Trial Outcomes & Findings for LIRA-ADD2SGLT2i - Liraglutide Versus Placebo as add-on to SGLT2 Inhibitors. (NCT NCT02964247)

NCT ID: NCT02964247

Last Updated: 2020-11-17

Results Overview

Change from baseline (week 0) to week 26 in glycosylated haemoglobin was evaluated for 2 different observation period 'in-trial' observation period and 'on-treatment without rescue medication" observation period. The 'in-trial' observation period represents the time-period where subjects were considered to be in the trial, regardless of whether or not the subjects had initiated rescue medication or prematurely discontinued trial product. The 'on-treatment' observation period is the part of the in-trial observation period during which subjects were treated with the trial product, that is the time from the first dose to the last dose of trial product. The 'on-treatment without rescue medication' observation period is a part of 'on-treatment' observation period during which subjects were considered treated with trial product and had not initiated any rescue medications.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 303 participants
• Primary outcome timeframe: Week 0, Week 26
• Results posted on: 2020-11-17

Participant Flow

The trial was conducted at 74 sites in 7 countries. All the sites have screened and randomised subjects. Brazil: 3 sites, India: 7 sites, Israel: 6 sites, Mexico: 2 sites, Russian Federation: 3 sites, United Arab Emirates: 5 sites, United States: 48 sites screened and randomised subjects.

Participant milestones

Measure	Liraglutide Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Overall Study STARTED	203	100
Overall Study Exposed to Trial Product	202	100
Overall Study COMPLETED	200	98
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Measure	Liraglutide Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	1	2

Baseline Characteristics

LIRA-ADD2SGLT2i - Liraglutide Versus Placebo as add-on to SGLT2 Inhibitors.

Baseline characteristics by cohort

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Total n=303 Participants Total of all reporting groups
Age, Continuous	54.72 Years STANDARD_DEVIATION 10.08 • n=5 Participants	56.03 Years STANDARD_DEVIATION 9.89 • n=7 Participants	55.15 Years STANDARD_DEVIATION 10.02 • n=5 Participants
Sex: Female, Male Female	78 Participants n=5 Participants	42 Participants n=7 Participants	120 Participants n=5 Participants
Sex: Female, Male Male	125 Participants n=5 Participants	58 Participants n=7 Participants	183 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	59 Participants n=5 Participants	35 Participants n=7 Participants	94 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	144 Participants n=5 Participants	65 Participants n=7 Participants	209 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 American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	38 Participants n=5 Participants	15 Participants n=7 Participants	53 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	12 Participants n=5 Participants	5 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized White	131 Participants n=5 Participants	59 Participants n=7 Participants	190 Participants n=5 Participants
Race/Ethnicity, Customized Other	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Change from baseline (week 0) to week 26 in glycosylated haemoglobin was evaluated for 2 different observation period 'in-trial' observation period and 'on-treatment without rescue medication" observation period. The 'in-trial' observation period represents the time-period where subjects were considered to be in the trial, regardless of whether or not the subjects had initiated rescue medication or prematurely discontinued trial product. The 'on-treatment' observation period is the part of the in-trial observation period during which subjects were treated with the trial product, that is the time from the first dose to the last dose of trial product. The 'on-treatment without rescue medication' observation period is a part of 'on-treatment' observation period during which subjects were considered treated with trial product and had not initiated any rescue medications.

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in HbA1c in-trial obs. period	-1.00 Percentage of HbA1c Standard Deviation 0.86	-0.32 Percentage of HbA1c Standard Deviation 0.83
Change in HbA1c on-treatment without rescue medication obs. period	-1.05 Percentage of HbA1c Standard Deviation 0.85	-0.35 Percentage of HbA1c Standard Deviation 0.80

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Change from baseline (week 0) to week 26 in body weight was evaluated for 2 different observation period 'in-trial' observation period and 'on-treatment without rescue medication" observation period. The 'in-trial' observation period represents the time-period where subjects were considered to be in the trial, regardless of whether or not the subjects had initiated rescue medication or prematurely discontinued trial product. The 'on-treatment' observation period is the part of the in-trial observation period during which subjects were treated with the trial product, that is the time from the first dose to the last dose of trial product. The 'on-treatment without rescue medication' observation period is a part of 'on-treatment' observation period during which subjects were considered treated with trial product and had not initiated any rescue medications.

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Body Weight in-trial obs. period	-2.84 Kg Standard Deviation 3.83	-2.02 Kg Standard Deviation 3.32
Change in Body Weight on-treatment without rescue medication obs. period	-2.89 Kg Standard Deviation 3.81	-2.09 Kg Standard Deviation 2.96

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Change from baseline (week 0) to week 26 in fasting plasma glucose ('in-trial' observation period)

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Fasting Plasma Glucose	-27.00 milligram/dL Standard Deviation 35.01	-11.97 milligram/dL Standard Deviation 45.20

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Percentage of subjects who achieve HbA1c below 7.0% (53 mmol/mol), American Diabetes Association target, after 26 weeks ('in-trial' observation period)

Outcome measures

Measure	Liraglutide n=195 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=95 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target Yes	51.79 Percentage of Participants	23.16 Percentage of Participants
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target No	48.21 Percentage of Participants	76.84 Percentage of Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Percentage of subjects who achieve HbA1c below or equal to 6.5% (48 mmol/mol), American Association of Clinical Endocrinologists target, after 26 weeks ('in-trial' observation period)

Outcome measures

Measure	Liraglutide n=195 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=95 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target Yes	34.36 Percentage of Participants	9.47 Percentage of Participants
Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target No	65.64 Percentage of Participants	90.53 Percentage of Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Percentage of subjects who achieve HbA1c below 7.0% (53 mmol/mol) without severe or blood glucose confirmed symptomatic hypoglycaemia episodes and no weight gain, after 26 weeks ('in-trial' observation period)

Outcome measures

Measure	Liraglutide n=195 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=94 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain. Yes	47.69 Percentage of Participants	19.15 Percentage of Participants
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain. No	52.31 Percentage of Participants	80.85 Percentage of Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Percentage of subjects who achieve HbA1c reduction above or equal to 1% (11mmol/mol) and weight loss above or equal to 3%, after 26 weeks ('in-trial' observation period)

Outcome measures

Measure	Liraglutide n=195 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=94 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and Weight Loss Above or Equal to 3%. Yes	29.74 Percentage of Participants	7.45 Percentage of Participants
Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and Weight Loss Above or Equal to 3%. No	70.26 Percentage of Participants	92.55 Percentage of Participants

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Change in self-measured plasma glucose 7-point profile - mean 7-point profile after 26 weeks. Subjects were instructed to measure their plasma glucose at following 7 timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime. Mean of the 7-point profile was calculated ('in-trial' observation period).

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Self-measured Plasma Glucose 7-point Profile - Mean 7-point Profile	-33.93 milligram/dL Standard Deviation 37.17	-18.85 milligram/dL Standard Deviation 40.81

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Subjects were instructed to measure their plasma glucose at following 7 timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime. The mean increment over all meals was derived as the mean of all available meal increments ('in-trial' observation period)

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Self-measured Plasma Glucose 7-point Profile - Mean Post Prandial Increments (Over All Meals)	-11.06 milligram/dL Standard Deviation 41.29	-4.44 milligram/dL Standard Deviation 44.77

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Observed mean change from baseline (week 0) to week 26 in body mass index (BMI). BMI was calculated based on body weight and height ('in-trial' observation period)

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Body Mass Index (BMI)	-1.02 kg/m^2 Standard Deviation 1.40	-0.72 kg/m^2 Standard Deviation 1.20

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Percentage of subjects who achieve HbA1c below 7.0% (53 mmol/mol) and no weight gain, after 26 week ('in-trial' observation period).

Outcome measures

Measure	Liraglutide n=195 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=94 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain Yes	47.69 Percentage of Participants	19.15 Percentage of Participants
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain No	52.31 Percentage of Participants	80.85 Percentage of Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Percentage of subjects who achieve HbA1c below 7.0% (53 mmol/mol), no weight gain and systolic blood pressure below 140 mmHg, after 26 weeks ('in-trial' observation period)

Outcome measures

Measure	Liraglutide n=195 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=94 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), no Weight Gain and Systolic Blood Pressure Below 140 mmHg. Yes	42.05 Percentage of Participants	18.09 Percentage of Participants
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), no Weight Gain and Systolic Blood Pressure Below 140 mmHg. No	57.95 Percentage of Participants	81.91 Percentage of Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Percentage of subjects who achieve HbA1c reduction above or equal to 1% (11mmol/mol), after 26 weeks ('in-trial' observation period)

Outcome measures

Measure	Liraglutide n=195 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=95 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) Yes	52.31 Percentage of Participants	16.84 Percentage of Participants
Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) No	47.69 Percentage of Participants	83.16 Percentage of Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Percentage of subjects who achieve HbA1c reduction above or equal to 1% (11mmol/mol) and no weight gain, after 26 weeks.

Outcome measures

Measure	Liraglutide n=195 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=94 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and no Weight Gain Yes	45.13 Percentage of Participants	14.89 Percentage of Participants
Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and no Weight Gain No	54.87 Percentage of Participants	85.11 Percentage of Participants

SECONDARY outcome

Timeframe: Week 0 - 26 + 7 days

Population: Safety analysis set (SAS) includes all subjects exposed to at least one dose of trial product. Subjects in the SAS contribute to the evaluation based on the trial product received for the period they were on-treatment, referred to as contributing to the evaluation 'as treated'. 'Number Analyzed' = subjects with available data.

The on-treatment summary of adverse events includes treatment-emergent events with onset on or after the first day of exposure to randomised treatment and no later than the minimum of the date of the follow-up visit or the last day of randomised treatment + 7 days or the date of last subject-investigator contact.

Outcome measures

Measure	Liraglutide n=202 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Number of Treatment Emergent Adverse Events	426 Events	106 Events

SECONDARY outcome

Timeframe: Week 0 - 26

Population: Safety analysis set (SAS) includes all subjects exposed to at least one dose of trial product. Subjects in the SAS contribute to the evaluation based on the trial product received for the period they were on-treatment, referred to as contributing to the evaluation 'as treated'. 'Number Analyzed' = subjects with available data.

Treatment emergent hypoglycaemic episode is defined episode with onset on or after the first day of exposure to randomised treatment and no later than the minimum of the date of the follow-up visit or the last day of randomised treatment + 1 days or the date of last subject-investigator contact. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to American Diabetes Association's (ADA) classification or blood glucose confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Severe hypoglycaemia according to the ADA definition: an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions.

Outcome measures

Measure	Liraglutide n=202 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes	0 Episodes	3 Episodes

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Fasting total cholesterol measured in mg/dL. Observed mean change in fasting total cholesterol from baseline (week 0) to week 26 is presented as ratio to baseline value.

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Fasting Blood Lipids - Total Cholesterol	0.95 Ratio Geometric Coefficient of Variation 45.1	0.99 Ratio Geometric Coefficient of Variation 42.3

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Low density lipoprotein (LDL) cholesterol measured in mg/dL. Observed mean change in fasting low density lipoprotein cholesterol from baseline (week 0) to week 26 is presented as ratio to baseline value.

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Fasting Blood Lipids - Low Density Lipoprotein (LDL) Cholesterol	0.97 Ratio Geometric Coefficient of Variation 58.6	1.01 Ratio Geometric Coefficient of Variation 54.1

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

High density lipoprotein (HDL) cholesterol measured in mg/dL. Observed mean change in fasting high density lipoprotein cholesterol from baseline (week 0) to week 26 is presented as ratio to baseline value.

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Fasting Blood Lipids - High Density Lipoprotein (HDL) Cholesterol	1.05 Ratio Geometric Coefficient of Variation 41.4	1.01 Ratio Geometric Coefficient of Variation 39.7

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Very low density lipoprotein (VLDL) cholesterol measured in mg/dL. Observed mean change in fasting very low density lipoprotein cholesterol from baseline (week 0) to week 26 is presented as ratio to baseline value.

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Fasting Blood Lipids - Very Low Density Lipoprotein (VLDL) Cholesterol	0.83 Ratio Geometric Coefficient of Variation 69.0	0.94 Ratio Geometric Coefficient of Variation 64.5

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Fasting triglycerides measured in mg/dL. Observed mean change in fasting triglycerides from baseline (week 0) to week 26 is presented as ratio to baseline value.

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Fasting Blood Lipids-triglycerides	0.81 Ratio Geometric Coefficient of Variation 71.5	0.93 Ratio Geometric Coefficient of Variation 70.0

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Free fatty acids measured in mg/dL. Observed mean change in fasting free fatty acids from baseline (week 0) to week 26 is presented as ratio to baseline value.

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Fasting Blood Lipids- Free Fatty Acids (FFA)	0.80 Ratio Geometric Coefficient of Variation 86.6	0.86 Ratio Geometric Coefficient of Variation 92.0

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Change from baseline (week 0) to week 26 in waist circumference ('in-trial' observation period).

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Waist Circumference	-4.28 cm Standard Deviation 11.19	-1.77 cm Standard Deviation 4.42

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Change from baseline (week 0) in systolic blood pressure after 26 weeks ('in-trial' observation period).

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Systolic Blood Pressure	-1.95 mmHg Standard Deviation 13.42	-3.35 mmHg Standard Deviation 12.36

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Change from baseline (week 0) in diastolic blood pressure after 26 weeks ('in-trial' observation period).

Outcome measures

Measure	Liraglutide n=203 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Change in Diastolic Blood Pressure	-0.72 mmHg Standard Deviation 8.04	-1.12 mmHg Standard Deviation 8.55

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.

Percentage of subjects who achieve HbA1c reduction above or equal to 1% (11mmol/mol) and weight loss above or equal to 3%, after 26 weeks ('in-trial' observation period).

Outcome measures

Measure	Liraglutide n=196 Participants Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=97 Participants Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Subjects Who Achieve Weight Loss by 3% or More Yes	46.43 Percentage of participants	41.24 Percentage of participants
Subjects Who Achieve Weight Loss by 3% or More No	53.57 Percentage of participants	58.76 Percentage of participants

Adverse Events

Liraglutide

Serious events: 5 serious events

Other events: 87 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Liraglutide n=202 participants at risk Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 participants at risk Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Renal and urinary disorders Acute kidney injury	0.00% 0/202 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	1.0% 1/100 • Number of events 1 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Cardiac disorders Angina unstable	0.50% 1/202 • Number of events 1 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	0.00% 0/100 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Cardiac disorders Cardiac failure congestive	0.50% 1/202 • Number of events 1 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	0.00% 0/100 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Hepatobiliary disorders Cholecystitis	0.50% 1/202 • Number of events 1 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	0.00% 0/100 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Cardiac disorders Congestive cardiomyopathy	0.50% 1/202 • Number of events 1 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	0.00% 0/100 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Eye disorders Eyelid cyst	0.50% 1/202 • Number of events 1 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	0.00% 0/100 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Gastrointestinal disorders Haemorrhoids	0.50% 1/202 • Number of events 1 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	0.00% 0/100 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.50% 1/202 • Number of events 1 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	0.00% 0/100 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Renal and urinary disorders Ureterolithiasis	0.00% 0/202 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	1.0% 1/100 • Number of events 1 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.

Other adverse events

Measure	Liraglutide n=202 participants at risk Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.	Placebo n=100 participants at risk Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.
Gastrointestinal disorders Constipation	8.9% 18/202 • Number of events 19 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	0.00% 0/100 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Metabolism and nutrition disorders Decreased appetite	9.4% 19/202 • Number of events 19 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	0.00% 0/100 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Gastrointestinal disorders Diarrhoea	9.4% 19/202 • Number of events 24 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	3.0% 3/100 • Number of events 3 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Gastrointestinal disorders Nausea	26.2% 53/202 • Number of events 61 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	6.0% 6/100 • Number of events 8 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.
Gastrointestinal disorders Vomiting	8.4% 17/202 • Number of events 20 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.	2.0% 2/100 • Number of events 2 • Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Safety analysis set includes all subjects exposed to at least one dose of trial product.

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: clinicaltrials@novonordisk.com

Results disclosure agreements

• Principal investigator is a sponsor employee At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
• Publication restrictions are in place

Restriction type: OTHER