Nervous system (week 52) · Normal	371 Participants	365 Participants
Change in Physical Examination Nervous system (week 52) · Abnormal NCS	13 Participants	17 Participants
Change in Physical Examination Nervous system (week 52) · Abnormal CS	1 Participants	1 Participants
Change in Physical Examination Gastrointestinal system (week -2) · Normal	387 Participants	384 Participants
Change in Physical Examination Gastrointestinal system (week -2) · Abnormal NCS	23 Participants	24 Participants
Change in Physical Examination Gastrointestinal system (week -2) · Abnormal CS	0 Participants	1 Participants
Change in Physical Examination Gastrointestinal system (week 52) · Normal	366 Participants	360 Participants
Change in Physical Examination Gastrointestinal system (week 52) · Abnormal NCS	18 Participants	22 Participants
Change in Physical Examination Gastrointestinal system (week 52) · Abnormal CS	1 Participants	0 Participants
Change in Physical Examination General appearance (week -2) · Normal	354 Participants	354 Participants
Change in Physical Examination General appearance (week -2) · Abnormal NCS	47 Participants	49 Participants
Change in Physical Examination General appearance (week -2) · Abnormal CS	9 Participants	6 Participants
Change in Physical Examination General appearance (week 52) · Normal	345 Participants	338 Participants
Change in Physical Examination General appearance (week 52) · Abnormal NCS	36 Participants	41 Participants
Change in Physical Examination General appearance (week 52) · Abnormal CS	4 Participants	4 Participants
Change in Physical Examination Head, throat, neck (week -2) · Normal	389 Participants	382 Participants
Change in Physical Examination Head, throat, neck (week -2) · Abnormal CS	3 Participants	1 Participants
Change in Physical Examination Head, throat, neck (week 52) · Normal	376 Participants	362 Participants
Change in Physical Examination Head, throat, neck (week 52) · Abnormal NCS	8 Participants	19 Participants
Change in Physical Examination Head, throat, neck (week 52) · Abnormal CS	1 Participants	2 Participants
Change in Physical Examination Lymph node palpation (week -2) · Normal	409 Participants	409 Participants
Change in Physical Examination Lymph node palpation (week -2) · Abnormal NCS	1 Participants	0 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	385 Participants	381 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 Musculoskeletal system (week -2) · Normal	389 Participants	384 Participants
Change in Physical Examination Musculoskeletal system (week -2) · Abnormal NCS	18 Participants	25 Participants
Change in Physical Examination Musculoskeletal system (week -2) · Abnormal CS	3 Participants	0 Participants
Change in Physical Examination Musculoskeletal system (week 52) · Normal	370 Participants	363 Participants
Change in Physical Examination Musculoskeletal system (week 52) · Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Respiratory system (week -2) · Normal	400 Participants	403 Participants
Change in Physical Examination Respiratory system (week -2) · Abnormal NCS	9 Participants	6 Participants
Change in Physical Examination Respiratory system (week -2) · Abnormal CS	1 Participants	0 Participants
Change in Physical Examination Respiratory system (week 52) · Normal	375 Participants	378 Participants
Change in Physical Examination Respiratory system (week 52) · Abnormal NCS	8 Participants	4 Participants
Change in Physical Examination Respiratory system (week 52) · Abnormal CS	2 Participants	0 Participants
Change in Physical Examination Skin (week -2) · Normal	357 Participants	354 Participants
Change in Physical Examination Skin (week -2) · Abnormal NCS	50 Participants	53 Participants
Change in Physical Examination Skin (week -2) · Abnormal CS	3 Participants	2 Participants
Change in Physical Examination Skin (week 52) · Normal	346 Participants	340 Participants
Change in Physical Examination Skin (week 52) · Abnormal NCS	37 Participants	42 Participants
Change in Physical Examination Skin (week 52) · Abnormal CS	2 Participants	1 Participants
Change in Physical Examination Thyroid gland (week -2) · Normal	399 Participants	389 Participants
Change in Physical Examination Thyroid gland (week -2) · Abnormal NCS	11 Participants	18 Participants
Change in Physical Examination Thyroid gland (week -2) · Abnormal CS	0 Participants	2 Participants
Change in Physical Examination Thyroid gland (week 52) · Normal	376 Participants	367 Participants
Change in Physical Examination Thyroid gland (week 52) · Abnormal NCS	9 Participants	16 Participants
Change in Physical Examination Thyroid gland (week 52) · Abnormal CS	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week -2, week 52

The eye examination findings (normal, abnormal NCS and abnormal CS) of the participants at baseline (week -2) and week 52 are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=410 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=409 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Eye Examination Left eye (week -2) · Normal	295 Participants	295 Participants
Change in Eye Examination Left eye (week -2) · Abnormal NCS	107 Participants	102 Participants
Change in Eye Examination Left eye (week -2) · Abnormal CS	7 Participants	10 Participants
Change in Eye Examination Left eye (week 52) · Normal	264 Participants	269 Participants
Change in Eye Examination Left eye (week 52) · Abnormal NCS	103 Participants	93 Participants
Change in Eye Examination Left eye (week 52) · Abnormal CS	8 Participants	10 Participants
Change in Eye Examination Right eye (week -2) · Normal	294 Participants	293 Participants
Change in Eye Examination Right eye (week -2) · Abnormal NCS	109 Participants	107 Participants
Change in Eye Examination Right eye (week -2) · Abnormal CS	6 Participants	9 Participants
Change in Eye Examination Right eye (week 52) · Normal	267 Participants	269 Participants
Change in Eye Examination Right eye (week 52) · Abnormal NCS	96 Participants	93 Participants
Change in Eye Examination Right eye (week 52) · Abnormal CS	11 Participants	11 Participants

SECONDARY outcome

Timeframe: Weeks 0-57

Population: Overall number of participants analyzed = number of participants with available data.

This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide binding antibodies anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=403 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)	2 Participants	—

SECONDARY outcome

Timeframe: Weeks 0-57

Population: Overall number of participants analyzed = number of participants with available data.

This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=403 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)	0 Participants	—

SECONDARY outcome

Timeframe: Weeks 0-57

Population: Overall number of participants analyzed = number of participants with available data.

This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=403 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no)	0 Participants	—

SECONDARY outcome

Timeframe: Weeks 0-57

Population: Overall number of participants analyzed = number of participants with available data.

This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies cross reacting with native GLP-1 anytime during post-baseline visits (week 0 to week 57) are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=403 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)	0 Participants	—

SECONDARY outcome

Timeframe: Weeks 0-57

Population: Overall number of participants analysed = participants who were found positive for anti-semaglutide antibodies.

This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. It is based on the data from participants who were measured with anti-semaglutide antibodies anytime during post-baseline visits (week 0 to week 57). Results are presented as percentage of bound radioactivity-labelled semaglutide /total added radioactivity-labelled semaglutide (%B/T). The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=2 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Anti-semaglutide Binding Antibody Levels Week 4	2.75 %B/T Standard Deviation 0.00	—
Anti-semaglutide Binding Antibody Levels Week 8	2.17 %B/T Standard Deviation 0.00	—

SECONDARY outcome

Timeframe: Weeks 0-57

Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.

Treatment-emergent hypoglycaemia is an episode with onset in the on-treatment observation period (the time period where participants are considered treated with trial product) and was assessed up to approximately 57 weeks (52-week treatment period plus the 5-week follow-up 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 data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=410 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=409 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes	10 Episodes	9 Episodes

SECONDARY outcome

Timeframe: Weeks 0-57

Population: Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.

Number of participants with treatment-emergent severe or BG-confirmed symptomatic hypoglycaemic episodes was recorded during week 0-57. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=410 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=409 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)	7 Participants	8 Participants

SECONDARY outcome

Timeframe: Weeks 0-52

Semaglutide plasma concentrations were measured after 25 minutes post-dose at week 4, 26 and 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Semaglutide Plasma Concentrations for Population PK Analyses Week 4	3.5 Nanomoles per liter (nmol/L) Geometric Coefficient of Variation 84.5	—
Semaglutide Plasma Concentrations for Population PK Analyses Week 26	15.6 Nanomoles per liter (nmol/L) Geometric Coefficient of Variation 112.4	—
Semaglutide Plasma Concentrations for Population PK Analyses Week 52	14.4 Nanomoles per liter (nmol/L) Geometric Coefficient of Variation 136.6	—

SECONDARY outcome

Timeframe: Weeks 0-52

This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Sodium N-\[8-(2-hydroxybenzoyl) amino\]caprylate (SNAC) plasma concentrations were measured after 25 and 40 minutes post-dose at week 4, 26 and 52. Results are based on the data from the on-treatment observation period. On-treatment observation period: the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
SNAC Plasma Concentrations Week 4: 25 minutes post-dose	559 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 224.6	—
SNAC Plasma Concentrations Week 4: 40 minutes post-dose	375 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 210.4	—
SNAC Plasma Concentrations Week 26: 25 minutes post-dose	474 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 272.7	—
SNAC Plasma Concentrations Week 26: 40 minutes post-dose	373 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 200.6	—
SNAC Plasma Concentrations Week 52: 25 minutes post-dose	448 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 377.5	—
SNAC Plasma Concentrations Week 52: 40 minutes post-dose	301 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 290.2	—

SECONDARY outcome

Timeframe: Week 0, week 26, week 52

SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (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. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 26 and 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 26: Physical Functioning	0.87 Score on a scale Standard Deviation 7.35	0.99 Score on a scale Standard Deviation 7.11
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 52: Physical Functioning	0.57 Score on a scale Standard Deviation 6.79	0.84 Score on a scale Standard Deviation 7.32
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 26: Role functioning	0.07 Score on a scale Standard Deviation 6.82	0.56 Score on a scale Standard Deviation 8.36
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 52: Role functioning	-0.61 Score on a scale Standard Deviation 6.78	0.52 Score on a scale Standard Deviation 7.93
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 26: Bodily pain	-0.32 Score on a scale Standard Deviation 9.77	1.04 Score on a scale Standard Deviation 9.53
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 52: Bodily pain	-0.33 Score on a scale Standard Deviation 10.07	1.20 Score on a scale Standard Deviation 9.54
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 26: General health	2.26 Score on a scale Standard Deviation 6.59	1.36 Score on a scale Standard Deviation 6.56
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 52: General health	2.47 Score on a scale Standard Deviation 7.35	1.86 Score on a scale Standard Deviation 7.66
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 26: Vitality	0.66 Score on a scale Standard Deviation 7.58	0.49 Score on a scale Standard Deviation 7.60
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 52: Vitality	0.83 Score on a scale Standard Deviation 7.72	1.15 Score on a scale Standard Deviation 7.48
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 26: Social functioning	0.50 Score on a scale Standard Deviation 7.28	-0.54 Score on a scale Standard Deviation 8.15
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 52: Social functioning	-0.18 Score on a scale Standard Deviation 8.35	-0.54 Score on a scale Standard Deviation 8.63
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 26: Role emotional	0.67 Score on a scale Standard Deviation 9.47	0.53 Score on a scale Standard Deviation 9.49
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 52: Role emotional	0.30 Score on a scale Standard Deviation 9.63	0.42 Score on a scale Standard Deviation 9.93
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 26: Mental health	0.94 Score on a scale Standard Deviation 8.06	-0.03 Score on a scale Standard Deviation 8.70
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 52: Mental health	0.29 Score on a scale Standard Deviation 8.71	-0.03 Score on a scale Standard Deviation 9.21
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 26: PCS	0.53 Score on a scale Standard Deviation 6.36	1.21 Score on a scale Standard Deviation 6.39
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 52: PCS	0.44 Score on a scale Standard Deviation 6.26	1.36 Score on a scale Standard Deviation 6.50
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 26: MCS	0.83 Score on a scale Standard Deviation 7.54	-0.23 Score on a scale Standard Deviation 8.40
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) Week 52: MCS	0.35 Score on a scale Standard Deviation 8.36	-0.09 Score on a scale Standard Deviation 8.64

SECONDARY outcome

Timeframe: Week 0, week 26, week 52

Change from baseline (week 0) in Control of Eating Questionnaire (CoEQ) was evaluated at weeks 26 and 52. The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control' (items 9-12, 19), 'positive mood' (items 5-8), 'craving for savoury' (items 4, 16-18) and 'craving for sweet' (items 3, 13-15). 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 data from the in-trial observation period.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 14 mg n=411 Participants Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=410 Participants Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: Positive Mood	0.08 Score on a scale Standard Deviation 1.52	0.19 Score on a scale Standard Deviation 1.62
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: Positive Mood	0.15 Score on a scale Standard Deviation 1.75	0.17 Score on a scale Standard Deviation 1.64
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: Craving control	0.46 Score on a scale Standard Deviation 2.60	0.21 Score on a scale Standard Deviation 2.26
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: Craving control	0.44 Score on a scale Standard Deviation 2.54	0.18 Score on a scale Standard Deviation 2.38
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: Craving for Savoury	-0.68 Score on a scale Standard Deviation 2.13	-0.54 Score on a scale Standard Deviation 2.05
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: Craving for Savoury	-0.66 Score on a scale Standard Deviation 2.16	-0.44 Score on a scale Standard Deviation 2.14
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: Craving for Sweet	-0.25 Score on a scale Standard Deviation 2.15	-0.21 Score on a scale Standard Deviation 2.04
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: Craving for Sweet	-0.21 Score on a scale Standard Deviation 2.23	-0.17 Score on a scale Standard Deviation 2.13
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 1.Feeling of hunger	-0.80 Score on a scale Standard Deviation 2.69	-0.09 Score on a scale Standard Deviation 2.59
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 1.Feeling of hunger	-0.60 Score on a scale Standard Deviation 2.82	0.07 Score on a scale Standard Deviation 2.56
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 2.Feeling of fullness	0.40 Score on a scale Standard Deviation 2.65	0.29 Score on a scale Standard Deviation 2.63
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 2.Feeling of fullness	0.35 Score on a scale Standard Deviation 2.75	0.06 Score on a scale Standard Deviation 2.67
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 3.Desire to eat sweet foods	-0.35 Score on a scale Standard Deviation 3.04	-0.22 Score on a scale Standard Deviation 2.95
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 3.Desire to eat sweet foods	-0.36 Score on a scale Standard Deviation 3.23	-0.18 Score on a scale Standard Deviation 2.85
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 4.Desire to eat savoury foods	-0.82 Score on a scale Standard Deviation 2.99	-0.56 Score on a scale Standard Deviation 3.09
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 4.Desire to eat savoury foods	-0.82 Score on a scale Standard Deviation 3.15	-0.57 Score on a scale Standard Deviation 2.93
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 5.Feeling of happiness	0.00 Score on a scale Standard Deviation 2.24	0.21 Score on a scale Standard Deviation 2.31
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 5.Feeling of happiness	0.13 Score on a scale Standard Deviation 2.61	0.21 Score on a scale Standard Deviation 2.36
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 6.Feeling of anxiousness	-0.21 Score on a scale Standard Deviation 2.92	-0.31 Score on a scale Standard Deviation 3.22
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 6.Feeling of anxiousness	-0.19 Score on a scale Standard Deviation 3.03	-0.21 Score on a scale Standard Deviation 3.02
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 7.Feeling of alertness	0.01 Score on a scale Standard Deviation 2.68	0.02 Score on a scale Standard Deviation 2.57
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 7.Feeling of alertness	0.07 Score on a scale Standard Deviation 2.73	0.08 Score on a scale Standard Deviation 2.63
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 8.Feeling of contentment	0.08 Score on a scale Standard Deviation 2.37	0.22 Score on a scale Standard Deviation 2.42
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 8.Feeling of contentment	0.23 Score on a scale Standard Deviation 2.54	0.17 Score on a scale Standard Deviation 2.30
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 9.Food cravings during 7 days	-0.43 Score on a scale Standard Deviation 3.25	-0.03 Score on a scale Standard Deviation 3.03
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 9.Food cravings during 7 days	-0.42 Score on a scale Standard Deviation 3.23	-0.17 Score on a scale Standard Deviation 2.98
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 10.Strength of food cravings	-0.27 Score on a scale Standard Deviation 3.11	-0.18 Score on a scale Standard Deviation 2.97
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 10.Strength of food cravings	-0.32 Score on a scale Standard Deviation 3.13	-0.14 Score on a scale Standard Deviation 3.01
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 11.Difficulty to resist food cravings	-0.47 Score on a scale Standard Deviation 3.41	-0.35 Score on a scale Standard Deviation 3.18
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 11.Difficulty to resist food cravings	-0.33 Score on a scale Standard Deviation 3.26	-0.30 Score on a scale Standard Deviation 3.24
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 12.Eating in response to food cravings	-0.19 Score on a scale Standard Deviation 2.94	-0.12 Score on a scale Standard Deviation 2.75
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 12.Eating in response to food cravings	-0.17 Score on a scale Standard Deviation 2.97	-0.01 Score on a scale Standard Deviation 2.93
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 13.Cravings for chocolate	-0.10 Score on a scale Standard Deviation 3.03	-0.26 Score on a scale Standard Deviation 3.02
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 13.Cravings for chocolate	0.08 Score on a scale Standard Deviation 3.13	-0.12 Score on a scale Standard Deviation 3.00
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 14.Cravings for other sweet foods	-0.39 Score on a scale Standard Deviation 2.91	-0.36 Score on a scale Standard Deviation 2.94
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 14.Cravings for other sweet foods	-0.33 Score on a scale Standard Deviation 2.90	-0.24 Score on a scale Standard Deviation 3.13
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 15.Cravings for fruit or fruit juice	-0.15 Score on a scale Standard Deviation 3.29	0.01 Score on a scale Standard Deviation 3.11
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 15.Cravings for fruit or fruit juice	-0.22 Score on a scale Standard Deviation 3.31	-0.15 Score on a scale Standard Deviation 3.14
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 16.Cravings for dairy foods	-0.48 Score on a scale Standard Deviation 3.05	-0.43 Score on a scale Standard Deviation 2.88
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 16.Cravings for dairy foods	-0.42 Score on a scale Standard Deviation 3.11	-0.16 Score on a scale Standard Deviation 2.92
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 17.Cravings for starchy foods	-0.81 Score on a scale Standard Deviation 2.99	-0.59 Score on a scale Standard Deviation 2.64
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 17.Cravings for starchy foods	-0.78 Score on a scale Standard Deviation 3.04	-0.51 Score on a scale Standard Deviation 2.99
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 18.Cravings for savoury foods	-0.61 Score on a scale Standard Deviation 3.02	-0.56 Score on a scale Standard Deviation 2.93
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 18.Cravings for savoury foods	-0.60 Score on a scale Standard Deviation 2.92	-0.50 Score on a scale Standard Deviation 3.09
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 26: 19.Difficulty to control eating general	-0.90 Score on a scale Standard Deviation 3.09	-0.36 Score on a scale Standard Deviation 2.79
Change in CoEQ: Scores From the 4 Domains and the 19 Items Week 52: 19.Difficulty to control eating general	-0.97 Score on a scale Standard Deviation 3.01	-0.27 Score on a scale Standard Deviation 2.82

Adverse Events

Oral Semaglutide 14 mg

Serious events: 27 serious events

Other events: 128 other events

Deaths: 0 deaths

Empagliflozin 25 mg

Serious events: 37 serious events

Other events: 44 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Oral Semaglutide 14 mg n=410 participants at risk Participants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).	Empagliflozin 25 mg n=409 participants at risk Participants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.
Metabolism and nutrition disorders Decreased appetite	5.1% 21/410 • Number of events 21 • Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product. Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	0.49% 2/409 • Number of events 2 • Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product. Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Gastrointestinal disorders Diarrhoea	9.3% 38/410 • Number of events 48 • Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product. Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	3.2% 13/409 • Number of events 17 • Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product. Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Infections and infestations Influenza	2.0% 8/410 • Number of events 8 • Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product. Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	5.1% 21/409 • Number of events 23 • Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product. Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Gastrointestinal disorders Nausea	19.8% 81/410 • Number of events 106 • Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product. Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	2.4% 10/409 • Number of events 12 • Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product. Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Gastrointestinal disorders Vomiting	7.3% 30/410 • Number of events 40 • Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product. Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	1.7% 7/409 • Number of events 7 • Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product. Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

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.
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