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

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02964247
• Collaborator: (none)
• Enrollment: 303
• Locations: 82
• Arms: 2
• Actual Duration (Months): 14.2
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The trial is conducted in Asia, Europe, North America and South America. The aim of the study is to compare the effect of liraglutide 1.8 mg/day versus placebo as add-on to an SGLT2 inhibitor with or without metformin on glycaemic control in subjects with type 2 diabetes mellitus.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: liraglutide; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 303 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: LIRA-ADD2SGLT2i - Liraglutide Versus Placebo as add-on to SGLT2 Inhibitors
• Actual Study Start Date: Mar 3, 2017
• Actual Primary Completion Date: May 4, 2018
• Actual Study Completion Date: May 8, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: liraglutide + SGLT2i ± metformin	Drug: liraglutide; Liraglutide given s.c. once daily, gradually titrated to 1.8 mg/day as an add-on to the subject's stable pre-trial SGLT2 inhibitor ± metformin for 26 weeks
Placebo Comparator: liraglutide placebo + SGLT2i ± metformin	Drug: placebo; Liraglutide placebo given s.c. once daily, gradually titrated to 1.8 mg/day as an add-on to the subject's stable pre-trial SGLT2 inhibitor ± metformin for 26 weeks

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c [Week 0, Week 26]

   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.

Secondary Outcome Measures

1. Change in Body Weight [Week 0, Week 26]

   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.

2. Change in Fasting Plasma Glucose [Week 0, Week 26]

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

3. Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target [Week 26]

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

4. Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target [Week 26]

   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)

5. Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain. [Week 26]

   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)

6. Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and Weight Loss Above or Equal to 3%. [Week 26]

   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)

7. Change in Self-measured Plasma Glucose 7-point Profile - Mean 7-point Profile [Week 0, Week 26]

   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).

8. Change in Self-measured Plasma Glucose 7-point Profile - Mean Post Prandial Increments (Over All Meals) [Week 0, Week 26]

   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)

9. Change in Body Mass Index (BMI) [Week 0, Week 26]

   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)

10. Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain [Week 26]

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

11. Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), no Weight Gain and Systolic Blood Pressure Below 140 mmHg. [Week 26]

    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)

12. Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) [Week 26]

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

13. Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and no Weight Gain [Week 26]

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

14. Number of Treatment Emergent Adverse Events [Week 0 - 26 + 7 days]

    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.

15. Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes [Week 0 - 26]

    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.

16. Change in Fasting Blood Lipids - Total Cholesterol [Week 0, Week 26]

    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.

17. Change in Fasting Blood Lipids - Low Density Lipoprotein (LDL) Cholesterol [Week 0, Week 26]

    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.

18. Change in Fasting Blood Lipids - High Density Lipoprotein (HDL) Cholesterol [Week 0, Week 26]

    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.

19. Change in Fasting Blood Lipids - Very Low Density Lipoprotein (VLDL) Cholesterol [Week 0, Week 26]

    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.

20. Change in Fasting Blood Lipids-triglycerides [Week 0, Week 26]

    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.

21. Change in Fasting Blood Lipids- Free Fatty Acids (FFA) [Week 0, Week 26]

    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.

22. Change in Waist Circumference [Week 0, Week 26]

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

23. Change in Systolic Blood Pressure [Week 0, Week 26]

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

24. Change in Diastolic Blood Pressure [Week 0, Week 26]

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

25. Subjects Who Achieve Weight Loss by 3% or More [Week 26]

    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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.

• Male or female, age 18 years or older at the time of signing informed consent.

• Diagnosed with type 2 diabetes mellitus.

• HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive).

• Stable dose of an SGLT-2 inhibitor as monotherapy or in combination (including fixed-dose drug combination) with a stable dose of metformin (1500 mg or more, or maximum tolerated dose) for at least 90 days prior to the day of screening. All medications in compliance with current local label.

• Body mass index of 20 kg/m^2 or above.

Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice).

• History of diabetic ketoacidosis while being treated with SGLT2 inhibitors.

• Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of less than 60 mL/min/1.73m^2 as defined by Kidney Disease Improving Global Outcomes (KDIGO) classification using isotope dilution mass spectrometry (IDMS) for serum creatinine measured at screening.

• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days during the 90 days prior to screening is allowed.

• Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative.

• History or presence of pancreatitis (acute or chronic).

• Impaired liver function, defined as ALT 2.5 or more times upper normal limit at screening.

• Subjects presently classified as being in New York Heart Association (NYHA) Class IV.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35294
2	Novo Nordisk Investigational Site	Montgomery	Alabama	United States	36109
3	Novo Nordisk Investigational Site	Tucson	Arizona	United States	85741
4	Novo Nordisk Investigational Site	Lancaster	California	United States	93534
5	Novo Nordisk Investigational Site	Northridge	California	United States	91325
6	Novo Nordisk Investigational Site	Sacramento	California	United States	95821
7	Novo Nordisk Investigational Site	San Diego	California	United States	92111
8	Novo Nordisk Investigational Site	San Ramon	California	United States	94583
9	Novo Nordisk Investigational Site	Vista	California	United States	92083
10	Novo Nordisk Investigational Site	Gainesville	Florida	United States	32653
11	Novo Nordisk Investigational Site	Hollywood	Florida	United States	33024
12	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32216
13	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32256
14	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32258
15	Novo Nordisk Investigational Site	Maitland	Florida	United States	32751
16	Novo Nordisk Investigational Site	Miami Lakes	Florida	United States	33016
17	Novo Nordisk Investigational Site	Miami	Florida	United States	33165
18	Novo Nordisk Investigational Site	Miami	Florida	United States	33176
19	Novo Nordisk Investigational Site	Tampa	Florida	United States	33606
20	Novo Nordisk Investigational Site	Lawrenceville	Georgia	United States	30046
21	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
22	Novo Nordisk Investigational Site	Statesboro	Georgia	United States	30461
23	Novo Nordisk Investigational Site	Blackfoot	Idaho	United States	83221
24	Novo Nordisk Investigational Site	Evansville	Indiana	United States	47714
25	Novo Nordisk Investigational Site	Topeka	Kansas	United States	66606
26	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
27	Novo Nordisk Investigational Site	New Orleans	Louisiana	United States	70115
28	Novo Nordisk Investigational Site	Kalamazoo	Michigan	United States	49009
29	Novo Nordisk Investigational Site	Rochester	Michigan	United States	48307
30	Novo Nordisk Investigational Site	Billings	Montana	United States	59101
31	Novo Nordisk Investigational Site	Henderson	Nevada	United States	89052-2649
32	Novo Nordisk Investigational Site	Albany	New York	United States	12203
33	Novo Nordisk Investigational Site	West Seneca	New York	United States	14224
34	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28210
35	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28226
36	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28277
37	Novo Nordisk Investigational Site	Kinston	North Carolina	United States	28501
38	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
39	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45245
40	Novo Nordisk Investigational Site	Columbus	Ohio	United States	43212
41	Novo Nordisk Investigational Site	McMurray	Pennsylvania	United States	15317
42	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania	United States	15243
43	Novo Nordisk Investigational Site	Moncks Corner	South Carolina	United States	29461
44	Novo Nordisk Investigational Site	Mount Pleasant	South Carolina	United States	29464
45	Novo Nordisk Investigational Site	Myrtle Beach	South Carolina	United States	29572
46	Novo Nordisk Investigational Site	Spartanburg	South Carolina	United States	29303
47	Novo Nordisk Investigational Site	Memphis	Tennessee	United States	38119
48	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37203
49	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
50	Novo Nordisk Investigational Site	Edinburg	Texas	United States	78539
51	Novo Nordisk Investigational Site	Houston	Texas	United States	77024
52	Novo Nordisk Investigational Site	Houston	Texas	United States	77030
53	Novo Nordisk Investigational Site	Humble	Texas	United States	77338
54	Novo Nordisk Investigational Site	Round Rock	Texas	United States	78681
55	Novo Nordisk Investigational Site	Schertz	Texas	United States	78154
56	Novo Nordisk Investigational Site	Spokane	Washington	United States	99201
57	Novo Nordisk Investigational Site	Curitiba	Parana	Brazil	80030-110
58	Novo Nordisk Investigational Site	Porto Alegre	Rio Grande Do Sul	Brazil	90035-170
59	Novo Nordisk Investigational Site	São Paulo	Sao Paulo	Brazil	01228-000
60	Novo Nordisk Investigational Site	Ahmedabad	Gujarat	India	380008
61	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560 017
62	Novo Nordisk Investigational Site	Indore	Madhya Pradesh	India	452010
63	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411004
64	Novo Nordisk Investigational Site	Jaipur	Rajasthan	India	302006
65	Novo Nordisk Investigational Site	Coimbatore	Tamil Nadu	India	641009
66	Novo Nordisk Investigational Site	Hyderabad	Telengana	India	500003
67	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700080
68	Novo Nordisk Investigational Site	New Delhi		India	110001
69	Novo Nordisk Investigational Site	Haifa		Israel	35152
70	Novo Nordisk Investigational Site	Kfar Saba		Israel	44281
71	Novo Nordisk Investigational Site	Tel Hashomer		Israel	52621
72	Novo Nordisk Investigational Site	Tel-Aviv		Israel	62038
73	Novo Nordisk Investigational Site	Ponce		Puerto Rico	00716
74	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	190013
75	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	190068
76	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	195197
77	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	199226
78	Novo Nordisk Investigational Site	St. Petersburg		Russian Federation	194354
79	Novo Nordisk Investigational Site	Al Ain		United Arab Emirates	1006
80	Novo Nordisk Investigational Site	Dubai		United Arab Emirates	7272
81	Novo Nordisk Investigational Site	Umm Al Quwain		United Arab Emirates	24
82	Novo Nordisk Investigational Site	Umm Al Quwain		United Arab Emirates	499

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Sep 26, 2018
• Statistical Analysis Plan - Sep 26, 2018

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02964247
• Other Study ID Numbers: NN2211-4315; U1111-1184-8086
• First Posted: Nov 16, 2016
• Last Update Posted: Nov 17, 2020
• Last Verified: Oct 1, 2020

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

Study Results

Participant Flow

Recruitment Details	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.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	203	100
Exposed to Trial Product	202	100
COMPLETED	200	98
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Liraglutide	Placebo	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	203	100	303
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.72 (10.08)	56.03 (9.89)	55.15 (10.02)
Sex: Female, Male (Count of Participants)
Female	78 38.4%	42 42%	120 39.6%
Male	125 61.6%	58 58%	183 60.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	59 29.1%	35 35%	94 31%
Not Hispanic or Latino	144 70.9%	65 65%	209 69%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	0 0%	1 1%	1 0.3%
Asian	38 18.7%	15 15%	53 17.5%
Native Hawaiian or Other Pacific Islander	1 0.5%	0 0%	1 0.3%
Black or African American	12 5.9%	5 5%	17 5.6%
White	131 64.5%	59 59%	190 62.7%
Other	21 10.3%	20 20%	41 13.5%

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c
Description	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.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
in-trial obs. period	-1.00 (0.86)	-0.32 (0.83)
on-treatment without rescue medication obs. period	-1.05 (0.85)	-0.35 (0.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments	Statistical analysis for the primary estimand. Primary estimand: treatment effect (effectiveness) based on the FAS using week 26 measurements from the in-trial observation period. The change in HbA1c from baseline to week 26 were analysed using a pattern mixture model with multiple imputation to impute missing data, with treatment, country and the stratification factor (metformin use at baseline: yes vs. no) as categorical fixed effects and baseline HbA1c as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.68
	Confidence Interval	(2-Sided) 95%; -0.89 to -0.48
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments	Liraglutide - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments	Statistical analysis for the secondary estimand.The change in HbA1c from baseline up to and including week 26 at scheduled time points were analysed using MMRM with treatment, country and the stratification factor (metformin use at baseline: yes vs. no) as categorical fixed effects and baseline HbA1c as covariate, all nested within visit.
	Type of Statistical Test	Superiority
	Comments	Test was not controlled for type I error. Secondary estimand: treatment effect (efficacy) based on the FAS using post baseline measurements up to and including week 26 from the on-treatment without rescue medication obs. period.
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.74
	Confidence Interval	(2-Sided) 95%; -0.94 to -0.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments	Liraglutide - Placebo

2. Secondary Outcome

Title	Change in Body Weight
Description	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.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
in-trial obs. period	-2.84 (3.83)	-2.02 (3.32)
on-treatment without rescue medication obs. period	-2.89 (3.81)	-2.09 (2.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments	Statistical analysis for the primary estimand. Primary estimand: treatment effect (effectiveness) based on the FAS using week 26 measurements from the in-trial observation period. The change in body weight from baseline to week 26 were analysed using a pattern mixture model with multiple imputation to impute missing data, with treatment, country and the stratification factor (metformin use at baseline: yes vs. no) as categorical fixed effects and baseline body weight as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.077
	Comments
	Method	pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.82
	Confidence Interval	(2-Sided) 95%; -1.73 to 0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.46
	Estimation Comments	Liraglutide - Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide, Placebo
	Comments	Statistical analysis for the secondary estimand. The change in body weight from baseline up to and including week 26 at scheduled time points were analysed using MMRM with treatment, country and the stratification factor (metformin use at baseline: yes vs. no) as categorical fixed effects and baseline body weight as covariate, all nested within visit.
	Type of Statistical Test	Superiority
	Comments	Test was not controlled for type I error. Secondary estimand: treatment effect (efficacy) based on the FAS using post baseline measurements up to and including week 26 from the on-treatment without rescue medication obs. period.
Statistical Test of Hypothesis	p-Value	0.062
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.86
	Confidence Interval	(2-Sided) 95%; -1.77 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.46
	Estimation Comments	Liraglutide - Placebo

3. Secondary Outcome

Title	Change in Fasting Plasma Glucose
Description	Change from baseline (week 0) to week 26 in fasting plasma glucose ('in-trial' observation period)
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Mean (Standard Deviation) [milligram/dL]	-27.00 (35.01)	-11.97 (45.20)

4. Secondary Outcome

Title	Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target
Description	Percentage of subjects who achieve HbA1c below 7.0% (53 mmol/mol), American Diabetes Association target, after 26 weeks ('in-trial' observation period)
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	195	95
Yes	51.79 25.5%	23.16 23.2%
No	48.21 23.7%	76.84 76.8%

5. Secondary Outcome

Title	Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target
Description	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)
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	195	95
Yes	34.36 16.9%	9.47 9.5%
No	65.64 32.3%	90.53 90.5%

6. Secondary Outcome

Title	Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain.
Description	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)
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	195	94
Yes	47.69 23.5%	19.15 19.2%
No	52.31 25.8%	80.85 80.9%

7. Secondary Outcome

Title	Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and Weight Loss Above or Equal to 3%.
Description	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)
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	195	94
Yes	29.74 14.7%	7.45 7.5%
No	70.26 34.6%	92.55 92.6%

8. Secondary Outcome

Title	Change in Self-measured Plasma Glucose 7-point Profile - Mean 7-point Profile
Description	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).
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Mean (Standard Deviation) [milligram/dL]	-33.93 (37.17)	-18.85 (40.81)

9. Secondary Outcome

Title	Change in Self-measured Plasma Glucose 7-point Profile - Mean Post Prandial Increments (Over All Meals)
Description	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)
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Mean (Standard Deviation) [milligram/dL]	-11.06 (41.29)	-4.44 (44.77)

10. Secondary Outcome

Title	Change in Body Mass Index (BMI)
Description	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)
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Mean (Standard Deviation) [kg/m^2]	-1.02 (1.40)	-0.72 (1.20)

11. Secondary Outcome

Title	Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain
Description	Percentage of subjects who achieve HbA1c below 7.0% (53 mmol/mol) and no weight gain, after 26 week ('in-trial' observation period).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	195	94
Yes	47.69 23.5%	19.15 19.2%
No	52.31 25.8%	80.85 80.9%

12. Secondary Outcome

Title	Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), no Weight Gain and Systolic Blood Pressure Below 140 mmHg.
Description	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)
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	195	94
Yes	42.05 20.7%	18.09 18.1%
No	57.95 28.5%	81.91 81.9%

13. Secondary Outcome

Title	Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol)
Description	Percentage of subjects who achieve HbA1c reduction above or equal to 1% (11mmol/mol), after 26 weeks ('in-trial' observation period)
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	195	95
Yes	52.31 25.8%	16.84 16.8%
No	47.69 23.5%	83.16 83.2%

14. Secondary Outcome

Title	Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and no Weight Gain
Description	Percentage of subjects who achieve HbA1c reduction above or equal to 1% (11mmol/mol) and no weight gain, after 26 weeks.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	195	94
Yes	45.13 22.2%	14.89 14.9%
No	54.87 27%	85.11 85.1%

15. Secondary Outcome

Title	Number of Treatment Emergent Adverse Events
Description	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.
Time Frame	Week 0 - 26 + 7 days

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	202	100
Number [Events]	426	106

16. Secondary Outcome

Title	Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes
Description	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.
Time Frame	Week 0 - 26

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	202	100
Number [Episodes]	0	3

17. Secondary Outcome

Title	Change in Fasting Blood Lipids - Total Cholesterol
Description	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.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.95 (45.1)	0.99 (42.3)

18. Secondary Outcome

Title	Change in Fasting Blood Lipids - Low Density Lipoprotein (LDL) Cholesterol
Description	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.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.97 (58.6)	1.01 (54.1)

19. Secondary Outcome

Title	Change in Fasting Blood Lipids - High Density Lipoprotein (HDL) Cholesterol
Description	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.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	1.05 (41.4)	1.01 (39.7)

20. Secondary Outcome

Title	Change in Fasting Blood Lipids - Very Low Density Lipoprotein (VLDL) Cholesterol
Description	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.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.83 (69.0)	0.94 (64.5)

21. Secondary Outcome

Title	Change in Fasting Blood Lipids-triglycerides
Description	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.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.81 (71.5)	0.93 (70.0)

22. Secondary Outcome

Title	Change in Fasting Blood Lipids- Free Fatty Acids (FFA)
Description	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.
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.80 (86.6)	0.86 (92.0)

23. Secondary Outcome

Title	Change in Waist Circumference
Description	Change from baseline (week 0) to week 26 in waist circumference ('in-trial' observation period).
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Mean (Standard Deviation) [cm]	-4.28 (11.19)	-1.77 (4.42)

24. Secondary Outcome

Title	Change in Systolic Blood Pressure
Description	Change from baseline (week 0) in systolic blood pressure after 26 weeks ('in-trial' observation period).
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Mean (Standard Deviation) [mmHg]	-1.95 (13.42)	-3.35 (12.36)

25. Secondary Outcome

Title	Change in Diastolic Blood Pressure
Description	Change from baseline (week 0) in diastolic blood pressure after 26 weeks ('in-trial' observation period).
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	203	100
Mean (Standard Deviation) [mmHg]	-0.72 (8.04)	-1.12 (8.55)

26. Secondary Outcome

Title	Subjects Who Achieve Weight Loss by 3% or More
Description	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).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Liraglutide	Placebo
Arm/Group Description	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.	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.
Measure Participants	196	97
Yes	46.43 22.9%	41.24 41.2%
No	53.57 26.4%	58.76 58.8%

Adverse Events

Time Frame	Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days
Adverse Event Reporting Description	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.
Arm/Group Title	Liraglutide		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Liraglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/202 (0%)		0/100 (0%)
Serious Adverse Events
	Liraglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/202 (2.5%)		1/100 (1%)
Cardiac disorders
Angina unstable	1/202 (0.5%)	1	0/100 (0%)	0
Cardiac failure congestive	1/202 (0.5%)	1	0/100 (0%)	0
Congestive cardiomyopathy	1/202 (0.5%)	1	0/100 (0%)	0
Eye disorders
Eyelid cyst	1/202 (0.5%)	1	0/100 (0%)	0
Gastrointestinal disorders
Haemorrhoids	1/202 (0.5%)	1	0/100 (0%)	0
Lower gastrointestinal haemorrhage	1/202 (0.5%)	1	0/100 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/202 (0.5%)	1	0/100 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/202 (0%)	0	1/100 (1%)	1
Ureterolithiasis	0/202 (0%)	0	1/100 (1%)	1
Other (Not Including Serious) Adverse Events
	Liraglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	87/202 (43.1%)		8/100 (8%)
Gastrointestinal disorders
Constipation	18/202 (8.9%)	19	0/100 (0%)	0
Diarrhoea	19/202 (9.4%)	24	3/100 (3%)	3
Nausea	53/202 (26.2%)	61	6/100 (6%)	8
Vomiting	17/202 (8.4%)	20	2/100 (2%)	2
Metabolism and nutrition disorders
Decreased appetite	19/202 (9.4%)	19	0/100 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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