LIRA-ADD2SGLT2i - Liraglutide Versus Placebo as add-on to SGLT2 Inhibitors.
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 |
---|---|---|
|
Phase 3 |
Study Design
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
- 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
- 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.
- 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)
- 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)
- 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)
- 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)
- 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)
- 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).
- 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)
- 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)
- 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).
- 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)
- 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)
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Change in Waist Circumference [Week 0, Week 26]
Change from baseline (week 0) to week 26 in waist circumference ('in-trial' observation period).
- 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).
- 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).
- 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
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)
More Information
Publications
None provided.- NN2211-4315
- U1111-1184-8086
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. |
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Pre-assignment Detail |
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
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 |
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 |
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)
|
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%
|
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%
|
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%
|
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%
|
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)
|
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)
|
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)
|
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%
|
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%
|
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%
|
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%
|
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
|
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
|
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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)
|
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 |
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Liraglutide | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/202 (0%) | 0/100 (0%) | ||
Serious Adverse Events |
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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 |
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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
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.
Results Point of Contact
Name/Title | Clinical Reporting Anchor and Disclosure (1452) |
---|---|
Organization | Novo Nordisk A/S |
Phone | (+1) 866-867-7178 |
clinicaltrials@novonordisk.com |
- NN2211-4315
- U1111-1184-8086