Diabetes, Diabetes Mellitus, Type 2
Conditions
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.
Interventions
DRUGliraglutide
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
DRUGplacebo
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
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. * Male or female, age 18 years or older at the time of signing informed consent. * Diagnosed with type 2 diabetes mellitus. * HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive). * Stable dose of an SGLT-2 inhibitor as monotherapy or in combination (including fixed-dose drug combination) with a stable dose of metformin (1500 mg or more, or maximum tolerated dose) for at least 90 days prior to the day of screening. All medications in compliance with current local label. * Body mass index of 20 kg/m\^2 or above.
Exclusion criteria
* Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice). * History of diabetic ketoacidosis while being treated with SGLT2 inhibitors. * Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of less than 60 mL/min/1.73m\^2 as defined by Kidney Disease Improving Global Outcomes (KDIGO) classification using isotope dilution mass spectrometry (IDMS) for serum creatinine measured at screening. * Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days during the 90 days prior to screening is allowed. * Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative. * History or presence of pancreatitis (acute or chronic). * Impaired liver function, defined as ALT 2.5 or more times upper normal limit at screening. * Subjects presently classified as being in New York Heart Association (NYHA) Class IV.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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. |
Countries
Brazil, India, Israel, Puerto Rico, Russia, United Arab Emirates, United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Liraglutide Eligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication.
A follow-up visit was scheduled one week after the end of treatment. | 203 |
| Placebo Eligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication.
A follow-up visit was scheduled one week after the end of treatment. | 100 |
| Total | 303 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Liraglutide |
|---|---|---|---|
| Age, Continuous | 56.03 Years STANDARD_DEVIATION 9.89 | 55.15 Years STANDARD_DEVIATION 10.02 | 54.72 Years STANDARD_DEVIATION 10.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 94 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 209 Participants | 144 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 15 Participants | 53 Participants | 38 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 17 Participants | 12 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 20 Participants | 41 Participants | 21 Participants |
| Race/Ethnicity, Customized White | 59 Participants | 190 Participants | 131 Participants |
| Sex: Female, Male Female | 42 Participants | 120 Participants | 78 Participants |
| Sex: Female, Male Male | 58 Participants | 183 Participants | 125 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 202 | 0 / 100 |
| other Total, other adverse events | 87 / 202 | 8 / 100 |
| serious Total, serious adverse events | 5 / 202 | 1 / 100 |
Outcome results
Primary
Change in HbA1c
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide | Change in HbA1c | in-trial obs. period | -1.00 Percentage of HbA1c | Standard Deviation 0.86 |
| Liraglutide | Change in HbA1c | on-treatment without rescue medication obs. period | -1.05 Percentage of HbA1c | Standard Deviation 0.85 |
| Placebo | Change in HbA1c | in-trial obs. period | -0.32 Percentage of HbA1c | Standard Deviation 0.83 |
| Placebo | Change in HbA1c | on-treatment without rescue medication obs. period | -0.35 Percentage of HbA1c | Standard Deviation 0.8 |
Comparison: 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.p-value: <0.00195% CI: [-0.89, -0.48]pattern mixture model
Comparison: 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.p-value: <0.00195% CI: [-0.94, -0.53]Mixed Models Analysis
Secondary
Change in Body Mass Index (BMI)
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Body Mass Index (BMI) | -1.02 kg/m^2 | Standard Deviation 1.4 |
| Placebo | Change in Body Mass Index (BMI) | -0.72 kg/m^2 | Standard Deviation 1.2 |
Secondary
Change in Body Weight
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liraglutide | Change in Body Weight | in-trial obs. period | -2.84 Kg | Standard Deviation 3.83 |
| Liraglutide | Change in Body Weight | on-treatment without rescue medication obs. period | -2.89 Kg | Standard Deviation 3.81 |
| Placebo | Change in Body Weight | in-trial obs. period | -2.02 Kg | Standard Deviation 3.32 |
| Placebo | Change in Body Weight | on-treatment without rescue medication obs. period | -2.09 Kg | Standard Deviation 2.96 |
Comparison: 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.p-value: 0.07795% CI: [-1.73, 0.09]pattern mixture model
Comparison: 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.p-value: 0.06295% CI: [-1.77, 0.04]Mixed Models Analysis
Secondary
Change in Diastolic Blood Pressure
Change from baseline (week 0) in diastolic blood pressure after 26 weeks ('in-trial' observation period).
Time frame: Week 0, Week 26
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Diastolic Blood Pressure | -0.72 mmHg | Standard Deviation 8.04 |
| Placebo | Change in Diastolic Blood Pressure | -1.12 mmHg | Standard Deviation 8.55 |
Secondary
Change in Fasting Blood Lipids- Free Fatty Acids (FFA)
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Fasting Blood Lipids- Free Fatty Acids (FFA) | 0.80 Ratio | Geometric Coefficient of Variation 86.6 |
| Placebo | Change in Fasting Blood Lipids- Free Fatty Acids (FFA) | 0.86 Ratio | Geometric Coefficient of Variation 92 |
Secondary
Change in Fasting Blood Lipids - High Density Lipoprotein (HDL) Cholesterol
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Fasting Blood Lipids - High Density Lipoprotein (HDL) Cholesterol | 1.05 Ratio | Geometric Coefficient of Variation 41.4 |
| Placebo | Change in Fasting Blood Lipids - High Density Lipoprotein (HDL) Cholesterol | 1.01 Ratio | Geometric Coefficient of Variation 39.7 |
Secondary
Change in Fasting Blood Lipids - Low Density Lipoprotein (LDL) Cholesterol
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Fasting Blood Lipids - Low Density Lipoprotein (LDL) Cholesterol | 0.97 Ratio | Geometric Coefficient of Variation 58.6 |
| Placebo | Change in Fasting Blood Lipids - Low Density Lipoprotein (LDL) Cholesterol | 1.01 Ratio | Geometric Coefficient of Variation 54.1 |
Secondary
Change in Fasting Blood Lipids - Total Cholesterol
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Fasting Blood Lipids - Total Cholesterol | 0.95 Ratio | Geometric Coefficient of Variation 45.1 |
| Placebo | Change in Fasting Blood Lipids - Total Cholesterol | 0.99 Ratio | Geometric Coefficient of Variation 42.3 |
Secondary
Change in Fasting Blood Lipids-triglycerides
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Fasting Blood Lipids-triglycerides | 0.81 Ratio | Geometric Coefficient of Variation 71.5 |
| Placebo | Change in Fasting Blood Lipids-triglycerides | 0.93 Ratio | Geometric Coefficient of Variation 70 |
Secondary
Change in Fasting Blood Lipids - Very Low Density Lipoprotein (VLDL) Cholesterol
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Fasting Blood Lipids - Very Low Density Lipoprotein (VLDL) Cholesterol | 0.83 Ratio | Geometric Coefficient of Variation 69 |
| Placebo | Change in Fasting Blood Lipids - Very Low Density Lipoprotein (VLDL) Cholesterol | 0.94 Ratio | Geometric Coefficient of Variation 64.5 |
Secondary
Change in Fasting Plasma Glucose
Change from baseline (week 0) to week 26 in fasting plasma glucose ('in-trial' observation period)
Time frame: Week 0, Week 26
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Fasting Plasma Glucose | -27.00 milligram/dL | Standard Deviation 35.01 |
| Placebo | Change in Fasting Plasma Glucose | -11.97 milligram/dL | Standard Deviation 45.2 |
Secondary
Change in Self-measured Plasma Glucose 7-point Profile - Mean 7-point Profile
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Self-measured Plasma Glucose 7-point Profile - Mean 7-point Profile | -33.93 milligram/dL | Standard Deviation 37.17 |
| Placebo | Change in Self-measured Plasma Glucose 7-point Profile - Mean 7-point Profile | -18.85 milligram/dL | Standard Deviation 40.81 |
Secondary
Change in Self-measured Plasma Glucose 7-point Profile - Mean Post Prandial Increments (Over All Meals)
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Self-measured Plasma Glucose 7-point Profile - Mean Post Prandial Increments (Over All Meals) | -11.06 milligram/dL | Standard Deviation 41.29 |
| Placebo | Change in Self-measured Plasma Glucose 7-point Profile - Mean Post Prandial Increments (Over All Meals) | -4.44 milligram/dL | Standard Deviation 44.77 |
Secondary
Change in Systolic Blood Pressure
Change from baseline (week 0) in systolic blood pressure after 26 weeks ('in-trial' observation period).
Time frame: Week 0, Week 26
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Systolic Blood Pressure | -1.95 mmHg | Standard Deviation 13.42 |
| Placebo | Change in Systolic Blood Pressure | -3.35 mmHg | Standard Deviation 12.36 |
Secondary
Change in Waist Circumference
Change from baseline (week 0) to week 26 in waist circumference ('in-trial' observation period).
Time frame: Week 0, Week 26
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change in Waist Circumference | -4.28 cm | Standard Deviation 11.19 |
| Placebo | Change in Waist Circumference | -1.77 cm | Standard Deviation 4.42 |
Secondary
Number of Treatment Emergent Adverse Events
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
Population: Safety analysis set (SAS) includes all subjects exposed to at least one dose of trial product. Subjects in the SAS contribute to the evaluation based on the trial product received for the period they were on-treatment, referred to as contributing to the evaluation 'as treated'. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide | Number of Treatment Emergent Adverse Events | 426 Events |
| Placebo | Number of Treatment Emergent Adverse Events | 106 Events |
Secondary
Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes
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
Population: Safety analysis set (SAS) includes all subjects exposed to at least one dose of trial product. Subjects in the SAS contribute to the evaluation based on the trial product received for the period they were on-treatment, referred to as contributing to the evaluation 'as treated'. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide | Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes | 0 Episodes |
| Placebo | Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes | 3 Episodes |
Secondary
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target | Yes | 51.79 Percentage of Participants |
| Liraglutide | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target | No | 48.21 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target | Yes | 23.16 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target | No | 76.84 Percentage of Participants |
Secondary
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain | Yes | 47.69 Percentage of Participants |
| Liraglutide | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain | No | 52.31 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain | Yes | 19.15 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain | No | 80.85 Percentage of Participants |
Secondary
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), no Weight Gain and Systolic Blood Pressure Below 140 mmHg.
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), no Weight Gain and Systolic Blood Pressure Below 140 mmHg. | Yes | 42.05 Percentage of Participants |
| Liraglutide | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), no Weight Gain and Systolic Blood Pressure Below 140 mmHg. | No | 57.95 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), no Weight Gain and Systolic Blood Pressure Below 140 mmHg. | Yes | 18.09 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), no Weight Gain and Systolic Blood Pressure Below 140 mmHg. | No | 81.91 Percentage of Participants |
Secondary
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain.
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain. | Yes | 47.69 Percentage of Participants |
| Liraglutide | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain. | No | 52.31 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain. | Yes | 19.15 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain. | No | 80.85 Percentage of Participants |
Secondary
Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide | Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target | Yes | 34.36 Percentage of Participants |
| Liraglutide | Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target | No | 65.64 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target | Yes | 9.47 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target | No | 90.53 Percentage of Participants |
Secondary
Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol)
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) | Yes | 52.31 Percentage of Participants |
| Liraglutide | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) | No | 47.69 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) | Yes | 16.84 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) | No | 83.16 Percentage of Participants |
Secondary
Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and no Weight Gain
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and no Weight Gain | Yes | 45.13 Percentage of Participants |
| Liraglutide | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and no Weight Gain | No | 54.87 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and no Weight Gain | Yes | 14.89 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and no Weight Gain | No | 85.11 Percentage of Participants |
Secondary
Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and Weight Loss Above or Equal to 3%.
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and Weight Loss Above or Equal to 3%. | Yes | 29.74 Percentage of Participants |
| Liraglutide | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and Weight Loss Above or Equal to 3%. | No | 70.26 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and Weight Loss Above or Equal to 3%. | Yes | 7.45 Percentage of Participants |
| Placebo | Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and Weight Loss Above or Equal to 3%. | No | 92.55 Percentage of Participants |
Secondary
Subjects Who Achieve Weight Loss by 3% or More
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
Population: Full analysis set (FAS) includes all randomised subjects. 'Number Analyzed' = subjects with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liraglutide | Subjects Who Achieve Weight Loss by 3% or More | Yes | 46.43 Percentage of participants |
| Liraglutide | Subjects Who Achieve Weight Loss by 3% or More | No | 53.57 Percentage of participants |
| Placebo | Subjects Who Achieve Weight Loss by 3% or More | Yes | 41.24 Percentage of participants |
| Placebo | Subjects Who Achieve Weight Loss by 3% or More | No | 58.76 Percentage of participants |