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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01541215




Registration number
NCT01541215
Ethics application status
Date submitted
23/02/2012
Date registered
29/02/2012
Date last updated
2/06/2020

Titles & IDs
Public title
Efficacy and Safety of Liraglutide in Combination With Metformin Compared to Metformin Alone, in Children and Adolescents With Type 2 Diabetes
Scientific title
Efficacy and Safety of Liraglutide in Combination With Metformin Versus Metformin Monotherapy on Glycaemic Control in Children and Adolescents With Type 2 Diabetes
Secondary ID [1] 0 0
2011-002605-29
Secondary ID [2] 0 0
NN2211-3659
Universal Trial Number (UTN)
Trial acronym
Ellipseā„¢
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 0 0
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - liraglutide
Treatment: Drugs - placebo
Treatment: Drugs - metformin

Experimental: Lira + Met -

Placebo Comparator: Placebo + Met -


Treatment: Drugs: liraglutide
Administered subcutaneously (s.c., under the skin) once daily.1.8 mg or maximum tolerated dose (MTD: 0.6 mg, 1.2 mg, 1.8 mg) for 26 weeks. Subjects will continue treatment in a 26 week open-labelled extension. Rescue treatment will be allowed if rescue criteria are met.

Treatment: Drugs: placebo
Administered subcutaneously (s.c., under the skin) once daily for 26 weeks. Subjects will discontinue placebo treatment in the open-labelled extension. Rescue treatment will be allowed if rescue criteria are met.

Treatment: Drugs: metformin
Tablets administered for 26 weeks. Maximum tolerated dose (MTD) between 1000-2000 mg at the discretion of the investigator. Subjects will continue treatment in a 26 week open-labelled extension.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in HbA1c (Glycosylated Haemoglobin) - Change in HbA1c from baseline to week 26. All available data were used for the primary analysis, including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [1] 0 0
Week 0, week 26
Secondary outcome [1] 0 0
Change From Baseline in Fasting Plasma Glucose (FPG) - Change in FPG from baseline to week 26. All available data were used for the analysis, including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [1] 0 0
Week 0, week 26
Secondary outcome [2] 0 0
Number of Subjects Having HbA1c Below 7.0% - Percentage of subjects having HbA1c <7.0%. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [2] 0 0
Week 26
Secondary outcome [3] 0 0
Change From Baseline in Body Mass Index (BMI) Standard Deviation Score (SDS) - Change in BMI SDS from baseline to week 26. BMI SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the world health organisation (WHO) Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [3] 0 0
Week 0, week 26
Secondary outcome [4] 0 0
Number of Subjects Having HbA1c Below 7.0% - Number of subjects achieving HbA1c <7.0% after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [4] 0 0
Week 52
Secondary outcome [5] 0 0
Number of Subjects Having HbA1c Maximum 6.5% - Number of subjects achieving HbA1c <=6.5% after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [5] 0 0
Week 26
Secondary outcome [6] 0 0
Number of Subjects Having HbA1c Maximum 6.5% - Number of subjects achieving HbA1c <=6.5% after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [6] 0 0
Week 52
Secondary outcome [7] 0 0
Number of Subjects Having HbA1c Below 7.0% Without Severe or Minor Hypoglycaemic Episodes - Number of subjects achieving HbA1c <7.0% without severe or minor hypoglycaemic episodes after 26 weeks.
Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
Minor hypoglycaemia was defined as meeting either of the below criteria:
an episode with symptoms consistent with hypoglycaemia with confirmation by blood glucose <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL), and which was handled by the subject him/herself
any asymptomatic blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose value <3.1 mmol/L (56 mg/dL) All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [7] 0 0
Week 26
Secondary outcome [8] 0 0
Number of Subjects Having HbA1c Below 7.0% Without Severe or Minor Hypoglycaemic Episodes - Number of subjects achieving HbA1c <7.0% without severe or minor hypoglycaemic episodes after 52 weeks.
Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.
Minor hypoglycaemia was defined as meeting either of the below criteria:
an episode with symptoms consistent with hypoglycaemia with confirmation by blood glucose <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL), and which was handled by the subject him/herself
any asymptomatic blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose value <3.1 mmol/L (56 mg/dL) All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [8] 0 0
Week 52
Secondary outcome [9] 0 0
Number of Subjects Having HbA1c Below 7.5% - Number of subjects achieving HbA1c <7.5% after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [9] 0 0
Week 26
Secondary outcome [10] 0 0
Number of Subjects Having HbA1c Below 7.5% - Number of subjects achieving HbA1c <7.5% after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [10] 0 0
Week 52
Secondary outcome [11] 0 0
Change in HbA1c - Change in HbA1c from baseline to week 52. All available data were used for the analysis, including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [11] 0 0
Week 0, week 52
Secondary outcome [12] 0 0
Change in FPG - Change in FPG from baseline to week 52. All available data were used for the analysis, including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [12] 0 0
Week 0, week 52
Secondary outcome [13] 0 0
Change in Mean 7-point Self-measured Plasma Glucose - Change in mean 7-point self-measured plasma glucose after 26 weeks. Subjects were instructed to measure their plasma glucose at following 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 and at bedtime. Mean 7-point SMPG was defined as the area under the profile (calculated using the trapezoidal method) divided by time. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [13] 0 0
Week 0, week 26
Secondary outcome [14] 0 0
Change From Baseline in 7-point Self-measured Plasma Glucose - Change in mean 7-point self-measured plasma glucose after 52 weeks. Subjects were instructed to measure their plasma glucose at following 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 and at bedtime. Mean 7-point SMPG was defined as the area under the profile (calculated using the trapezoidal method) divided by time. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [14] 0 0
Week 0, week 52
Secondary outcome [15] 0 0
Change in Post-prandial Increments (From Before Meal to 90 Min After Breakfast, Lunch, and Dinner) - Change in post-prandial increments (from before meal to 90 min after breakfast, lunch, and dinner) after 26 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [15] 0 0
Week 0, week 26
Secondary outcome [16] 0 0
Change in Post-prandial Increments (From Before Meal to 90 Min After Breakfast, Lunch, and Dinner) - Change in post-prandial increments (from before meal to 90 min after breakfast, lunch, and dinner) after 52 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [16] 0 0
Week 0, week 52
Secondary outcome [17] 0 0
Change in Mean Post-prandial Increment Across All Three Meals (Breakfast, Lunch, and Dinner) - Change in mean post-prandial increment across all three meals (breakfast, lunch, and dinner) after 26 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [17] 0 0
Week 0, week 26
Secondary outcome [18] 0 0
Change in Mean Post-prandial Increment Across All Three Meals (Breakfast, Lunch, and Dinner) - Change in mean post-prandial increment across all three meals (breakfast, lunch, and dinner) after 52 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [18] 0 0
Week 0, week 52
Secondary outcome [19] 0 0
Change From Baseline in Body Weight - Change from baseline in body weight after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [19] 0 0
Week 0, week 26
Secondary outcome [20] 0 0
Change From Baseline in Body Weight - Change from baseline in body weight after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [20] 0 0
Week 0, week 52
Secondary outcome [21] 0 0
Change From Baseline in BMI Standard Deviation Score (SDS) - Change in BMI SDS from baseline to week 52. BMI SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [21] 0 0
Week 0, week 52
Secondary outcome [22] 0 0
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) - Change in blood pressure (systolic and diastolic blood pressure) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [22] 0 0
Week 0, week 26
Secondary outcome [23] 0 0
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) - Change in blood pressure (systolic and diastolic blood pressure) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [23] 0 0
Week 0, week 52
Secondary outcome [24] 0 0
Ratio to Baseline: Fasting Insulin - Ratio to baseline (fasting insulin) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [24] 0 0
Week 0, week 26
Secondary outcome [25] 0 0
Ratio to Baseline: Fasting Insulin - Ratio to baseline (fasting insulin) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [25] 0 0
Week 0, week 52
Secondary outcome [26] 0 0
Ratio to Baseline: Fasting Pro-insulin - Ratio to baseline (fasting pro-insulin) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [26] 0 0
Week 0, week 26
Secondary outcome [27] 0 0
Ratio to Baseline: Fasting Pro-insulin - Ratio to baseline (fasting pro-insulin) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [27] 0 0
Week 0, week 52
Secondary outcome [28] 0 0
Ratio to Baseline: Pro-insulin/Insulin Ratio - Ratio to baseline (Pro-insulin/insulin ratio) after week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [28] 0 0
Week 0, week 26
Secondary outcome [29] 0 0
Ratio to Baseline: Pro-insulin/Insulin Ratio - Ratio to baseline (Pro-insulin/insulin ratio) after week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [29] 0 0
Week 0, week 52
Secondary outcome [30] 0 0
Ratio to Baseline: Fasting Glucagon - Ratio to baseline (fasting glucagon) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [30] 0 0
Week 0, week 26
Secondary outcome [31] 0 0
Ratio to Baseline: Fasting Glucagon - Ratio to baseline (fasting glucagon) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [31] 0 0
Week 0, week 52
Secondary outcome [32] 0 0
Ratio to Baseline: Fasting C-peptide - Ratio to baseline (fasting C-peptide) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [32] 0 0
Week 0, week 26
Secondary outcome [33] 0 0
Ratio to Baseline: Fasting C-peptide - Ratio to baseline (fasting C-peptide) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [33] 0 0
Week 0, week 52
Secondary outcome [34] 0 0
Ratio to Baseline: Homeostasis Model Assessment of Beta-cell Function (HOMA-B) - Ratio to baseline (HOMA-B) after 26 weeks. HOMA-B is an index of beta-cell function and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [34] 0 0
Week 0, week 26
Secondary outcome [35] 0 0
Ratio to Baseline: HOMA-B - Ratio to baseline (HOMA-B) after 52 weeks. HOMA-B is an index of beta-cell function and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [35] 0 0
Week 0, week 52
Secondary outcome [36] 0 0
Ratio to Baseline: Homeostasis Model Assessment as an Index of Insulin Resistance (HOMA-IR) - Ratio to baseline (HOMA-IR) after 26 weeks. HOMA-IR is an index of insulin resistance and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [36] 0 0
Week 0, week 26
Secondary outcome [37] 0 0
Ratio to Baseline: HOMA-IR - Ratio to baseline (HOMA-IR) after 52 weeks. HOMA-IR is an index of insulin resistance and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [37] 0 0
Week 0, week 52
Secondary outcome [38] 0 0
Ratio to Baseline: Total Cholesterol - Ratio to baseline (total cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [38] 0 0
Week 0, week 26
Secondary outcome [39] 0 0
Ratio to Baseline: Total Cholesterol - Ratio to baseline (total cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [39] 0 0
Week 0, week 52
Secondary outcome [40] 0 0
Ratio to Baseline: Low Density Lipoprotein (LDL) Cholesterol - Ratio to baseline (LDL cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [40] 0 0
Week 0, week 26
Secondary outcome [41] 0 0
Ratio to Baseline: LDL Cholesterol - Ratio to baseline (LDL cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [41] 0 0
Week 0, week 52
Secondary outcome [42] 0 0
Ratio to Baseline: Very Low-density Lipoprotein (VLDL) Cholesterol - Ratio to baseline (VLDL cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [42] 0 0
Week 0, week 26
Secondary outcome [43] 0 0
Ratio to Baseline: VLDL Cholesterol - Ratio to baseline (VLDL cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [43] 0 0
Week 0, week 52
Secondary outcome [44] 0 0
Ratio to Baseline: High-density Lipoprotein (HDL) Cholesterol - Ratio to baseline (HDL cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [44] 0 0
Week 0, week 26
Secondary outcome [45] 0 0
Ratio to Baseline: HDL Cholesterol - Ratio to baseline (HDL cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [45] 0 0
Week 0, week 52
Secondary outcome [46] 0 0
Ratio to Baseline: Triglycerides - Ratio to baseline (triglycerides) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [46] 0 0
Week 0, week 26
Secondary outcome [47] 0 0
Ratio to Baseline: Triglycerides - Ratio to baseline (triglycerides) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [47] 0 0
Week 0, week 52
Secondary outcome [48] 0 0
Ratio to Baseline: Free Fatty Acids - Ratio to baseline (free fatty acids) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [48] 0 0
Week 0, week 26
Secondary outcome [49] 0 0
Ratio to Baseline: Free Fatty Acids - Ratio to baseline (free fatty acids) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [49] 0 0
Week 0, week 52
Secondary outcome [50] 0 0
Change From Baseline in Pulse - Change from baseline in pulse 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [50] 0 0
Week 0, week 26
Secondary outcome [51] 0 0
Change From Baseline in Pulse - Change from baseline in pulse 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [51] 0 0
Week 0, week 52
Secondary outcome [52] 0 0
Change From Baseline in Height SDS - Change in height SDS from baseline to week 26. Height SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [52] 0 0
Week 0, week 26
Secondary outcome [53] 0 0
Change From Baseline in Height SDS - Change in height SDS from baseline to week 52. Height SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [53] 0 0
Week 0, week 52
Secondary outcome [54] 0 0
Change in Bone Age Assessment (X-ray of Left Hand and Wrist) - Change in bone age from baseline to week 52. If the baseline (week 0) bone age assessment indicated that all epiphyses were fused, then the assessment was not repeated at week 52.
Timepoint [54] 0 0
Week 0, week 52
Secondary outcome [55] 0 0
Pubertal Assessment/Progression (Tanner Staging) - Pubertal development was assessed in 3 areas (breast, penis and pubic hair development) by the Tanner staging in accordance with stages I-V. The Tanner staging assessment was no longer required to be performed once a subject reached the Tanner stage V, as judged by the investigator. Reported results are number of participants at different Tanner stages at week 0, week 26 and week 52.
Timepoint [55] 0 0
Week 0, week 26, week 52
Secondary outcome [56] 0 0
Growth (Height Velocity) - Growth (i.e., height velocity) is the change in height per year and is measured in cm/year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by the time (in days) between those measurement time points and multiplied by 365 days.
Timepoint [56] 0 0
Week 0, week 26
Secondary outcome [57] 0 0
Growth (Height Velocity) - Growth (i.e., height velocity) is the change in height per year and is measured in cm/year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by the time (in days) between those measurement time points and multiplied by 365 days.
Timepoint [57] 0 0
Week 0, week 52
Secondary outcome [58] 0 0
Height Velocity SDS - Height velocity SDS scores at week 26. Height velocity is change in height per year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [58] 0 0
Week 0, week 26
Secondary outcome [59] 0 0
Height Velocity SDS - Height velocity SDS scores at week 52. Height velocity is change in height per year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Timepoint [59] 0 0
Week 0, week 52
Secondary outcome [60] 0 0
Number of Hypoglycaemic Episodes - Total number of hypoglycaemic episodes according to American Diabetes Association (ADA) classification from baseline (week 0) to week 26.
Timepoint [60] 0 0
0-26 weeks
Secondary outcome [61] 0 0
Number of Hypoglycaemic Episodes - Total number of hypoglycaemic episodes according to American Diabetes Association (ADA) classification from baseline (week 0) to week 52.
Timepoint [61] 0 0
0-52 weeks
Secondary outcome [62] 0 0
Number of Adverse Events (Week 0-26) - Total number of adverse events during 26 weeks.
Timepoint [62] 0 0
0-26 weeks
Secondary outcome [63] 0 0
Number of Adverse Events (Week 0-52) - Total number of adverse events during entire treatment period.
Timepoint [63] 0 0
0-52 weeks
Secondary outcome [64] 0 0
Number of Serious Adverse Events (Week 0-26) - Total number of serious adverse events during 26 weeks.
Timepoint [64] 0 0
0-26 weeks
Secondary outcome [65] 0 0
Number of Serious Adverse Events (Week 0-52) - Total number of serious adverse events during entire treatment period.
Timepoint [65] 0 0
0-52 weeks
Secondary outcome [66] 0 0
Number of Adverse Events (Week 53-104) - This outcome is applicable only for the Liraglutide 1.8 mg treatment arm. Number of adverse events reported during follow-up 1 (week 53 to 104).
Timepoint [66] 0 0
Week 53-104
Secondary outcome [67] 0 0
Number of Serious Adverse Events (Week 53-104) - This outcome is applicable only for the Liraglutide 1.8 mg treatment arm. Number of serious adverse events reported during follow up 1 (week 53 to 104).
Timepoint [67] 0 0
Weeks 53-104
Secondary outcome [68] 0 0
Growth (Height Velocity)- Week 104 - Growth (i.e., height velocity) is the change in height per year and is measured in cm/year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by the time (in days) between those measurement time points and multiplied by 365 days. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.
Timepoint [68] 0 0
Week 0, week 104
Secondary outcome [69] 0 0
Height Velocity SDS- Week 104 - The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.
Timepoint [69] 0 0
Week 0, week 104
Secondary outcome [70] 0 0
Change From Week 52 in Height SDS- Week 104 - Change in height SDS from week 52 to week 104. Height SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.
Timepoint [70] 0 0
Week 52, week 104
Secondary outcome [71] 0 0
Change in Pubertal Assessment/Progression (Tanner Staging)- Week 104 - Pubertal development was assessed in 3 areas (breast, penis and pubic hair development) by the Tanner staging in accordance with stages I-V, where stage I represents "pre-adoloscent development" and stage V represents "pubertal development equivalent to that of an adult". The Tanner staging assessment was no longer required to be performed once a subject reached the Tanner stage V, as judged by the investigator. Reported results are number of subjects at different Tanner stages at week 52 and week 104. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.
Timepoint [71] 0 0
Week 52, week 104
Secondary outcome [72] 0 0
Change From Week 52 in Bone Age Assessment (X-ray of Left Hand and Wrist)- Week 104 - Change in bone age from week 52 to week 104. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.
Timepoint [72] 0 0
Week 52, week 104
Secondary outcome [73] 0 0
Number of Adverse Events (Week 53-156)
Timepoint [73] 0 0
Weeks 53-156
Secondary outcome [74] 0 0
Number of Serious Adverse Events (Week 53-156)
Timepoint [74] 0 0
Weeks 53-156
Secondary outcome [75] 0 0
Growth (Height Velocity)- Week 156
Timepoint [75] 0 0
Week 0, week 156
Secondary outcome [76] 0 0
Height Velocity SDS- Week 156
Timepoint [76] 0 0
Week 0, week 156
Secondary outcome [77] 0 0
Change From Week 52 in Height SDS- Week 156
Timepoint [77] 0 0
Week 52, week 156
Secondary outcome [78] 0 0
Pubertal Assessment/Progression (Tanner Staging)- Week 156
Timepoint [78] 0 0
Week 52, week 156
Secondary outcome [79] 0 0
Change in Bone Age Assessment (X-ray of Left Hand and Wrist)- Week 156
Timepoint [79] 0 0
Week 52, week 156

Eligibility
Key inclusion criteria
- Children and adolescents between the ages of 10-16 years. Subjects
cannot turn 17 years and 11 months before the end of treatment (52 weeks) - Diagnosis of
type 2 diabetes mellitus and treated for at least 30 days with: diet and exercise alone,
diet and exercise in combination with metformin monotherapy, diet and exercise in
combination with metformin and a stable (Stable is defined as basal insulin adjustments up
to 15%) dose of basal insulin, diet and exercise in combination with a stable (Stable is
defined as basal insulin adjustments up to 15%) dose of basal insulin - HbA1c: 7.0-11%
(inclusive) if diet and exercise treated or 6.5-11% (inclusive) if treated with metformin
as monotherapy, basal insulin as monotherapy or metformin and basal insulin in combination
- Body mass index (BMI) above 85% percentile of the general age and gender matched
population
Minimum age
10 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Type 1 diabetes - Maturity onset diabetes of the young
(MODY) - Use of any antidiabetic agent other than metformin and/or basal insulin within 90
days prior to screening - Recurrent severe hypoglycaemia or hypoglycaemic unawareness as
judged by the investigator - History of chronic pancreatitis or idiopathic acute
pancreatitis - Any clinically significant disorder, except for conditions associated with
type 2 diabetes history which in the investigator's opinion could interfere with results of
the trial - Uncontrolled hypertension, treated or untreated above 99th percentile for age
and gender in children - Known or suspected abuse of alcohol or drugs/narcotics

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Novo Nordisk Investigational Site - Ipswich
Recruitment postcode(s) [1] 0 0
4305 - Ipswich
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
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Arizona
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Indiana
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Iowa
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Kansas
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Kentucky
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Missouri
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Nevada
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New Jersey
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New York
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Ohio
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Pennsylvania
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South Carolina
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South Dakota
Country [25] 0 0
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Tennessee
Country [26] 0 0
United States of America
State/province [26] 0 0
Texas
Country [27] 0 0
United States of America
State/province [27] 0 0
Virginia
Country [28] 0 0
United States of America
State/province [28] 0 0
West Virginia
Country [29] 0 0
Austria
State/province [29] 0 0
Graz
Country [30] 0 0
Austria
State/province [30] 0 0
Innsbruck
Country [31] 0 0
Austria
State/province [31] 0 0
Salzburg
Country [32] 0 0
Austria
State/province [32] 0 0
Wels
Country [33] 0 0
Belgium
State/province [33] 0 0
Brussels
Country [34] 0 0
Belgium
State/province [34] 0 0
Leuven
Country [35] 0 0
Brazil
State/province [35] 0 0
Rio Grande Do Sul
Country [36] 0 0
Canada
State/province [36] 0 0
Alberta
Country [37] 0 0
Canada
State/province [37] 0 0
Manitoba
Country [38] 0 0
Canada
State/province [38] 0 0
Ontario
Country [39] 0 0
Canada
State/province [39] 0 0
Quebec
Country [40] 0 0
Croatia
State/province [40] 0 0
Rijeka
Country [41] 0 0
Croatia
State/province [41] 0 0
Zagreb
Country [42] 0 0
Denmark
State/province [42] 0 0
Herlev
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Denmark
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Næstved
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Egypt
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Alexandria
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Egypt
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Cairo
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Egypt
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Mansoura
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France
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Marseille
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France
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MONTPELLIER cedex 05
Country [49] 0 0
Germany
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Ludwigshafen
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Germany
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Mayen
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Greece
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Athens
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Greece
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Goudi/ Athens
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Greece
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Thessaloniki
Country [54] 0 0
Hungary
State/province [54] 0 0
Budapest
Country [55] 0 0
Hungary
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Miskolc
Country [56] 0 0
Hungary
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Szombathely
Country [57] 0 0
India
State/province [57] 0 0
Andhra Pradesh
Country [58] 0 0
India
State/province [58] 0 0
Karnataka
Country [59] 0 0
India
State/province [59] 0 0
Maharashtra
Country [60] 0 0
India
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New Delhi
Country [61] 0 0
India
State/province [61] 0 0
Punjab
Country [62] 0 0
India
State/province [62] 0 0
Rajasthan
Country [63] 0 0
India
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Tamil Nadu
Country [64] 0 0
India
State/province [64] 0 0
West Bengal
Country [65] 0 0
India
State/province [65] 0 0
Kolkata
Country [66] 0 0
Israel
State/province [66] 0 0
Beer Sheva
Country [67] 0 0
Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Tel Hashomer
Country [71] 0 0
Italy
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Roma
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Lebanon
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Hazmieh
Country [73] 0 0
Lebanon
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Lebanon - Beirut
Country [74] 0 0
Malaysia
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Kuala Lumpur
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Mexico
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Tamaulipas
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Mexico
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Puebla
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Morocco
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Fès
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Morocco
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Rabat
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Netherlands
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Den Bosch
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New Zealand
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Grafton
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North Macedonia
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Skopje
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Norway
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Bergen
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Poland
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Katowice
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Poland
State/province [84] 0 0
Warszawa
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Poland
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Wroclaw
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Portugal
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Braga
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Portugal
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Lisboa
Country [88] 0 0
Puerto Rico
State/province [88] 0 0
Ponce
Country [89] 0 0
Romania
State/province [89] 0 0
Timis
Country [90] 0 0
Romania
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Bucharest
Country [91] 0 0
Romania
State/province [91] 0 0
Constanta
Country [92] 0 0
Russian Federation
State/province [92] 0 0
Chelyabinsk
Country [93] 0 0
Russian Federation
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Izhevsk
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Russian Federation
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Krasnoyarsk
Country [95] 0 0
Russian Federation
State/province [95] 0 0
Moscow
Country [96] 0 0
Russian Federation
State/province [96] 0 0
Novosibirsk
Country [97] 0 0
Russian Federation
State/province [97] 0 0
Saint-Petersburg
Country [98] 0 0
Russian Federation
State/province [98] 0 0
Saratov
Country [99] 0 0
Russian Federation
State/province [99] 0 0
Tomsk
Country [100] 0 0
Serbia
State/province [100] 0 0
Belgrade
Country [101] 0 0
Serbia
State/province [101] 0 0
Nis
Country [102] 0 0
Serbia
State/province [102] 0 0
Novi Sad
Country [103] 0 0
Spain
State/province [103] 0 0
Leganés
Country [104] 0 0
Spain
State/province [104] 0 0
Madrid
Country [105] 0 0
Spain
State/province [105] 0 0
Vigo
Country [106] 0 0
Spain
State/province [106] 0 0
Vitoria
Country [107] 0 0
Sweden
State/province [107] 0 0
Göteborg
Country [108] 0 0
Sweden
State/province [108] 0 0
Huddinge
Country [109] 0 0
Sweden
State/province [109] 0 0
Uppsala
Country [110] 0 0
Taiwan
State/province [110] 0 0
Tainan city
Country [111] 0 0
Taiwan
State/province [111] 0 0
Taoyuan
Country [112] 0 0
Thailand
State/province [112] 0 0
Bangkok
Country [113] 0 0
Thailand
State/province [113] 0 0
Chiang Mai
Country [114] 0 0
Turkey
State/province [114] 0 0
Ankara
Country [115] 0 0
Turkey
State/province [115] 0 0
Istanbul
Country [116] 0 0
Turkey
State/province [116] 0 0
Kocaeli
Country [117] 0 0
United Kingdom
State/province [117] 0 0
Birmingham
Country [118] 0 0
United Kingdom
State/province [118] 0 0
London
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Manchester
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Norwich
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novo Nordisk A/S
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This trial is conducted globally. The aim of this trial is to assess the efficacy and safety
of liraglutide in the paediatric population in order to potentially address the unmet need
for treatment of children and adolescents with type 2 diabetes.
Trial website
https://clinicaltrials.gov/show/NCT01541215
Trial related presentations / publications
Tamborlane WV, Barrientos-Pérez M, Fainberg U, Frimer-Larsen H, Hafez M, Hale PM, Jalaludin MY, Kovarenko M, Libman I, Lynch JL, Rao P, Shehadeh N, Turan S, Weghuber D, Barrett T; Ellipse Trial Investigators. Liraglutide in Children and Adolescents with Type 2 Diabetes. N Engl J Med. 2019 Aug 15;381(7):637-646. doi: 10.1056/NEJMoa1903822. Epub 2019 Apr 28.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications