Metabolism and Nutrition Disorder, Obesity
Conditions
Brief summary
This trial is conducted globally. The aim of this trial is to investigate safety and efficacy of once-daily semaglutide in obese subjects without diabetes mellitus.
Interventions
DRUGsemaglutide
Once-daily subcutaneous (s.c., under the skin) administration with dose escalation.
DRUGliraglutide
Once-daily subcutaneous (s.c., under the skin) administration with dose escalation.
DRUGplacebo
Once-daily subcutaneous (s.c., under the skin) administration.
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 inform consent - Body mass index (BMI) equal or above 30.0 kg/m\^2 at the screening visit - At least one unsuccessful weight loss attempt per investigator judgement
Exclusion criteria
- A HbA1c (glycosylated haemoglobin) equal to or above 6.5% at screening or diagnosed with type 1 or type 2 diabetes mellitus - Treatment with glucose lowering agent(s) within 90 days before screening - Screening calcitonin equal to or above 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 - History of pancreatitis (acute or chronic) - Obesity induced by endocrine disorders (e.g. Cushing Syndrome) - Treatment with any medication within 90 days before screening that based on investigator's judgement may cause significant weight change - Previous surgical treatment for obesity (liposuction and/or abdominoplasty performed 1 year before screening is allowed) - History of major depressive disorder within 2 years before randomisation - Any lifetime history of a suicidal attempt - Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change in Body Weight (%) | Week 0, Week 52 | Relative change from baseline (week 0) in body weight was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline body weight as covariate. In-trial observation period was defined as the period from randomisation to last contact with trial site. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Weight Loss of ≥10% of Baseline Body Weight | Week 52 | Presented results are percentage of participants who lost more than or equal to 10% of their baseline (week 0) body weight at week 52. Analysis of observed in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using a binary logistic regression model with treatment, region and sex as factors and baseline body weight as covariate. In-trial observation period was defined as the period from randomisation to last contact with trial site. |
| Change in Body Weight (kg) | Week 0, Week 52 | Change from baseline (week 0) in body weight was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline body weight as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Change in Waist Circumference | Week 0, Week 52 | Change from baseline (week 0) in waist circumference was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline waist circumference as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Change in Waist to Hip Circumference Ratio | Week 0, Week 52 | Change from baseline (week 0) in waist to hip circumference ratio was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline waist to hip circumference ratio as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Change in BMI | Week 0, Week 52 | Change from baseline (week 0) in body mass index (BMI) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline BMI as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Change in HbA1c | Week 0, Week 52 | Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline HbA1c as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Change in FPG | Week 0, Week 52 | Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline FPG as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Change in Glycaemic Category (Normoglycaemia, Pre-diabetes, T2D) | Week 0, Week 52 | The categorisation of glycaemic status as described in the protocol was not aligned with the usual diagnosis criteria which require repeated testing of blood glucose to confirm the diagnosis and allows for the diagnosis to be made based on random glucose assessments and/or 2-hour glucose assessments during an oral glucose tolerance test. Therefore, data were not collected for this outcome measure. |
| Change in SBP | Week 0, Week 52 | Change from baseline (week 0) in systolic blood pressure (SBP) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline SBP as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Change in DBP | Week 0, Week 52 | Change from baseline (week 0) in diastolic blood pressure (DBP) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline DBP as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Week 0, Week 52 | Change from baseline (week 0) in lipids (total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL) cholesterol and triglycerides) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and respective baseline lipid value as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. Free fatty acid (FFA) results are not presented as the values were considered invalid. The shipment of the samples to be tested for FFA was not as per the requirement. |
| Change in hsCRP | Week 0, Week 52 | Change from baseline (week 0) in high-sensitivity C-reactive protein (hsCRP) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline hsCRP as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Change in IWQoL Lite | Week 0, Week 52 | The planned analyses of the Impact of Weight on Quality of Life Lite (IWQoL-Lite) for Clinical Trials scores were not performed. The measure was still under development, and Novo Nordisk had not obtained a validated scoring of the instrument by the time of analysis of the trial results. Therefore, the total and subdomain scores on the IWQoL-Lite could not be provided. |
| Change in SF-36 | Week 0, Week 52 | Short Form-36 (SF-36) is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at week 52. A positive change score indicates an improvement since baseline. Results are based on the in-trial observation period. |
| Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0, Week 52 | Participants' status on receiving concomitant medication (antihypertensive and lipid-lowering medications) at week 0 (yes/no) and week 52 (decreased, no change, increased or missing) are presented. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Compliance With Nutritional Counselling | Week 4-52 | This outcome measure presents nutritional compliance results recorded at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52. Nutritional compliance was recorded on a 0 to 10 numeric rating scale (NRS), with higher scores representing better compliance. |
| Number of AEs During the Trial | Week 0-59 | Adverse events (AEs) were recorded from week 0 to week 59. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Participants With Weight Loss of ≥5% of Baseline Body Weight | Week 52 | Presented results are percentage of participants who lost more than or equal to 5% of their baseline (week 0) body weight at week 52. Analysis of observed in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using a binary logistic regression model with treatment, region and sex as factors and baseline body weight as covariate. In-trial observation period was defined as the period from randomisation to last contact with trial site. |
| Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Week 0-59 | Presented results are the number of nausea, vomiting, diarrhoea, and constipation events recorded from week 0 to week 59. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Week 52 | This outcome measure presents results recorded at week 52. If a participant experienced an event of nausea within 24 hours prior to a site visit, a nausea questionnaire had to be completed. Participants experiencing such events were to answer 5 different categories in the questionnaire ('duration of nausea', 'time from the latest injection of trial product to the onset of nausea', 'time from last food intake to the onset of nausea', 'nausea accompanied by vomiting (yes/no)' and 'severity of nausea (worst during episode)'). Severity of nausea was recorded on a 0 to 10 numeric rating scale (NRS), where 0 = 'No nausea' and 10 = 'Nausea as bad as it could be'. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
| Change in ECG | Week 0, week 52 | Number of participants with electrocardiogram (ECG) results, normal; abnormal, not clinically significant (NCS) or abnormal, clinically significant (CS) was recorded at baseline (week 0) and week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Pulse | Week 0, week 52 | Change from baseline (week 0) in pulse rate was evaluated at week 52. Analysis of observed data using a mixed model for repeated measurements (MMRM) with treatment, region and sex as factors and baseline pulse as covariate, all nested within visit. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Haematology: Haemoglobin | Week 0, week 52 | Change from baseline (week 0) in haemoglobin was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Haematology: Haematocrit | Week 0, week 52 | Change from baseline (week 0) in haematocrit was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Week 0, week 52 | Change from baseline (week 0) in haematological parameters, thrombocytes, leucocytes and differential cell count (eosinophils, neutrophils, basophils, monocytes and lymphocytes) were evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Haematology: Erythrocytes | Week 0, week 52 | Change from baseline (week 0) in erythrocytes was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Biochemistry: Creatinine and Bilirubin (Total) | Week 0, week 52 | Change from baseline (week 0) in biochemistry parameters, creatinine and bilirubin (total) were evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Week 0, week 52 | Change from baseline (week 0) in biochemistry parameters, creatinine kinase, amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Week 0, week 52 | Change from baseline (week 0) in biochemistry parameters, urea, sodium, potassium and calcium (total) were evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Biochemistry: Albumin | Week 0, week 52 | Change from baseline (week 0) in albumin was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Biochemistry: Calcitonin | Week 0, week 52 | Change from baseline (week 0) in calcitonin was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Biochemistry: TSH | Week 0, week 52 | Change from baseline (week 0) in thyroid stimulating hormone (TSH) was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Mental Health Assessed by C-SSRS | Week 0 and Week 4-59 | Presented results are the number of participants with Columbia Suicidality Severity Rating Scale (C-SSRS) results recorded during baseline (week 0) and post baseline (week 4-52) visits. For classification of the events reported on the C-SSRS, the following categories were used: 1) Suicidal ideation, 2) Suicidal behaviour and 3) Non-suicidal self-injurious behaviour. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Change in Mental Health Assessed by PHQ-9 | Week 0, week 52 | Patient health questionnaire-9 (PHQ-9) was recorded at baseline (week 0) and week 52. The PHQ-9 questionnaire is a 9-item depression module included in the patient health questionnaire, a self-administered diagnostic tool used for assessment of mental disorders. On the PHQ-9, the participant rates the frequency of 9 items on a scale from 0 (not at all) to 3 (nearly every day). The PHQ-9 total score ranges from 0-27; total scores of 1-4 represent no depression, total scores of 5-9 represent mild depression, total scores of 10-14 represent moderate depression, total scores of 15-19 represent moderately severe depression and total scores of 20-27 represent severe depression. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration. |
| Anti-semaglutide Antibodies During and After Treatment | Week 0-52 | Participants were tested for anti-semaglutide antibodies from week 0 (post treatment) to week 52 (at weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52). This outcome measure is applicable only for the semaglutide treatment arms. |
| Number of Hypoglycaemic Episodes During the Trial | Week 0-59 | Hypoglycaemic episodes were identified by either: 1) Subject reporting of symptoms of hypoglycaemia (low blood sugar) or 2) fasting plasma glucose (FPG) values ≤3.9 mmol/L (70 mg/dL) from blood sampling at site visits. Hypoglycaemic episodes were recorded from week 0 to week 59. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. |
Countries
Australia, Belgium, Canada, Germany, Israel, Russia, United Kingdom, United States
Participant flow
Recruitment details
The trial was conducted at 71 sites in 8 countries as follows: Australia: 5, Belgium: 5, Canada: 9, Germany: 6, Israel: 7, Russian Federation: 10, United Kingdom (UK):8, United States (US): 21. Along with this, recruitment of participants was planned at 3 sites (1 each in Germany, Russian Federation, and US), but where no participants were screened
Pre-assignment details
Design:Participants were randomised to 1 of the 16 parallel treatment arms in a 6:1 ratio (active:placebo) to receive either:A)Semaglutide 0.05/0.1/0.2/0.3/0.4 mg; dose escalation every 4th week B)Semaglutide 0.3/0.4 mg; dose escalation every second week C)Liraglutide 3.0 mg;dose escalation every week D)Placebo;matching each of the active treatment
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide 0.05 mg Participants received once daily semaglutide 0.05 mg s.c. injections for 52 weeks. | 103 |
| Semaglutide 0.1 mg Participants received once daily semaglutide s.c. injections for 52 weeks. Dose escalation was done at every fourth week as following: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 52). | 102 |
| Semaglutide 0.2 mg Participants received once daily semaglutide s.c. injections for 52 weeks. Dose escalation was done at every fourth week as following: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), and 0.2 mg (week 9 to week 52). | 103 |
| Semaglutide 0.3 mg Participants received once daily semaglutide s.c. injections for 52 weeks. Dose escalation was done at every fourth week as following: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), and 0.3 mg (week 13 to week 52). | 103 |
| Semaglutide 0.4 mg Participants received once daily semaglutide s.c. injections for 52 weeks. Dose escalation was done at every fourth week as following: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16), and 0.4 mg (week 17 to week 52). | 102 |
| Semaglutide 0.3 mg (Fast Escalation) Participants received once daily semaglutide s.c. injections for 52 weeks. Dose escalation was done at every second week (fast escalation) as following: 0.05 mg (in weeks 1 and 2), 0.1 mg (in weeks 3 and 4), 0.2 mg (in weeks 5 and 6), and 0.3 mg (week 7 to week 52). | 102 |
| Semaglutide 0.4 mg (Fast Escalation) Participants received once daily semaglutide s.c. injections for 52 weeks. Dose escalation was done at every second week (fast escalation) as following: 0.05 mg (in weeks 1 and 2), 0.1 mg (in weeks 3 and 4), 0.2 mg (in weeks 5 and 6), 0.3 mg (in weeks 7 and 8), and 0.4 mg (week 9 to week 52). | 103 |
| Liraglutide 3.0 mg Participants received once daily liraglutide s.c. injections for 52 weeks. Dose escalation was done at every week as following: 0.6 mg in week 1, 1.2 mg in week 2, 1.8 mg in week 3, 2.4 mg in week 4, and 3.0 mg from week 5 to week 52. | 103 |
| Placebo Pool Participants received once daily placebo s.c injections (matching each of the active treatment arms: semaglutide 0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg (dose escalation every fourth week); semaglutide 0.3 mg or 0.4 mg (dose escalation every second week); liraglutide 3.0 mg (dose escalation every week)). | 136 |
| Total | 957 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 5 | 3 | 2 | 3 | 1 | 5 | 2 | 6 | 6 |
| Overall Study | Unclassified | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 4 | 6 | 4 | 1 | 1 | 0 | 1 | 7 |
Baseline characteristics
| Characteristic | Semaglutide 0.05 mg | Semaglutide 0.1 mg | Semaglutide 0.2 mg | Semaglutide 0.3 mg | Semaglutide 0.4 mg | Semaglutide 0.3 mg (Fast Escalation) | Semaglutide 0.4 mg (Fast Escalation) | Liraglutide 3.0 mg | Placebo Pool | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 46.97 Years STANDARD_DEVIATION 12.8 | 45.24 Years STANDARD_DEVIATION 12.62 | 44.37 Years STANDARD_DEVIATION 11.24 | 46.73 Years STANDARD_DEVIATION 12.02 | 48.37 Years STANDARD_DEVIATION 13.44 | 47.10 Years STANDARD_DEVIATION 12.05 | 46.07 Years STANDARD_DEVIATION 13.51 | 48.50 Years STANDARD_DEVIATION 11.22 | 46.42 Years STANDARD_DEVIATION 12.8 | 46.63 Years STANDARD_DEVIATION 12.46 |
| Body weight | 111.29 Kilogram (Kg) STANDARD_DEVIATION 23.17 | 111.31 Kilogram (Kg) STANDARD_DEVIATION 21.47 | 114.49 Kilogram (Kg) STANDARD_DEVIATION 24.53 | 111.51 Kilogram (Kg) STANDARD_DEVIATION 22.96 | 113.20 Kilogram (Kg) STANDARD_DEVIATION 26.42 | 108.11 Kilogram (Kg) STANDARD_DEVIATION 22.08 | 109.56 Kilogram (Kg) STANDARD_DEVIATION 21.33 | 108.71 Kilogram (Kg) STANDARD_DEVIATION 21.94 | 114.19 Kilogram (Kg) STANDARD_DEVIATION 25.37 | 111.48 Kilogram (Kg) STANDARD_DEVIATION 23.39 |
| Fasting plasma glucose (FPG) | 5.48 Millimoles per litre (mmol/L) STANDARD_DEVIATION 0.64 | 5.48 Millimoles per litre (mmol/L) STANDARD_DEVIATION 0.55 | 5.41 Millimoles per litre (mmol/L) STANDARD_DEVIATION 0.77 | 5.48 Millimoles per litre (mmol/L) STANDARD_DEVIATION 0.73 | 5.40 Millimoles per litre (mmol/L) STANDARD_DEVIATION 0.67 | 5.43 Millimoles per litre (mmol/L) STANDARD_DEVIATION 0.64 | 5.54 Millimoles per litre (mmol/L) STANDARD_DEVIATION 0.87 | 5.55 Millimoles per litre (mmol/L) STANDARD_DEVIATION 0.73 | 5.50 Millimoles per litre (mmol/L) STANDARD_DEVIATION 0.62 | 5.48 Millimoles per litre (mmol/L) STANDARD_DEVIATION 0.69 |
| Glycosylated haemoglobin (HbA1c) | 5.51 Percentage (%) of HbA1c STANDARD_DEVIATION 0.35 | 5.45 Percentage (%) of HbA1c STANDARD_DEVIATION 0.43 | 5.41 Percentage (%) of HbA1c STANDARD_DEVIATION 0.39 | 5.51 Percentage (%) of HbA1c STANDARD_DEVIATION 0.38 | 5.47 Percentage (%) of HbA1c STANDARD_DEVIATION 0.42 | 5.48 Percentage (%) of HbA1c STANDARD_DEVIATION 0.41 | 5.49 Percentage (%) of HbA1c STANDARD_DEVIATION 0.42 | 5.53 Percentage (%) of HbA1c STANDARD_DEVIATION 0.38 | 5.54 Percentage (%) of HbA1c STANDARD_DEVIATION 0.38 | 5.49 Percentage (%) of HbA1c STANDARD_DEVIATION 0.4 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 7 Participants | 10 Participants | 3 Participants | 10 Participants | 0 Participants | 7 Participants | 9 Participants | 10 Participants | 61 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants | 7 Participants | 6 Participants | 13 Participants | 4 Participants | 6 Participants | 3 Participants | 6 Participants | 7 Participants | 55 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Not applicable | 4 Participants | 9 Participants | 4 Participants | 11 Participants | 8 Participants | 14 Participants | 9 Participants | 4 Participants | 12 Participants | 75 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 96 Participants | 86 Participants | 93 Participants | 79 Participants | 90 Participants | 82 Participants | 91 Participants | 93 Participants | 117 Participants | 827 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 88 Participants | 76 Participants | 72 Participants | 74 Participants | 71 Participants | 76 Participants | 68 Participants | 78 Participants | 97 Participants | 700 Participants |
| Sex: Female, Male Female | 67 Participants | 66 Participants | 66 Participants | 66 Participants | 66 Participants | 66 Participants | 67 Participants | 67 Participants | 88 Participants | 619 Participants |
| Sex: Female, Male Male | 36 Participants | 36 Participants | 37 Participants | 37 Participants | 36 Participants | 36 Participants | 36 Participants | 36 Participants | 48 Participants | 338 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 103 | 0 / 102 | 0 / 103 | 0 / 103 | 0 / 102 | 0 / 102 | 1 / 103 | 0 / 103 | 0 / 136 |
| other Total, other adverse events | 83 / 103 | 87 / 102 | 84 / 103 | 85 / 103 | 90 / 102 | 91 / 102 | 88 / 103 | 83 / 103 | 87 / 136 |
| serious Total, serious adverse events | 13 / 103 | 8 / 102 | 5 / 103 | 6 / 103 | 13 / 102 | 6 / 102 | 7 / 103 | 4 / 103 | 11 / 136 |
Outcome results
Primary
Relative Change in Body Weight (%)
Relative change from baseline (week 0) in body weight was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline body weight as covariate. In-trial observation period was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Relative Change in Body Weight (%) | -5.99 Percentage (%) of body weight | Standard Error 0.85 |
| Semaglutide 0.1 mg | Relative Change in Body Weight (%) | -8.62 Percentage (%) of body weight | Standard Error 0.84 |
| Semaglutide 0.2 mg | Relative Change in Body Weight (%) | -11.60 Percentage (%) of body weight | Standard Error 0.85 |
| Semaglutide 0.3 mg | Relative Change in Body Weight (%) | -11.17 Percentage (%) of body weight | Standard Error 0.85 |
| Semaglutide 0.4 mg | Relative Change in Body Weight (%) | -13.84 Percentage (%) of body weight | Standard Error 0.83 |
| Semaglutide 0.3 mg (Fast Escalation) | Relative Change in Body Weight (%) | -11.38 Percentage (%) of body weight | Standard Error 0.85 |
| Semaglutide 0.4 mg (Fast Escalation) | Relative Change in Body Weight (%) | -16.29 Percentage (%) of body weight | Standard Error 0.83 |
| Liraglutide 3.0 mg | Relative Change in Body Weight (%) | -7.76 Percentage (%) of body weight | Standard Error 0.85 |
| Placebo Pool | Relative Change in Body Weight (%) | -2.29 Percentage (%) of body weight | Standard Error 0.74 |
Comparison: J2R-MI: Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline body weight as covariate. Dunnett's method was used to adjust for multiple comparisons.p-value: =0.005595% CI: [-6.55, -0.85]ANCOVA
Comparison: J2R-MI: Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline body weight as covariate. Dunnett's method was used to adjust for multiple comparisons.p-value: <0.000195% CI: [-9.16, -3.49]ANCOVA
Comparison: J2R-MI: Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline body weight as covariate. Dunnett's method was used to adjust for multiple comparisons.p-value: <0.000195% CI: [-12.15, -6.46]ANCOVA
Comparison: J2R-MI: Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline body weight as covariate. Dunnett's method was used to adjust for multiple comparisons.p-value: <0.000195% CI: [-11.72, -6.03]ANCOVA
Comparison: J2R-MI: Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline body weight as covariate. Dunnett's method was used to adjust for multiple comparisons.p-value: <0.000195% CI: [-14.38, -8.72]ANCOVA
Secondary
Anti-semaglutide Antibodies During and After Treatment
Participants were tested for anti-semaglutide antibodies from week 0 (post treatment) to week 52 (at weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52). This outcome measure is applicable only for the semaglutide treatment arms.
Time frame: Week 0-52
Population: Overall number of participants analyzed = SAS which included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide 0.05 mg | Anti-semaglutide Antibodies During and After Treatment | 0 Participants |
| Semaglutide 0.1 mg | Anti-semaglutide Antibodies During and After Treatment | 0 Participants |
| Semaglutide 0.2 mg | Anti-semaglutide Antibodies During and After Treatment | 0 Participants |
| Semaglutide 0.3 mg | Anti-semaglutide Antibodies During and After Treatment | 0 Participants |
| Semaglutide 0.4 mg | Anti-semaglutide Antibodies During and After Treatment | 0 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Anti-semaglutide Antibodies During and After Treatment | 0 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Anti-semaglutide Antibodies During and After Treatment | 0 Participants |
Secondary
Change in Biochemistry: Albumin
Change from baseline (week 0) in albumin was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = number of participants in the SAS with available data. SAS included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in Biochemistry: Albumin | 0.03 Gram/decilitre (g/dL) | Standard Deviation 0.18 |
| Semaglutide 0.1 mg | Change in Biochemistry: Albumin | 0.01 Gram/decilitre (g/dL) | Standard Deviation 0.21 |
| Semaglutide 0.2 mg | Change in Biochemistry: Albumin | 0.07 Gram/decilitre (g/dL) | Standard Deviation 0.2 |
| Semaglutide 0.3 mg | Change in Biochemistry: Albumin | 0.05 Gram/decilitre (g/dL) | Standard Deviation 0.21 |
| Semaglutide 0.4 mg | Change in Biochemistry: Albumin | 0.03 Gram/decilitre (g/dL) | Standard Deviation 0.22 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Albumin | 0.01 Gram/decilitre (g/dL) | Standard Deviation 0.21 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Albumin | 0.02 Gram/decilitre (g/dL) | Standard Deviation 0.23 |
| Liraglutide 3.0 mg | Change in Biochemistry: Albumin | 0.06 Gram/decilitre (g/dL) | Standard Deviation 0.18 |
| Placebo Pool | Change in Biochemistry: Albumin | 0.04 Gram/decilitre (g/dL) | Standard Deviation 0.2 |
Secondary
Change in Biochemistry: Calcitonin
Change from baseline (week 0) in calcitonin was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = number of female participants in the SAS with available data. SAS included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in Biochemistry: Calcitonin | 0.08 Nanogram/litre (ng/L) | Standard Deviation 0.71 |
| Semaglutide 0.1 mg | Change in Biochemistry: Calcitonin | 0.03 Nanogram/litre (ng/L) | Standard Deviation 1.07 |
| Semaglutide 0.2 mg | Change in Biochemistry: Calcitonin | 0.04 Nanogram/litre (ng/L) | Standard Deviation 0.44 |
| Semaglutide 0.3 mg | Change in Biochemistry: Calcitonin | 0.04 Nanogram/litre (ng/L) | Standard Deviation 0.18 |
| Semaglutide 0.4 mg | Change in Biochemistry: Calcitonin | 0.17 Nanogram/litre (ng/L) | Standard Deviation 0.79 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Calcitonin | -0.01 Nanogram/litre (ng/L) | Standard Deviation 0.73 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Calcitonin | 0.20 Nanogram/litre (ng/L) | Standard Deviation 0.72 |
| Liraglutide 3.0 mg | Change in Biochemistry: Calcitonin | 0.29 Nanogram/litre (ng/L) | Standard Deviation 1.27 |
| Placebo Pool | Change in Biochemistry: Calcitonin | -0.12 Nanogram/litre (ng/L) | Standard Deviation 2.16 |
Secondary
Change in Biochemistry: Creatinine and Bilirubin (Total)
Change from baseline (week 0) in biochemistry parameters, creatinine and bilirubin (total) were evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = SAS which included all participants receiving at least one dose of the randomised treatment. Number Analyzed = number of participants in the SAS with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 0.05 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Creatinine | -1.14 Micromole/litre (umol/L) | Standard Deviation 6.53 |
| Semaglutide 0.05 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Bilirubin (total) | 0.30 Micromole/litre (umol/L) | Standard Deviation 3.7 |
| Semaglutide 0.1 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Creatinine | -0.85 Micromole/litre (umol/L) | Standard Deviation 7.59 |
| Semaglutide 0.1 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Bilirubin (total) | 1.12 Micromole/litre (umol/L) | Standard Deviation 3.6 |
| Semaglutide 0.2 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Creatinine | -1.09 Micromole/litre (umol/L) | Standard Deviation 6.11 |
| Semaglutide 0.2 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Bilirubin (total) | 1.59 Micromole/litre (umol/L) | Standard Deviation 3.11 |
| Semaglutide 0.3 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Creatinine | 0.76 Micromole/litre (umol/L) | Standard Deviation 8.11 |
| Semaglutide 0.3 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Bilirubin (total) | 1.33 Micromole/litre (umol/L) | Standard Deviation 3.61 |
| Semaglutide 0.4 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Creatinine | 1.48 Micromole/litre (umol/L) | Standard Deviation 29.73 |
| Semaglutide 0.4 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Bilirubin (total) | 1.23 Micromole/litre (umol/L) | Standard Deviation 5.18 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Creatinine and Bilirubin (Total) | Bilirubin (total) | 1.02 Micromole/litre (umol/L) | Standard Deviation 4.04 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Creatinine and Bilirubin (Total) | Creatinine | 1.05 Micromole/litre (umol/L) | Standard Deviation 8.45 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Creatinine and Bilirubin (Total) | Bilirubin (total) | 1.67 Micromole/litre (umol/L) | Standard Deviation 4.28 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Creatinine and Bilirubin (Total) | Creatinine | -2.10 Micromole/litre (umol/L) | Standard Deviation 8.49 |
| Liraglutide 3.0 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Creatinine | -0.81 Micromole/litre (umol/L) | Standard Deviation 7.16 |
| Liraglutide 3.0 mg | Change in Biochemistry: Creatinine and Bilirubin (Total) | Bilirubin (total) | 1.02 Micromole/litre (umol/L) | Standard Deviation 3.67 |
| Placebo Pool | Change in Biochemistry: Creatinine and Bilirubin (Total) | Creatinine | 0.28 Micromole/litre (umol/L) | Standard Deviation 8.06 |
| Placebo Pool | Change in Biochemistry: Creatinine and Bilirubin (Total) | Bilirubin (total) | 1.09 Micromole/litre (umol/L) | Standard Deviation 4.45 |
Secondary
Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP
Change from baseline (week 0) in biochemistry parameters, creatinine kinase, amylase, lipase, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = SAS which included all participants receiving at least one dose of the randomised treatment. Number Analyzed = number of participants in the SAS with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 0.05 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALT | -5.82 Unit/litre (U/L) | Standard Deviation 20.97 |
| Semaglutide 0.05 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Amylase | 3.35 Unit/litre (U/L) | Standard Deviation 13.82 |
| Semaglutide 0.05 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | AST | -1.08 Unit/litre (U/L) | Standard Deviation 12.17 |
| Semaglutide 0.05 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALP | -3.42 Unit/litre (U/L) | Standard Deviation 13.04 |
| Semaglutide 0.05 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Lipase | 5.62 Unit/litre (U/L) | Standard Deviation 32.22 |
| Semaglutide 0.05 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Creatinine kinase | 0.53 Unit/litre (U/L) | Standard Deviation 68.43 |
| Semaglutide 0.1 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | AST | -1.99 Unit/litre (U/L) | Standard Deviation 7.95 |
| Semaglutide 0.1 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALP | -3.44 Unit/litre (U/L) | Standard Deviation 16 |
| Semaglutide 0.1 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Creatinine kinase | -44.75 Unit/litre (U/L) | Standard Deviation 266.88 |
| Semaglutide 0.1 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Lipase | 8.83 Unit/litre (U/L) | Standard Deviation 28.1 |
| Semaglutide 0.1 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Amylase | 4.84 Unit/litre (U/L) | Standard Deviation 13.05 |
| Semaglutide 0.1 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALT | -5.45 Unit/litre (U/L) | Standard Deviation 12.64 |
| Semaglutide 0.2 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | AST | -2.33 Unit/litre (U/L) | Standard Deviation 7.61 |
| Semaglutide 0.2 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Creatinine kinase | -13.20 Unit/litre (U/L) | Standard Deviation 44.33 |
| Semaglutide 0.2 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Amylase | 9.20 Unit/litre (U/L) | Standard Deviation 12.72 |
| Semaglutide 0.2 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALP | -6.21 Unit/litre (U/L) | Standard Deviation 10.96 |
| Semaglutide 0.2 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALT | -7.44 Unit/litre (U/L) | Standard Deviation 17.14 |
| Semaglutide 0.2 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Lipase | 17.55 Unit/litre (U/L) | Standard Deviation 41.2 |
| Semaglutide 0.3 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALP | -6.70 Unit/litre (U/L) | Standard Deviation 13.89 |
| Semaglutide 0.3 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Creatinine kinase | -46.34 Unit/litre (U/L) | Standard Deviation 163.09 |
| Semaglutide 0.3 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALT | -9.15 Unit/litre (U/L) | Standard Deviation 23.09 |
| Semaglutide 0.3 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Lipase | 13.28 Unit/litre (U/L) | Standard Deviation 34.86 |
| Semaglutide 0.3 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | AST | -3.32 Unit/litre (U/L) | Standard Deviation 10.22 |
| Semaglutide 0.3 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Amylase | 7.53 Unit/litre (U/L) | Standard Deviation 13.94 |
| Semaglutide 0.4 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Lipase | 13.33 Unit/litre (U/L) | Standard Deviation 17.92 |
| Semaglutide 0.4 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Creatinine kinase | -29.91 Unit/litre (U/L) | Standard Deviation 95.05 |
| Semaglutide 0.4 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Amylase | 7.67 Unit/litre (U/L) | Standard Deviation 16.26 |
| Semaglutide 0.4 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALT | -3.64 Unit/litre (U/L) | Standard Deviation 11.3 |
| Semaglutide 0.4 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | AST | -2.07 Unit/litre (U/L) | Standard Deviation 6.7 |
| Semaglutide 0.4 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALP | -4.25 Unit/litre (U/L) | Standard Deviation 12.65 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Creatinine kinase | -8.86 Unit/litre (U/L) | Standard Deviation 47.28 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Amylase | 8.39 Unit/litre (U/L) | Standard Deviation 20.28 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | AST | -1.62 Unit/litre (U/L) | Standard Deviation 10.78 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALT | -9.07 Unit/litre (U/L) | Standard Deviation 20.96 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Lipase | 14.92 Unit/litre (U/L) | Standard Deviation 44.31 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALP | -3.50 Unit/litre (U/L) | Standard Deviation 15.61 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Creatinine kinase | -28.08 Unit/litre (U/L) | Standard Deviation 122.61 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Lipase | 15.09 Unit/litre (U/L) | Standard Deviation 36.28 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Amylase | 7.78 Unit/litre (U/L) | Standard Deviation 14.82 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | AST | -2.73 Unit/litre (U/L) | Standard Deviation 6.1 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALP | -8.20 Unit/litre (U/L) | Standard Deviation 14.13 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALT | -7.17 Unit/litre (U/L) | Standard Deviation 12.62 |
| Liraglutide 3.0 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Lipase | 11.86 Unit/litre (U/L) | Standard Deviation 27.48 |
| Liraglutide 3.0 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Amylase | 7.12 Unit/litre (U/L) | Standard Deviation 15.72 |
| Liraglutide 3.0 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALT | -2.95 Unit/litre (U/L) | Standard Deviation 14.19 |
| Liraglutide 3.0 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Creatinine kinase | -3.09 Unit/litre (U/L) | Standard Deviation 172.46 |
| Liraglutide 3.0 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALP | -0.52 Unit/litre (U/L) | Standard Deviation 9.8 |
| Liraglutide 3.0 mg | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | AST | -1.48 Unit/litre (U/L) | Standard Deviation 10.13 |
| Placebo Pool | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | AST | 0.00 Unit/litre (U/L) | Standard Deviation 11.08 |
| Placebo Pool | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALP | -1.46 Unit/litre (U/L) | Standard Deviation 11.39 |
| Placebo Pool | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Creatinine kinase | 53.36 Unit/litre (U/L) | Standard Deviation 571.63 |
| Placebo Pool | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | ALT | -3.03 Unit/litre (U/L) | Standard Deviation 11.91 |
| Placebo Pool | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Amylase | 3.41 Unit/litre (U/L) | Standard Deviation 12.27 |
| Placebo Pool | Change in Biochemistry: Creatinine Kinase, Amylase, Lipase, ALT, AST and ALP | Lipase | 1.63 Unit/litre (U/L) | Standard Deviation 11.57 |
Secondary
Change in Biochemistry: TSH
Change from baseline (week 0) in thyroid stimulating hormone (TSH) was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = number of participants in the SAS with available data. SAS included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in Biochemistry: TSH | -0.31 Milli-international units/litre (mIU/L) | Standard Deviation 1.62 |
| Semaglutide 0.1 mg | Change in Biochemistry: TSH | -0.10 Milli-international units/litre (mIU/L) | Standard Deviation 1.1 |
| Semaglutide 0.2 mg | Change in Biochemistry: TSH | -0.22 Milli-international units/litre (mIU/L) | Standard Deviation 0.85 |
| Semaglutide 0.3 mg | Change in Biochemistry: TSH | -0.18 Milli-international units/litre (mIU/L) | Standard Deviation 1.04 |
| Semaglutide 0.4 mg | Change in Biochemistry: TSH | -0.10 Milli-international units/litre (mIU/L) | Standard Deviation 0.96 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: TSH | -0.12 Milli-international units/litre (mIU/L) | Standard Deviation 0.84 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: TSH | -0.43 Milli-international units/litre (mIU/L) | Standard Deviation 1.01 |
| Liraglutide 3.0 mg | Change in Biochemistry: TSH | 0.02 Milli-international units/litre (mIU/L) | Standard Deviation 0.88 |
| Placebo Pool | Change in Biochemistry: TSH | -0.07 Milli-international units/litre (mIU/L) | Standard Deviation 0.97 |
Secondary
Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total)
Change from baseline (week 0) in biochemistry parameters, urea, sodium, potassium and calcium (total) were evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = SAS which included all participants receiving at least one dose of the randomised treatment. Number Analyzed = number of participants in the SAS with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 0.05 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Urea | -0.04 Millimole/litre (mmol/L) | Standard Deviation 1.06 |
| Semaglutide 0.05 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Sodium | -0.18 Millimole/litre (mmol/L) | Standard Deviation 2.47 |
| Semaglutide 0.05 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Potassium | 0.01 Millimole/litre (mmol/L) | Standard Deviation 0.3 |
| Semaglutide 0.05 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Calcium (total) | 0.01 Millimole/litre (mmol/L) | Standard Deviation 0.07 |
| Semaglutide 0.1 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Calcium (total) | -0.01 Millimole/litre (mmol/L) | Standard Deviation 0.09 |
| Semaglutide 0.1 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Urea | 0.16 Millimole/litre (mmol/L) | Standard Deviation 1.26 |
| Semaglutide 0.1 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Sodium | -0.27 Millimole/litre (mmol/L) | Standard Deviation 1.77 |
| Semaglutide 0.1 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Potassium | 0.01 Millimole/litre (mmol/L) | Standard Deviation 0.38 |
| Semaglutide 0.2 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Sodium | -0.40 Millimole/litre (mmol/L) | Standard Deviation 2.41 |
| Semaglutide 0.2 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Calcium (total) | 0.01 Millimole/litre (mmol/L) | Standard Deviation 0.08 |
| Semaglutide 0.2 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Potassium | -0.00 Millimole/litre (mmol/L) | Standard Deviation 0.31 |
| Semaglutide 0.2 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Urea | -0.01 Millimole/litre (mmol/L) | Standard Deviation 1.21 |
| Semaglutide 0.3 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Urea | -0.10 Millimole/litre (mmol/L) | Standard Deviation 1.25 |
| Semaglutide 0.3 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Sodium | -0.82 Millimole/litre (mmol/L) | Standard Deviation 2.36 |
| Semaglutide 0.3 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Potassium | -0.04 Millimole/litre (mmol/L) | Standard Deviation 0.36 |
| Semaglutide 0.3 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Calcium (total) | 0.01 Millimole/litre (mmol/L) | Standard Deviation 0.08 |
| Semaglutide 0.4 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Potassium | -0.10 Millimole/litre (mmol/L) | Standard Deviation 0.41 |
| Semaglutide 0.4 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Sodium | -0.92 Millimole/litre (mmol/L) | Standard Deviation 2.62 |
| Semaglutide 0.4 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Urea | -0.00 Millimole/litre (mmol/L) | Standard Deviation 1.88 |
| Semaglutide 0.4 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Calcium (total) | 0.00 Millimole/litre (mmol/L) | Standard Deviation 0.09 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Calcium (total) | -0.00 Millimole/litre (mmol/L) | Standard Deviation 0.08 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Urea | -0.06 Millimole/litre (mmol/L) | Standard Deviation 1.33 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Potassium | 0.00 Millimole/litre (mmol/L) | Standard Deviation 0.36 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Sodium | -0.76 Millimole/litre (mmol/L) | Standard Deviation 3.49 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Potassium | -0.11 Millimole/litre (mmol/L) | Standard Deviation 0.44 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Sodium | -0.74 Millimole/litre (mmol/L) | Standard Deviation 2.71 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Calcium (total) | 0.00 Millimole/litre (mmol/L) | Standard Deviation 0.09 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Urea | -0.33 Millimole/litre (mmol/L) | Standard Deviation 1.12 |
| Liraglutide 3.0 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Sodium | -0.37 Millimole/litre (mmol/L) | Standard Deviation 2.08 |
| Liraglutide 3.0 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Calcium (total) | 0.02 Millimole/litre (mmol/L) | Standard Deviation 0.08 |
| Liraglutide 3.0 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Potassium | -0.02 Millimole/litre (mmol/L) | Standard Deviation 0.35 |
| Liraglutide 3.0 mg | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Urea | 0.03 Millimole/litre (mmol/L) | Standard Deviation 1.06 |
| Placebo Pool | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Urea | 0.21 Millimole/litre (mmol/L) | Standard Deviation 1.21 |
| Placebo Pool | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Calcium (total) | -0.00 Millimole/litre (mmol/L) | Standard Deviation 0.08 |
| Placebo Pool | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Potassium | -0.04 Millimole/litre (mmol/L) | Standard Deviation 0.36 |
| Placebo Pool | Change in Biochemistry: Urea, Sodium, Potassium and Calcium (Total) | Sodium | -0.35 Millimole/litre (mmol/L) | Standard Deviation 2.08 |
Secondary
Change in BMI
Change from baseline (week 0) in body mass index (BMI) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline BMI as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in BMI | -2.37 Kilogram per square meter (kg/m^2) | Standard Error 0.33 |
| Semaglutide 0.1 mg | Change in BMI | -3.36 Kilogram per square meter (kg/m^2) | Standard Error 0.33 |
| Semaglutide 0.2 mg | Change in BMI | -4.38 Kilogram per square meter (kg/m^2) | Standard Error 0.33 |
| Semaglutide 0.3 mg | Change in BMI | -4.40 Kilogram per square meter (kg/m^2) | Standard Error 0.33 |
| Semaglutide 0.4 mg | Change in BMI | -5.40 Kilogram per square meter (kg/m^2) | Standard Error 0.33 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in BMI | -4.48 Kilogram per square meter (kg/m^2) | Standard Error 0.33 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in BMI | -6.21 Kilogram per square meter (kg/m^2) | Standard Error 0.33 |
| Liraglutide 3.0 mg | Change in BMI | -3.03 Kilogram per square meter (kg/m^2) | Standard Error 0.33 |
| Placebo Pool | Change in BMI | -0.88 Kilogram per square meter (kg/m^2) | Standard Error 0.29 |
Secondary
Change in Body Weight (kg)
Change from baseline (week 0) in body weight was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline body weight as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in Body Weight (kg) | -6.66 Kilogram (kg) | Standard Error 0.94 |
| Semaglutide 0.1 mg | Change in Body Weight (kg) | -9.34 Kilogram (kg) | Standard Error 0.93 |
| Semaglutide 0.2 mg | Change in Body Weight (kg) | -12.30 Kilogram (kg) | Standard Error 0.93 |
| Semaglutide 0.3 mg | Change in Body Weight (kg) | -12.45 Kilogram (kg) | Standard Error 0.93 |
| Semaglutide 0.4 mg | Change in Body Weight (kg) | -15.15 Kilogram (kg) | Standard Error 0.92 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Body Weight (kg) | -12.54 Kilogram (kg) | Standard Error 0.93 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Body Weight (kg) | -17.36 Kilogram (kg) | Standard Error 0.92 |
| Liraglutide 3.0 mg | Change in Body Weight (kg) | -8.47 Kilogram (kg) | Standard Error 0.93 |
| Placebo Pool | Change in Body Weight (kg) | -2.48 Kilogram (kg) | Standard Error 0.82 |
Secondary
Change in DBP
Change from baseline (week 0) in diastolic blood pressure (DBP) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline DBP as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in DBP | -2.55 Millimeters of mercury (mmHg) | Standard Error 0.84 |
| Semaglutide 0.1 mg | Change in DBP | -2.65 Millimeters of mercury (mmHg) | Standard Error 0.82 |
| Semaglutide 0.2 mg | Change in DBP | -4.09 Millimeters of mercury (mmHg) | Standard Error 0.83 |
| Semaglutide 0.3 mg | Change in DBP | -2.98 Millimeters of mercury (mmHg) | Standard Error 0.83 |
| Semaglutide 0.4 mg | Change in DBP | -3.61 Millimeters of mercury (mmHg) | Standard Error 0.8 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in DBP | -2.20 Millimeters of mercury (mmHg) | Standard Error 0.83 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in DBP | -5.52 Millimeters of mercury (mmHg) | Standard Error 0.8 |
| Liraglutide 3.0 mg | Change in DBP | -2.70 Millimeters of mercury (mmHg) | Standard Error 0.82 |
| Placebo Pool | Change in DBP | -1.50 Millimeters of mercury (mmHg) | Standard Error 0.73 |
Secondary
Change in ECG
Number of participants with electrocardiogram (ECG) results, normal; abnormal, not clinically significant (NCS) or abnormal, clinically significant (CS) was recorded at baseline (week 0) and week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = SAS which included all participants receiving at least one dose of the randomised treatment. Number Analyzed = number of participants in the SAS with available data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Semaglutide 0.05 mg | Change in ECG | Week: 0 | Normal | 70 Participants |
| Semaglutide 0.05 mg | Change in ECG | Week: 0 | Abnormal, NCS | 33 Participants |
| Semaglutide 0.05 mg | Change in ECG | Week: 52 | Abnormal, NCS | 25 Participants |
| Semaglutide 0.05 mg | Change in ECG | Week: 52 | Normal | 57 Participants |
| Semaglutide 0.05 mg | Change in ECG | Week: 0 | Abnormal, CS | 0 Participants |
| Semaglutide 0.05 mg | Change in ECG | Week: 52 | Abnormal, CS | 0 Participants |
| Semaglutide 0.1 mg | Change in ECG | Week: 0 | Abnormal, NCS | 31 Participants |
| Semaglutide 0.1 mg | Change in ECG | Week: 52 | Abnormal, CS | 0 Participants |
| Semaglutide 0.1 mg | Change in ECG | Week: 52 | Abnormal, NCS | 18 Participants |
| Semaglutide 0.1 mg | Change in ECG | Week: 0 | Normal | 69 Participants |
| Semaglutide 0.1 mg | Change in ECG | Week: 52 | Normal | 73 Participants |
| Semaglutide 0.1 mg | Change in ECG | Week: 0 | Abnormal, CS | 2 Participants |
| Semaglutide 0.2 mg | Change in ECG | Week: 0 | Normal | 74 Participants |
| Semaglutide 0.2 mg | Change in ECG | Week: 0 | Abnormal, NCS | 29 Participants |
| Semaglutide 0.2 mg | Change in ECG | Week: 52 | Abnormal, CS | 2 Participants |
| Semaglutide 0.2 mg | Change in ECG | Week: 52 | Normal | 67 Participants |
| Semaglutide 0.2 mg | Change in ECG | Week: 52 | Abnormal, NCS | 18 Participants |
| Semaglutide 0.2 mg | Change in ECG | Week: 0 | Abnormal, CS | 0 Participants |
| Semaglutide 0.3 mg | Change in ECG | Week: 0 | Normal | 62 Participants |
| Semaglutide 0.3 mg | Change in ECG | Week: 0 | Abnormal, NCS | 41 Participants |
| Semaglutide 0.3 mg | Change in ECG | Week: 0 | Abnormal, CS | 0 Participants |
| Semaglutide 0.3 mg | Change in ECG | Week: 52 | Normal | 58 Participants |
| Semaglutide 0.3 mg | Change in ECG | Week: 52 | Abnormal, NCS | 31 Participants |
| Semaglutide 0.3 mg | Change in ECG | Week: 52 | Abnormal, CS | 0 Participants |
| Semaglutide 0.4 mg | Change in ECG | Week: 0 | Abnormal, CS | 2 Participants |
| Semaglutide 0.4 mg | Change in ECG | Week: 0 | Abnormal, NCS | 38 Participants |
| Semaglutide 0.4 mg | Change in ECG | Week: 52 | Abnormal, CS | 1 Participants |
| Semaglutide 0.4 mg | Change in ECG | Week: 0 | Normal | 62 Participants |
| Semaglutide 0.4 mg | Change in ECG | Week: 52 | Normal | 57 Participants |
| Semaglutide 0.4 mg | Change in ECG | Week: 52 | Abnormal, NCS | 29 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in ECG | Week: 52 | Abnormal, NCS | 21 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in ECG | Week: 52 | Abnormal, CS | 1 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in ECG | Week: 0 | Abnormal, CS | 0 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in ECG | Week: 52 | Normal | 55 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in ECG | Week: 0 | Abnormal, NCS | 32 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in ECG | Week: 0 | Normal | 70 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in ECG | Week: 52 | Normal | 64 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in ECG | Week: 0 | Normal | 74 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in ECG | Week: 52 | Abnormal, CS | 0 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in ECG | Week: 0 | Abnormal, CS | 2 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in ECG | Week: 52 | Abnormal, NCS | 28 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in ECG | Week: 0 | Abnormal, NCS | 27 Participants |
| Liraglutide 3.0 mg | Change in ECG | Week: 52 | Normal | 59 Participants |
| Liraglutide 3.0 mg | Change in ECG | Week: 0 | Abnormal, NCS | 35 Participants |
| Liraglutide 3.0 mg | Change in ECG | Week: 52 | Abnormal, NCS | 26 Participants |
| Liraglutide 3.0 mg | Change in ECG | Week: 0 | Abnormal, CS | 0 Participants |
| Liraglutide 3.0 mg | Change in ECG | Week: 0 | Normal | 68 Participants |
| Liraglutide 3.0 mg | Change in ECG | Week: 52 | Abnormal, CS | 1 Participants |
| Placebo Pool | Change in ECG | Week: 52 | Normal | 66 Participants |
| Placebo Pool | Change in ECG | Week: 52 | Abnormal, CS | 0 Participants |
| Placebo Pool | Change in ECG | Week: 0 | Normal | 85 Participants |
| Placebo Pool | Change in ECG | Week: 52 | Abnormal, NCS | 40 Participants |
| Placebo Pool | Change in ECG | Week: 0 | Abnormal, CS | 0 Participants |
| Placebo Pool | Change in ECG | Week: 0 | Abnormal, NCS | 51 Participants |
Secondary
Change in FPG
Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline FPG as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in FPG | -0.29 Millimoles per litre (mmol/L) | Standard Error 0.06 |
| Semaglutide 0.1 mg | Change in FPG | -0.35 Millimoles per litre (mmol/L) | Standard Error 0.06 |
| Semaglutide 0.2 mg | Change in FPG | -0.40 Millimoles per litre (mmol/L) | Standard Error 0.06 |
| Semaglutide 0.3 mg | Change in FPG | -0.39 Millimoles per litre (mmol/L) | Standard Error 0.06 |
| Semaglutide 0.4 mg | Change in FPG | -0.43 Millimoles per litre (mmol/L) | Standard Error 0.06 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in FPG | -0.38 Millimoles per litre (mmol/L) | Standard Error 0.06 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in FPG | -0.51 Millimoles per litre (mmol/L) | Standard Error 0.06 |
| Liraglutide 3.0 mg | Change in FPG | -0.35 Millimoles per litre (mmol/L) | Standard Error 0.06 |
| Placebo Pool | Change in FPG | 0.01 Millimoles per litre (mmol/L) | Standard Error 0.05 |
Secondary
Change in Glycaemic Category (Normoglycaemia, Pre-diabetes, T2D)
The categorisation of glycaemic status as described in the protocol was not aligned with the usual diagnosis criteria which require repeated testing of blood glucose to confirm the diagnosis and allows for the diagnosis to be made based on random glucose assessments and/or 2-hour glucose assessments during an oral glucose tolerance test. Therefore, data were not collected for this outcome measure.
Time frame: Week 0, Week 52
Population: Data were not collected for this outcome measure.
Secondary
Change in Haematology: Erythrocytes
Change from baseline (week 0) in erythrocytes was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = number of participants in the SAS with available data. SAS included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in Haematology: Erythrocytes | -0.01 10^12 cells/litre (L) | Standard Deviation 0.26 |
| Semaglutide 0.1 mg | Change in Haematology: Erythrocytes | -0.06 10^12 cells/litre (L) | Standard Deviation 0.35 |
| Semaglutide 0.2 mg | Change in Haematology: Erythrocytes | -0.03 10^12 cells/litre (L) | Standard Deviation 0.27 |
| Semaglutide 0.3 mg | Change in Haematology: Erythrocytes | -0.04 10^12 cells/litre (L) | Standard Deviation 0.25 |
| Semaglutide 0.4 mg | Change in Haematology: Erythrocytes | -0.01 10^12 cells/litre (L) | Standard Deviation 0.29 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Haematology: Erythrocytes | -0.04 10^12 cells/litre (L) | Standard Deviation 0.24 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Haematology: Erythrocytes | -0.01 10^12 cells/litre (L) | Standard Deviation 0.27 |
| Liraglutide 3.0 mg | Change in Haematology: Erythrocytes | 0.05 10^12 cells/litre (L) | Standard Deviation 0.3 |
| Placebo Pool | Change in Haematology: Erythrocytes | 0.04 10^12 cells/litre (L) | Standard Deviation 0.24 |
Secondary
Change in Haematology: Haematocrit
Change from baseline (week 0) in haematocrit was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = number of participants in the SAS with available data. SAS included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in Haematology: Haematocrit | -0.25 Percentage of red blood cells | Standard Deviation 2.48 |
| Semaglutide 0.1 mg | Change in Haematology: Haematocrit | -0.58 Percentage of red blood cells | Standard Deviation 3.28 |
| Semaglutide 0.2 mg | Change in Haematology: Haematocrit | -0.42 Percentage of red blood cells | Standard Deviation 2.26 |
| Semaglutide 0.3 mg | Change in Haematology: Haematocrit | -0.49 Percentage of red blood cells | Standard Deviation 2.67 |
| Semaglutide 0.4 mg | Change in Haematology: Haematocrit | -0.31 Percentage of red blood cells | Standard Deviation 2.75 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Haematology: Haematocrit | -0.68 Percentage of red blood cells | Standard Deviation 2.82 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Haematology: Haematocrit | -0.15 Percentage of red blood cells | Standard Deviation 2.67 |
| Liraglutide 3.0 mg | Change in Haematology: Haematocrit | 0.26 Percentage of red blood cells | Standard Deviation 2.7 |
| Placebo Pool | Change in Haematology: Haematocrit | 0.26 Percentage of red blood cells | Standard Deviation 2.44 |
Secondary
Change in Haematology: Haemoglobin
Change from baseline (week 0) in haemoglobin was evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = number of participants in the SAS with available data. SAS included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in Haematology: Haemoglobin | 0.01 Millimoles per litre (mmol/L) | Standard Deviation 0.48 |
| Semaglutide 0.1 mg | Change in Haematology: Haemoglobin | -0.08 Millimoles per litre (mmol/L) | Standard Deviation 0.65 |
| Semaglutide 0.2 mg | Change in Haematology: Haemoglobin | -0.02 Millimoles per litre (mmol/L) | Standard Deviation 0.47 |
| Semaglutide 0.3 mg | Change in Haematology: Haemoglobin | -0.07 Millimoles per litre (mmol/L) | Standard Deviation 0.51 |
| Semaglutide 0.4 mg | Change in Haematology: Haemoglobin | 0.00 Millimoles per litre (mmol/L) | Standard Deviation 0.5 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Haematology: Haemoglobin | -0.07 Millimoles per litre (mmol/L) | Standard Deviation 0.47 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Haematology: Haemoglobin | 0.02 Millimoles per litre (mmol/L) | Standard Deviation 0.47 |
| Liraglutide 3.0 mg | Change in Haematology: Haemoglobin | 0.11 Millimoles per litre (mmol/L) | Standard Deviation 0.48 |
| Placebo Pool | Change in Haematology: Haemoglobin | -0.01 Millimoles per litre (mmol/L) | Standard Deviation 0.45 |
Secondary
Change in Haematology: Thrombocytes, Leucocytes and Differential Count
Change from baseline (week 0) in haematological parameters, thrombocytes, leucocytes and differential cell count (eosinophils, neutrophils, basophils, monocytes and lymphocytes) were evaluated at week 52. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = SAS which included all participants receiving at least one dose of the randomised treatment. Number Analyzed = number of participants in the SAS with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 0.05 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Lymphocytes | -0.10 10^9 cells/litre (L) | Standard Deviation 0.36 |
| Semaglutide 0.05 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Monocytes | -0.04 10^9 cells/litre (L) | Standard Deviation 0.18 |
| Semaglutide 0.05 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Neutrophils | -0.36 10^9 cells/litre (L) | Standard Deviation 1.17 |
| Semaglutide 0.05 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Leucocytes | -0.47 10^9 cells/litre (L) | Standard Deviation 1.38 |
| Semaglutide 0.05 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Thrombocytes | -2.08 10^9 cells/litre (L) | Standard Deviation 35.26 |
| Semaglutide 0.05 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Basophils | 0.00 10^9 cells/litre (L) | Standard Deviation 0.03 |
| Semaglutide 0.05 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Eosinophils | 0.02 10^9 cells/litre (L) | Standard Deviation 0.11 |
| Semaglutide 0.1 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Eosinophils | 0.02 10^9 cells/litre (L) | Standard Deviation 0.16 |
| Semaglutide 0.1 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Neutrophils | -0.07 10^9 cells/litre (L) | Standard Deviation 1.22 |
| Semaglutide 0.1 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Lymphocytes | -0.16 10^9 cells/litre (L) | Standard Deviation 0.46 |
| Semaglutide 0.1 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Monocytes | -0.04 10^9 cells/litre (L) | Standard Deviation 0.12 |
| Semaglutide 0.1 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Leucocytes | -0.24 10^9 cells/litre (L) | Standard Deviation 1.44 |
| Semaglutide 0.1 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Thrombocytes | 2.95 10^9 cells/litre (L) | Standard Deviation 43.02 |
| Semaglutide 0.1 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Basophils | -0.00 10^9 cells/litre (L) | Standard Deviation 0.04 |
| Semaglutide 0.2 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Monocytes | 0.01 10^9 cells/litre (L) | Standard Deviation 0.12 |
| Semaglutide 0.2 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Basophils | -0.00 10^9 cells/litre (L) | Standard Deviation 0.03 |
| Semaglutide 0.2 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Eosinophils | -0.01 10^9 cells/litre (L) | Standard Deviation 0.09 |
| Semaglutide 0.2 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Lymphocytes | -0.17 10^9 cells/litre (L) | Standard Deviation 0.38 |
| Semaglutide 0.2 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Neutrophils | -0.05 10^9 cells/litre (L) | Standard Deviation 1.62 |
| Semaglutide 0.2 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Leucocytes | -0.23 10^9 cells/litre (L) | Standard Deviation 1.81 |
| Semaglutide 0.2 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Thrombocytes | -8.17 10^9 cells/litre (L) | Standard Deviation 42.59 |
| Semaglutide 0.3 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Neutrophils | -0.22 10^9 cells/litre (L) | Standard Deviation 1.24 |
| Semaglutide 0.3 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Thrombocytes | 2.79 10^9 cells/litre (L) | Standard Deviation 41.28 |
| Semaglutide 0.3 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Leucocytes | -0.50 10^9 cells/litre (L) | Standard Deviation 1.42 |
| Semaglutide 0.3 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Eosinophils | -0.02 10^9 cells/litre (L) | Standard Deviation 0.13 |
| Semaglutide 0.3 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Basophils | -0.01 10^9 cells/litre (L) | Standard Deviation 0.03 |
| Semaglutide 0.3 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Monocytes | -0.02 10^9 cells/litre (L) | Standard Deviation 0.1 |
| Semaglutide 0.3 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Lymphocytes | -0.24 10^9 cells/litre (L) | Standard Deviation 0.5 |
| Semaglutide 0.4 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Basophils | -0.00 10^9 cells/litre (L) | Standard Deviation 0.03 |
| Semaglutide 0.4 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Eosinophils | 0.00 10^9 cells/litre (L) | Standard Deviation 0.08 |
| Semaglutide 0.4 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Monocytes | -0.02 10^9 cells/litre (L) | Standard Deviation 0.12 |
| Semaglutide 0.4 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Lymphocytes | -0.15 10^9 cells/litre (L) | Standard Deviation 0.36 |
| Semaglutide 0.4 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Leucocytes | -0.68 10^9 cells/litre (L) | Standard Deviation 1.41 |
| Semaglutide 0.4 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Neutrophils | -0.51 10^9 cells/litre (L) | Standard Deviation 1.27 |
| Semaglutide 0.4 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Thrombocytes | -0.52 10^9 cells/litre (L) | Standard Deviation 39.59 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Thrombocytes | -5.76 10^9 cells/litre (L) | Standard Deviation 53.41 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Eosinophils | 0.01 10^9 cells/litre (L) | Standard Deviation 0.09 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Leucocytes | -0.66 10^9 cells/litre (L) | Standard Deviation 1.9 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Lymphocytes | -0.08 10^9 cells/litre (L) | Standard Deviation 0.41 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Basophils | -0.01 10^9 cells/litre (L) | Standard Deviation 0.04 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Neutrophils | -0.57 10^9 cells/litre (L) | Standard Deviation 1.76 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Monocytes | -0.01 10^9 cells/litre (L) | Standard Deviation 0.13 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Lymphocytes | -0.14 10^9 cells/litre (L) | Standard Deviation 0.37 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Eosinophils | -0.01 10^9 cells/litre (L) | Standard Deviation 0.08 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Neutrophils | -0.23 10^9 cells/litre (L) | Standard Deviation 1.19 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Leucocytes | -0.40 10^9 cells/litre (L) | Standard Deviation 1.43 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Thrombocytes | -3.32 10^9 cells/litre (L) | Standard Deviation 45.02 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Monocytes | -0.03 10^9 cells/litre (L) | Standard Deviation 0.11 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Basophils | 0.00 10^9 cells/litre (L) | Standard Deviation 0.04 |
| Liraglutide 3.0 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Neutrophils | -0.12 10^9 cells/litre (L) | Standard Deviation 1.11 |
| Liraglutide 3.0 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Basophils | -0.00 10^9 cells/litre (L) | Standard Deviation 0.04 |
| Liraglutide 3.0 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Eosinophils | 0.01 10^9 cells/litre (L) | Standard Deviation 0.1 |
| Liraglutide 3.0 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Thrombocytes | 4.83 10^9 cells/litre (L) | Standard Deviation 37.7 |
| Liraglutide 3.0 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Lymphocytes | -0.06 10^9 cells/litre (L) | Standard Deviation 0.42 |
| Liraglutide 3.0 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Leucocytes | -0.17 10^9 cells/litre (L) | Standard Deviation 1.41 |
| Liraglutide 3.0 mg | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Monocytes | -0.01 10^9 cells/litre (L) | Standard Deviation 0.14 |
| Placebo Pool | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Eosinophils | 0.00 10^9 cells/litre (L) | Standard Deviation 0.08 |
| Placebo Pool | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Leucocytes | -0.44 10^9 cells/litre (L) | Standard Deviation 1.62 |
| Placebo Pool | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Lymphocytes | -0.09 10^9 cells/litre (L) | Standard Deviation 0.66 |
| Placebo Pool | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Neutrophils | -0.33 10^9 cells/litre (L) | Standard Deviation 1.28 |
| Placebo Pool | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Basophils | 0.00 10^9 cells/litre (L) | Standard Deviation 0.04 |
| Placebo Pool | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Thrombocytes | -6.11 10^9 cells/litre (L) | Standard Deviation 39.11 |
| Placebo Pool | Change in Haematology: Thrombocytes, Leucocytes and Differential Count | Monocytes | -0.02 10^9 cells/litre (L) | Standard Deviation 0.11 |
Secondary
Change in HbA1c
Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline HbA1c as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in HbA1c | -0.13 Percentage of HbA1c | Standard Error 0.03 |
| Semaglutide 0.1 mg | Change in HbA1c | -0.21 Percentage of HbA1c | Standard Error 0.03 |
| Semaglutide 0.2 mg | Change in HbA1c | -0.28 Percentage of HbA1c | Standard Error 0.03 |
| Semaglutide 0.3 mg | Change in HbA1c | -0.23 Percentage of HbA1c | Standard Error 0.03 |
| Semaglutide 0.4 mg | Change in HbA1c | -0.29 Percentage of HbA1c | Standard Error 0.03 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in HbA1c | -0.25 Percentage of HbA1c | Standard Error 0.03 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in HbA1c | -0.34 Percentage of HbA1c | Standard Error 0.03 |
| Liraglutide 3.0 mg | Change in HbA1c | -0.21 Percentage of HbA1c | Standard Error 0.03 |
| Placebo Pool | Change in HbA1c | -0.01 Percentage of HbA1c | Standard Error 0.03 |
Secondary
Change in hsCRP
Change from baseline (week 0) in high-sensitivity C-reactive protein (hsCRP) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline hsCRP as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in hsCRP | 0.71 Milligrams per decilitre (mg/dL) | Standard Error 0.07 |
| Semaglutide 0.1 mg | Change in hsCRP | 0.65 Milligrams per decilitre (mg/dL) | Standard Error 0.06 |
| Semaglutide 0.2 mg | Change in hsCRP | 0.57 Milligrams per decilitre (mg/dL) | Standard Error 0.05 |
| Semaglutide 0.3 mg | Change in hsCRP | 0.66 Milligrams per decilitre (mg/dL) | Standard Error 0.06 |
| Semaglutide 0.4 mg | Change in hsCRP | 0.54 Milligrams per decilitre (mg/dL) | Standard Error 0.05 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in hsCRP | 0.58 Milligrams per decilitre (mg/dL) | Standard Error 0.05 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in hsCRP | 0.44 Milligrams per decilitre (mg/dL) | Standard Error 0.04 |
| Liraglutide 3.0 mg | Change in hsCRP | 0.72 Milligrams per decilitre (mg/dL) | Standard Error 0.06 |
| Placebo Pool | Change in hsCRP | 0.82 Milligrams per decilitre (mg/dL) | Standard Error 0.07 |
Secondary
Change in IWQoL Lite
The planned analyses of the Impact of Weight on Quality of Life Lite (IWQoL-Lite) for Clinical Trials scores were not performed. The measure was still under development, and Novo Nordisk had not obtained a validated scoring of the instrument by the time of analysis of the trial results. Therefore, the total and subdomain scores on the IWQoL-Lite could not be provided.
Time frame: Week 0, Week 52
Population: This outcome measure was not analysed.
Secondary
Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA)
Change from baseline (week 0) in lipids (total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, very low density lipoprotein (VLDL) cholesterol and triglycerides) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and respective baseline lipid value as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site. Free fatty acid (FFA) results are not presented as the values were considered invalid. The shipment of the samples to be tested for FFA was not as per the requirement.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = FAS which included all randomised participants. Number Analyzed = number of participants in the FAS who contributed to the analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 0.05 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Total cholesterol | 0.96 Millimoles per litre (mmol/L) | Standard Error 0.02 |
| Semaglutide 0.05 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Triglycerides | 0.89 Millimoles per litre (mmol/L) | Standard Error 0.04 |
| Semaglutide 0.05 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | HDL cholesterol | 0.99 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Semaglutide 0.05 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | LDL cholesterol | 0.97 Millimoles per litre (mmol/L) | Standard Error 0.02 |
| Semaglutide 0.05 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | VLDL cholesterol | 0.90 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Semaglutide 0.1 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Triglycerides | 0.88 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Semaglutide 0.1 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | HDL cholesterol | 1.02 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Semaglutide 0.1 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Total cholesterol | 0.95 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Semaglutide 0.1 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | LDL cholesterol | 0.93 Millimoles per litre (mmol/L) | Standard Error 0.02 |
| Semaglutide 0.1 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | VLDL cholesterol | 0.89 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Semaglutide 0.2 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | LDL cholesterol | 0.93 Millimoles per litre (mmol/L) | Standard Error 0.02 |
| Semaglutide 0.2 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Total cholesterol | 0.93 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Semaglutide 0.2 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | VLDL cholesterol | 0.81 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Semaglutide 0.2 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | HDL cholesterol | 1.02 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Semaglutide 0.2 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Triglycerides | 0.81 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Semaglutide 0.3 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | LDL cholesterol | 0.92 Millimoles per litre (mmol/L) | Standard Error 0.02 |
| Semaglutide 0.3 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Total cholesterol | 0.93 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Semaglutide 0.3 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | HDL cholesterol | 1.02 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Semaglutide 0.3 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | VLDL cholesterol | 0.85 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Semaglutide 0.3 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Triglycerides | 0.85 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Semaglutide 0.4 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Total cholesterol | 0.93 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Semaglutide 0.4 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | VLDL cholesterol | 0.81 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Semaglutide 0.4 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | HDL cholesterol | 1.00 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Semaglutide 0.4 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | LDL cholesterol | 0.93 Millimoles per litre (mmol/L) | Standard Error 0.02 |
| Semaglutide 0.4 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Triglycerides | 0.80 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Total cholesterol | 0.93 Millimoles per litre (mmol/L) | Standard Error 0.02 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Triglycerides | 0.87 Millimoles per litre (mmol/L) | Standard Error 0.04 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | LDL cholesterol | 0.92 Millimoles per litre (mmol/L) | Standard Error 0.02 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | VLDL cholesterol | 0.87 Millimoles per litre (mmol/L) | Standard Error 0.04 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | HDL cholesterol | 1.00 Millimoles per litre (mmol/L) | Standard Error 0.02 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | LDL cholesterol | 0.91 Millimoles per litre (mmol/L) | Standard Error 0.02 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | VLDL cholesterol | 0.81 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Triglycerides | 0.80 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Total cholesterol | 0.92 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | HDL cholesterol | 1.01 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Liraglutide 3.0 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | HDL cholesterol | 1.00 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Liraglutide 3.0 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | LDL cholesterol | 0.95 Millimoles per litre (mmol/L) | Standard Error 0.02 |
| Liraglutide 3.0 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | VLDL cholesterol | 0.91 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Liraglutide 3.0 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Triglycerides | 0.90 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Liraglutide 3.0 mg | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Total cholesterol | 0.96 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Placebo Pool | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Triglycerides | 0.95 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Placebo Pool | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | Total cholesterol | 0.97 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Placebo Pool | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | VLDL cholesterol | 0.95 Millimoles per litre (mmol/L) | Standard Error 0.03 |
| Placebo Pool | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | HDL cholesterol | 1.00 Millimoles per litre (mmol/L) | Standard Error 0.01 |
| Placebo Pool | Change in Lipids (Total Cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL Cholesterol, Triglycerides and FFA) | LDL cholesterol | 0.97 Millimoles per litre (mmol/L) | Standard Error 0.02 |
Secondary
Change in Mental Health Assessed by C-SSRS
Presented results are the number of participants with Columbia Suicidality Severity Rating Scale (C-SSRS) results recorded during baseline (week 0) and post baseline (week 4-52) visits. For classification of the events reported on the C-SSRS, the following categories were used: 1) Suicidal ideation, 2) Suicidal behaviour and 3) Non-suicidal self-injurious behaviour. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0 and Week 4-59
Population: Overall number of participants analyzed = SAS which included all participants receiving at least one dose of the randomised treatment. Number Analyzed = number of participants in the SAS with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal behaviour | 0 Participants |
| Semaglutide 0.05 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal ideation | 1 Participants |
| Semaglutide 0.05 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.05 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal ideation | 0 Participants |
| Semaglutide 0.05 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.05 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal behaviour | 0 Participants |
| Semaglutide 0.1 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.1 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.1 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal ideation | 0 Participants |
| Semaglutide 0.1 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal behaviour | 0 Participants |
| Semaglutide 0.1 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal behaviour | 0 Participants |
| Semaglutide 0.1 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal ideation | 0 Participants |
| Semaglutide 0.2 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal ideation | 1 Participants |
| Semaglutide 0.2 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.2 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.2 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal behaviour | 0 Participants |
| Semaglutide 0.2 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal behaviour | 0 Participants |
| Semaglutide 0.2 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal ideation | 1 Participants |
| Semaglutide 0.3 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal ideation | 2 Participants |
| Semaglutide 0.3 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.3 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.3 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal behaviour | 0 Participants |
| Semaglutide 0.3 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal behaviour | 1 Participants |
| Semaglutide 0.3 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal ideation | 2 Participants |
| Semaglutide 0.4 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal behaviour | 0 Participants |
| Semaglutide 0.4 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal ideation | 0 Participants |
| Semaglutide 0.4 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal ideation | 1 Participants |
| Semaglutide 0.4 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal behaviour | 0 Participants |
| Semaglutide 0.4 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.4 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal behaviour | 0 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 0: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal behaviour | 0 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal ideation | 0 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal ideation | 0 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal ideation | 0 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal behaviour | 0 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal behaviour | 0 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal ideation | 0 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Non-suicidal self-injurious behaviour | 0 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Mental Health Assessed by C-SSRS | Wk 0: Non-suicidal self-injurious behaviour | 0 Participants |
| Liraglutide 3.0 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal behaviour | 0 Participants |
| Liraglutide 3.0 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Non-suicidal self-injurious behaviour | 0 Participants |
| Liraglutide 3.0 mg | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal ideation | 0 Participants |
| Liraglutide 3.0 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal behaviour | 0 Participants |
| Liraglutide 3.0 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal ideation | 2 Participants |
| Liraglutide 3.0 mg | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Non-suicidal self-injurious behaviour | 0 Participants |
| Placebo Pool | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal ideation | 0 Participants |
| Placebo Pool | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Non-suicidal self-injurious behaviour | 0 Participants |
| Placebo Pool | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal ideation | 1 Participants |
| Placebo Pool | Change in Mental Health Assessed by C-SSRS | Wk 0: Non-suicidal self-injurious behaviour | 0 Participants |
| Placebo Pool | Change in Mental Health Assessed by C-SSRS | Wk 0: Suicidal behaviour | 0 Participants |
| Placebo Pool | Change in Mental Health Assessed by C-SSRS | Wk 4-59: Suicidal behaviour | 0 Participants |
Secondary
Change in Mental Health Assessed by PHQ-9
Patient health questionnaire-9 (PHQ-9) was recorded at baseline (week 0) and week 52. The PHQ-9 questionnaire is a 9-item depression module included in the patient health questionnaire, a self-administered diagnostic tool used for assessment of mental disorders. On the PHQ-9, the participant rates the frequency of 9 items on a scale from 0 (not at all) to 3 (nearly every day). The PHQ-9 total score ranges from 0-27; total scores of 1-4 represent no depression, total scores of 5-9 represent mild depression, total scores of 10-14 represent moderate depression, total scores of 15-19 represent moderately severe depression and total scores of 20-27 represent severe depression. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = SAS which included all participants receiving at least one dose of the randomised treatment. Number Analyzed = number of participants in the SAS with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 0.05 mg | Change in Mental Health Assessed by PHQ-9 | Week 52 | 1.5 Score on a scale | Standard Deviation 2.2 |
| Semaglutide 0.05 mg | Change in Mental Health Assessed by PHQ-9 | Week 0 | 2.5 Score on a scale | Standard Deviation 3.4 |
| Semaglutide 0.1 mg | Change in Mental Health Assessed by PHQ-9 | Week 52 | 1.1 Score on a scale | Standard Deviation 1.8 |
| Semaglutide 0.1 mg | Change in Mental Health Assessed by PHQ-9 | Week 0 | 1.7 Score on a scale | Standard Deviation 2.1 |
| Semaglutide 0.2 mg | Change in Mental Health Assessed by PHQ-9 | Week 52 | 1.3 Score on a scale | Standard Deviation 2 |
| Semaglutide 0.2 mg | Change in Mental Health Assessed by PHQ-9 | Week 0 | 2.1 Score on a scale | Standard Deviation 2.6 |
| Semaglutide 0.3 mg | Change in Mental Health Assessed by PHQ-9 | Week 52 | 1.1 Score on a scale | Standard Deviation 1.7 |
| Semaglutide 0.3 mg | Change in Mental Health Assessed by PHQ-9 | Week 0 | 1.5 Score on a scale | Standard Deviation 1.9 |
| Semaglutide 0.4 mg | Change in Mental Health Assessed by PHQ-9 | Week 0 | 2.5 Score on a scale | Standard Deviation 2.9 |
| Semaglutide 0.4 mg | Change in Mental Health Assessed by PHQ-9 | Week 52 | 1.0 Score on a scale | Standard Deviation 1.8 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Mental Health Assessed by PHQ-9 | Week 0 | 1.7 Score on a scale | Standard Deviation 2.6 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Mental Health Assessed by PHQ-9 | Week 52 | 1.1 Score on a scale | Standard Deviation 1.4 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Mental Health Assessed by PHQ-9 | Week 0 | 2.0 Score on a scale | Standard Deviation 2.2 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Mental Health Assessed by PHQ-9 | Week 52 | 0.9 Score on a scale | Standard Deviation 1.6 |
| Liraglutide 3.0 mg | Change in Mental Health Assessed by PHQ-9 | Week 0 | 2.0 Score on a scale | Standard Deviation 2.5 |
| Liraglutide 3.0 mg | Change in Mental Health Assessed by PHQ-9 | Week 52 | 1.3 Score on a scale | Standard Deviation 2 |
| Placebo Pool | Change in Mental Health Assessed by PHQ-9 | Week 52 | 1.7 Score on a scale | Standard Deviation 2.6 |
| Placebo Pool | Change in Mental Health Assessed by PHQ-9 | Week 0 | 2.5 Score on a scale | Standard Deviation 3.1 |
Secondary
Change in Pulse
Change from baseline (week 0) in pulse rate was evaluated at week 52. Analysis of observed data using a mixed model for repeated measurements (MMRM) with treatment, region and sex as factors and baseline pulse as covariate, all nested within visit. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, week 52
Population: Overall number of participants analyzed = number of participants in the SAS with available data. SAS included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in Pulse | -0.33 Beats per minute | Standard Error 0.88 |
| Semaglutide 0.1 mg | Change in Pulse | 3.46 Beats per minute | Standard Error 0.83 |
| Semaglutide 0.2 mg | Change in Pulse | 1.88 Beats per minute | Standard Error 0.84 |
| Semaglutide 0.3 mg | Change in Pulse | 2.38 Beats per minute | Standard Error 0.83 |
| Semaglutide 0.4 mg | Change in Pulse | 2.54 Beats per minute | Standard Error 0.85 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Pulse | 2.34 Beats per minute | Standard Error 0.89 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Pulse | 2.15 Beats per minute | Standard Error 0.82 |
| Liraglutide 3.0 mg | Change in Pulse | 2.63 Beats per minute | Standard Error 0.84 |
| Placebo Pool | Change in Pulse | -0.86 Beats per minute | Standard Error 0.76 |
Secondary
Change in SBP
Change from baseline (week 0) in systolic blood pressure (SBP) was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline SBP as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in SBP | -4.46 Millimeters of mercury (mmHg) | Standard Error 1.2 |
| Semaglutide 0.1 mg | Change in SBP | -5.76 Millimeters of mercury (mmHg) | Standard Error 1.18 |
| Semaglutide 0.2 mg | Change in SBP | -6.26 Millimeters of mercury (mmHg) | Standard Error 1.19 |
| Semaglutide 0.3 mg | Change in SBP | -6.41 Millimeters of mercury (mmHg) | Standard Error 1.19 |
| Semaglutide 0.4 mg | Change in SBP | -5.81 Millimeters of mercury (mmHg) | Standard Error 1.16 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in SBP | -6.07 Millimeters of mercury (mmHg) | Standard Error 1.19 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in SBP | -10.26 Millimeters of mercury (mmHg) | Standard Error 1.16 |
| Liraglutide 3.0 mg | Change in SBP | -5.45 Millimeters of mercury (mmHg) | Standard Error 1.18 |
| Placebo Pool | Change in SBP | -1.58 Millimeters of mercury (mmHg) | Standard Error 1.04 |
Secondary
Change in SF-36
Short Form-36 (SF-36) is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at week 52. A positive change score indicates an improvement since baseline. Results are based on the in-trial observation period.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 0.05 mg | Change in SF-36 | Role-emotional | 3.31 Score on a scale | Standard Deviation 6.35 |
| Semaglutide 0.05 mg | Change in SF-36 | Mental health | 0.42 Score on a scale | Standard Deviation 7.76 |
| Semaglutide 0.05 mg | Change in SF-36 | General health | 2.03 Score on a scale | Standard Deviation 5.98 |
| Semaglutide 0.05 mg | Change in SF-36 | Bodily pain | 1.85 Score on a scale | Standard Deviation 10.99 |
| Semaglutide 0.05 mg | Change in SF-36 | Vitality | 1.73 Score on a scale | Standard Deviation 7.61 |
| Semaglutide 0.05 mg | Change in SF-36 | Mental component summary | 0.25 Score on a scale | Standard Deviation 5.94 |
| Semaglutide 0.05 mg | Change in SF-36 | Social functioning | 0.81 Score on a scale | Standard Deviation 6.54 |
| Semaglutide 0.05 mg | Change in SF-36 | Physical component summary | 4.16 Score on a scale | Standard Deviation 7.7 |
| Semaglutide 0.05 mg | Change in SF-36 | Physical functioning | 6.00 Score on a scale | Standard Deviation 6.92 |
| Semaglutide 0.05 mg | Change in SF-36 | Role-physical | 3.45 Score on a scale | Standard Deviation 8.24 |
| Semaglutide 0.1 mg | Change in SF-36 | Vitality | 5.16 Score on a scale | Standard Deviation 11.08 |
| Semaglutide 0.1 mg | Change in SF-36 | Role-emotional | -1.69 Score on a scale | Standard Deviation 6.61 |
| Semaglutide 0.1 mg | Change in SF-36 | Bodily pain | 3.01 Score on a scale | Standard Deviation 6.41 |
| Semaglutide 0.1 mg | Change in SF-36 | Mental component summary | -1.15 Score on a scale | Standard Deviation 6.67 |
| Semaglutide 0.1 mg | Change in SF-36 | General health | 2.51 Score on a scale | Standard Deviation 7.23 |
| Semaglutide 0.1 mg | Change in SF-36 | Physical functioning | 4.67 Score on a scale | Standard Deviation 8.17 |
| Semaglutide 0.1 mg | Change in SF-36 | Mental health | 0.24 Score on a scale | Standard Deviation 6.57 |
| Semaglutide 0.1 mg | Change in SF-36 | Physical component summary | 5.51 Score on a scale | Standard Deviation 8.04 |
| Semaglutide 0.1 mg | Change in SF-36 | Social functioning | 0.71 Score on a scale | Standard Deviation 7.04 |
| Semaglutide 0.1 mg | Change in SF-36 | Role-physical | 4.37 Score on a scale | Standard Deviation 10.23 |
| Semaglutide 0.2 mg | Change in SF-36 | Bodily pain | 4.27 Score on a scale | Standard Deviation 7.14 |
| Semaglutide 0.2 mg | Change in SF-36 | Mental health | 2.82 Score on a scale | Standard Deviation 8.67 |
| Semaglutide 0.2 mg | Change in SF-36 | Physical functioning | 6.52 Score on a scale | Standard Deviation 5.91 |
| Semaglutide 0.2 mg | Change in SF-36 | Role-emotional | 1.17 Score on a scale | Standard Deviation 7.03 |
| Semaglutide 0.2 mg | Change in SF-36 | Role-physical | 7.35 Score on a scale | Standard Deviation 8.85 |
| Semaglutide 0.2 mg | Change in SF-36 | Social functioning | 1.36 Score on a scale | Standard Deviation 7.69 |
| Semaglutide 0.2 mg | Change in SF-36 | Vitality | 8.90 Score on a scale | Standard Deviation 8.61 |
| Semaglutide 0.2 mg | Change in SF-36 | Physical component summary | 7.14 Score on a scale | Standard Deviation 6.38 |
| Semaglutide 0.2 mg | Change in SF-36 | Mental component summary | 1.45 Score on a scale | Standard Deviation 8.54 |
| Semaglutide 0.2 mg | Change in SF-36 | General health | 4.17 Score on a scale | Standard Deviation 6.52 |
| Semaglutide 0.3 mg | Change in SF-36 | Mental component summary | -1.10 Score on a scale | Standard Deviation 7.79 |
| Semaglutide 0.3 mg | Change in SF-36 | Mental health | -0.55 Score on a scale | Standard Deviation 6.48 |
| Semaglutide 0.3 mg | Change in SF-36 | Social functioning | -0.88 Score on a scale | Standard Deviation 8.81 |
| Semaglutide 0.3 mg | Change in SF-36 | Role-physical | 3.40 Score on a scale | Standard Deviation 5.43 |
| Semaglutide 0.3 mg | Change in SF-36 | Physical functioning | 4.75 Score on a scale | Standard Deviation 4.07 |
| Semaglutide 0.3 mg | Change in SF-36 | Vitality | 3.22 Score on a scale | Standard Deviation 6.42 |
| Semaglutide 0.3 mg | Change in SF-36 | Physical component summary | 4.70 Score on a scale | Standard Deviation 4.67 |
| Semaglutide 0.3 mg | Change in SF-36 | Role-emotional | 1.25 Score on a scale | Standard Deviation 7.47 |
| Semaglutide 0.3 mg | Change in SF-36 | General health | 1.20 Score on a scale | Standard Deviation 5.88 |
| Semaglutide 0.3 mg | Change in SF-36 | Bodily pain | 3.82 Score on a scale | Standard Deviation 7.11 |
| Semaglutide 0.4 mg | Change in SF-36 | Mental component summary | 1.97 Score on a scale | Standard Deviation 8.26 |
| Semaglutide 0.4 mg | Change in SF-36 | General health | 5.85 Score on a scale | Standard Deviation 7.62 |
| Semaglutide 0.4 mg | Change in SF-36 | Role-physical | 4.53 Score on a scale | Standard Deviation 7.45 |
| Semaglutide 0.4 mg | Change in SF-36 | Physical component summary | 7.67 Score on a scale | Standard Deviation 6.93 |
| Semaglutide 0.4 mg | Change in SF-36 | Mental health | 2.47 Score on a scale | Standard Deviation 7.03 |
| Semaglutide 0.4 mg | Change in SF-36 | Social functioning | 2.81 Score on a scale | Standard Deviation 9.65 |
| Semaglutide 0.4 mg | Change in SF-36 | Physical functioning | 8.74 Score on a scale | Standard Deviation 7.66 |
| Semaglutide 0.4 mg | Change in SF-36 | Vitality | 9.37 Score on a scale | Standard Deviation 9.75 |
| Semaglutide 0.4 mg | Change in SF-36 | Role-emotional | 2.24 Score on a scale | Standard Deviation 8.91 |
| Semaglutide 0.4 mg | Change in SF-36 | Bodily pain | 5.16 Score on a scale | Standard Deviation 8.02 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in SF-36 | Bodily pain | 1.88 Score on a scale | Standard Deviation 9.25 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in SF-36 | Role-physical | 7.12 Score on a scale | Standard Deviation 8.21 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in SF-36 | Vitality | 5.96 Score on a scale | Standard Deviation 7.94 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in SF-36 | Physical component summary | 7.54 Score on a scale | Standard Deviation 8.29 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in SF-36 | Social functioning | 2.23 Score on a scale | Standard Deviation 7.07 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in SF-36 | Mental health | 1.02 Score on a scale | Standard Deviation 6.93 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in SF-36 | General health | 5.85 Score on a scale | Standard Deviation 7.11 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in SF-36 | Mental component summary | -0.25 Score on a scale | Standard Deviation 6.66 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in SF-36 | Physical functioning | 7.27 Score on a scale | Standard Deviation 6.32 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in SF-36 | Role-emotional | 0.18 Score on a scale | Standard Deviation 3.69 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in SF-36 | Social functioning | -0.91 Score on a scale | Standard Deviation 11.1 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in SF-36 | Role-physical | 5.51 Score on a scale | Standard Deviation 8.49 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in SF-36 | Mental health | 1.64 Score on a scale | Standard Deviation 6.84 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in SF-36 | Vitality | 7.02 Score on a scale | Standard Deviation 9.35 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in SF-36 | Physical component summary | 7.28 Score on a scale | Standard Deviation 8.54 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in SF-36 | Mental component summary | 0.20 Score on a scale | Standard Deviation 7.13 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in SF-36 | General health | 4.81 Score on a scale | Standard Deviation 10.33 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in SF-36 | Bodily pain | 5.11 Score on a scale | Standard Deviation 10.62 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in SF-36 | Physical functioning | 7.28 Score on a scale | Standard Deviation 6.27 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in SF-36 | Role-emotional | 2.11 Score on a scale | Standard Deviation 6.17 |
| Liraglutide 3.0 mg | Change in SF-36 | Mental health | 1.91 Score on a scale | Standard Deviation 6.06 |
| Liraglutide 3.0 mg | Change in SF-36 | Bodily pain | 2.48 Score on a scale | Standard Deviation 7.46 |
| Liraglutide 3.0 mg | Change in SF-36 | Physical component summary | 6.21 Score on a scale | Standard Deviation 5.68 |
| Liraglutide 3.0 mg | Change in SF-36 | Vitality | 4.83 Score on a scale | Standard Deviation 10.84 |
| Liraglutide 3.0 mg | Change in SF-36 | Physical functioning | 6.79 Score on a scale | Standard Deviation 6.4 |
| Liraglutide 3.0 mg | Change in SF-36 | General health | 3.95 Score on a scale | Standard Deviation 6.61 |
| Liraglutide 3.0 mg | Change in SF-36 | Social functioning | 0.35 Score on a scale | Standard Deviation 5.62 |
| Liraglutide 3.0 mg | Change in SF-36 | Role-emotional | 0.25 Score on a scale | Standard Deviation 5.01 |
| Liraglutide 3.0 mg | Change in SF-36 | Mental component summary | -0.26 Score on a scale | Standard Deviation 5.69 |
| Liraglutide 3.0 mg | Change in SF-36 | Role-physical | 5.37 Score on a scale | Standard Deviation 6.82 |
| Placebo Pool | Change in SF-36 | Mental component summary | -0.05 Score on a scale | Standard Deviation 6.67 |
| Placebo Pool | Change in SF-36 | Physical component summary | 2.29 Score on a scale | Standard Deviation 9.33 |
| Placebo Pool | Change in SF-36 | Role-physical | 1.52 Score on a scale | Standard Deviation 9.47 |
| Placebo Pool | Change in SF-36 | Social functioning | -0.29 Score on a scale | Standard Deviation 7.71 |
| Placebo Pool | Change in SF-36 | General health | 1.39 Score on a scale | Standard Deviation 8.98 |
| Placebo Pool | Change in SF-36 | Vitality | 3.38 Score on a scale | Standard Deviation 10.21 |
| Placebo Pool | Change in SF-36 | Mental health | -0.38 Score on a scale | Standard Deviation 8.98 |
| Placebo Pool | Change in SF-36 | Role-emotional | 0.63 Score on a scale | Standard Deviation 5.3 |
| Placebo Pool | Change in SF-36 | Bodily pain | 1.21 Score on a scale | Standard Deviation 9.39 |
| Placebo Pool | Change in SF-36 | Physical functioning | 2.28 Score on a scale | Standard Deviation 7.56 |
Secondary
Change in Waist Circumference
Change from baseline (week 0) in waist circumference was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline waist circumference as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in Waist Circumference | -6.11 Centimetre (cm) | Standard Error 0.93 |
| Semaglutide 0.1 mg | Change in Waist Circumference | -8.75 Centimetre (cm) | Standard Error 0.9 |
| Semaglutide 0.2 mg | Change in Waist Circumference | -11.02 Centimetre (cm) | Standard Error 0.89 |
| Semaglutide 0.3 mg | Change in Waist Circumference | -10.91 Centimetre (cm) | Standard Error 0.89 |
| Semaglutide 0.4 mg | Change in Waist Circumference | -12.31 Centimetre (cm) | Standard Error 0.91 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Waist Circumference | -11.06 Centimetre (cm) | Standard Error 0.95 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Waist Circumference | -14.88 Centimetre (cm) | Standard Error 0.88 |
| Liraglutide 3.0 mg | Change in Waist Circumference | -8.35 Centimetre (cm) | Standard Error 0.89 |
| Placebo Pool | Change in Waist Circumference | -3.47 Centimetre (cm) | Standard Error 0.81 |
Secondary
Change in Waist to Hip Circumference Ratio
Change from baseline (week 0) in waist to hip circumference ratio was evaluated at week 52. Analysis of in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using an analysis of covariance model with treatment, region and sex as factors and baseline waist to hip circumference ratio as covariate. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 0.05 mg | Change in Waist to Hip Circumference Ratio | -0.01 Waist to hip circumference ratio | Standard Error 0.01 |
| Semaglutide 0.1 mg | Change in Waist to Hip Circumference Ratio | -0.02 Waist to hip circumference ratio | Standard Error 0.01 |
| Semaglutide 0.2 mg | Change in Waist to Hip Circumference Ratio | -0.02 Waist to hip circumference ratio | Standard Error 0.01 |
| Semaglutide 0.3 mg | Change in Waist to Hip Circumference Ratio | -0.03 Waist to hip circumference ratio | Standard Error 0.01 |
| Semaglutide 0.4 mg | Change in Waist to Hip Circumference Ratio | -0.02 Waist to hip circumference ratio | Standard Error 0.01 |
| Semaglutide 0.3 mg (Fast Escalation) | Change in Waist to Hip Circumference Ratio | -0.02 Waist to hip circumference ratio | Standard Error 0.01 |
| Semaglutide 0.4 mg (Fast Escalation) | Change in Waist to Hip Circumference Ratio | -0.03 Waist to hip circumference ratio | Standard Error 0.01 |
| Liraglutide 3.0 mg | Change in Waist to Hip Circumference Ratio | -0.02 Waist to hip circumference ratio | Standard Error 0.01 |
| Placebo Pool | Change in Waist to Hip Circumference Ratio | -0.01 Waist to hip circumference ratio | Standard Error 0 |
Secondary
Compliance With Nutritional Counselling
This outcome measure presents nutritional compliance results recorded at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52. Nutritional compliance was recorded on a 0 to 10 numeric rating scale (NRS), with higher scores representing better compliance.
Time frame: Week 4-52
Population: Overall number of participants analyzed = FAS which included all randomised participants. Number Analyzed = number of participants in the FAS with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-8 | 6.53 Score on a scale | Standard Deviation 2.28 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-36 | 6.87 Score on a scale | Standard Deviation 1.94 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-48 | 6.82 Score on a scale | Standard Deviation 2.08 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-16 | 6.85 Score on a scale | Standard Deviation 2.08 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-44 | 6.83 Score on a scale | Standard Deviation 1.82 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-12 | 6.70 Score on a scale | Standard Deviation 2.13 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-28 | 6.94 Score on a scale | Standard Deviation 2.04 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-32 | 6.83 Score on a scale | Standard Deviation 2.12 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-20 | 6.92 Score on a scale | Standard Deviation 2.01 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-4 | 6.85 Score on a scale | Standard Deviation 1.99 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-40 | 6.86 Score on a scale | Standard Deviation 1.96 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-52 | 7.23 Score on a scale | Standard Deviation 1.69 |
| Semaglutide 0.05 mg | Compliance With Nutritional Counselling | Week-24 | 6.49 Score on a scale | Standard Deviation 2.25 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-40 | 6.88 Score on a scale | Standard Deviation 2.4 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-28 | 7.54 Score on a scale | Standard Deviation 1.78 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-16 | 7.22 Score on a scale | Standard Deviation 1.96 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-52 | 7.22 Score on a scale | Standard Deviation 1.98 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-12 | 7.26 Score on a scale | Standard Deviation 2.26 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-48 | 7.05 Score on a scale | Standard Deviation 1.91 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-4 | 7.30 Score on a scale | Standard Deviation 1.96 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-44 | 6.95 Score on a scale | Standard Deviation 2.1 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-36 | 7.12 Score on a scale | Standard Deviation 2.02 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-32 | 6.97 Score on a scale | Standard Deviation 2.23 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-24 | 7.14 Score on a scale | Standard Deviation 2.05 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-8 | 7.24 Score on a scale | Standard Deviation 1.91 |
| Semaglutide 0.1 mg | Compliance With Nutritional Counselling | Week-20 | 7.20 Score on a scale | Standard Deviation 1.98 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-28 | 7.10 Score on a scale | Standard Deviation 2.04 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-24 | 7.07 Score on a scale | Standard Deviation 2.16 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-32 | 7.12 Score on a scale | Standard Deviation 1.93 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-48 | 6.88 Score on a scale | Standard Deviation 2 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-52 | 7.05 Score on a scale | Standard Deviation 2.04 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-4 | 7.17 Score on a scale | Standard Deviation 1.89 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-8 | 6.82 Score on a scale | Standard Deviation 2.06 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-12 | 7.22 Score on a scale | Standard Deviation 2.05 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-44 | 6.96 Score on a scale | Standard Deviation 1.92 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-16 | 7.36 Score on a scale | Standard Deviation 1.92 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-40 | 7.07 Score on a scale | Standard Deviation 2.05 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-20 | 6.87 Score on a scale | Standard Deviation 2.1 |
| Semaglutide 0.2 mg | Compliance With Nutritional Counselling | Week-36 | 7.03 Score on a scale | Standard Deviation 2.28 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-32 | 7.07 Score on a scale | Standard Deviation 2.07 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-48 | 6.92 Score on a scale | Standard Deviation 2.16 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-36 | 6.86 Score on a scale | Standard Deviation 1.98 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-28 | 7.11 Score on a scale | Standard Deviation 1.73 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-24 | 7.17 Score on a scale | Standard Deviation 1.86 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-16 | 7.04 Score on a scale | Standard Deviation 2.05 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-40 | 7.03 Score on a scale | Standard Deviation 1.97 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-52 | 6.85 Score on a scale | Standard Deviation 2.47 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-12 | 7.04 Score on a scale | Standard Deviation 2.17 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-20 | 7.14 Score on a scale | Standard Deviation 1.88 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-4 | 7.07 Score on a scale | Standard Deviation 2.27 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-44 | 6.96 Score on a scale | Standard Deviation 2.01 |
| Semaglutide 0.3 mg | Compliance With Nutritional Counselling | Week-8 | 7.13 Score on a scale | Standard Deviation 2.03 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-44 | 7.30 Score on a scale | Standard Deviation 2.13 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-32 | 7.72 Score on a scale | Standard Deviation 1.76 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-16 | 7.61 Score on a scale | Standard Deviation 1.87 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-48 | 7.12 Score on a scale | Standard Deviation 2.31 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-4 | 7.20 Score on a scale | Standard Deviation 2.19 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-8 | 7.00 Score on a scale | Standard Deviation 2.16 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-28 | 7.46 Score on a scale | Standard Deviation 1.94 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-20 | 7.64 Score on a scale | Standard Deviation 1.68 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-40 | 7.40 Score on a scale | Standard Deviation 1.89 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-36 | 7.20 Score on a scale | Standard Deviation 2.02 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-24 | 7.63 Score on a scale | Standard Deviation 1.76 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-52 | 7.36 Score on a scale | Standard Deviation 2.22 |
| Semaglutide 0.4 mg | Compliance With Nutritional Counselling | Week-12 | 7.11 Score on a scale | Standard Deviation 2.26 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-24 | 7.05 Score on a scale | Standard Deviation 1.96 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-4 | 7.05 Score on a scale | Standard Deviation 2.02 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-8 | 7.25 Score on a scale | Standard Deviation 1.84 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-12 | 7.35 Score on a scale | Standard Deviation 1.96 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-16 | 7.27 Score on a scale | Standard Deviation 2.11 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-20 | 7.24 Score on a scale | Standard Deviation 2.16 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-28 | 7.53 Score on a scale | Standard Deviation 1.57 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-32 | 7.13 Score on a scale | Standard Deviation 2.23 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-36 | 7.33 Score on a scale | Standard Deviation 1.84 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-40 | 7.01 Score on a scale | Standard Deviation 1.81 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-44 | 6.87 Score on a scale | Standard Deviation 1.98 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-48 | 7.01 Score on a scale | Standard Deviation 2.03 |
| Semaglutide 0.3 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-52 | 7.36 Score on a scale | Standard Deviation 1.85 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-8 | 7.65 Score on a scale | Standard Deviation 1.76 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-52 | 7.31 Score on a scale | Standard Deviation 2.02 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-48 | 7.23 Score on a scale | Standard Deviation 1.78 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-16 | 7.71 Score on a scale | Standard Deviation 1.66 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-4 | 7.30 Score on a scale | Standard Deviation 1.84 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-28 | 7.47 Score on a scale | Standard Deviation 1.9 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-24 | 7.55 Score on a scale | Standard Deviation 1.86 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-32 | 7.29 Score on a scale | Standard Deviation 1.91 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-40 | 7.26 Score on a scale | Standard Deviation 1.87 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-36 | 7.34 Score on a scale | Standard Deviation 1.57 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-12 | 7.64 Score on a scale | Standard Deviation 1.71 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-44 | 7.30 Score on a scale | Standard Deviation 1.98 |
| Semaglutide 0.4 mg (Fast Escalation) | Compliance With Nutritional Counselling | Week-20 | 7.74 Score on a scale | Standard Deviation 1.47 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-28 | 6.69 Score on a scale | Standard Deviation 2.04 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-4 | 7.21 Score on a scale | Standard Deviation 2.13 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-40 | 6.52 Score on a scale | Standard Deviation 2.07 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-16 | 6.98 Score on a scale | Standard Deviation 1.87 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-48 | 6.01 Score on a scale | Standard Deviation 2.49 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-36 | 6.63 Score on a scale | Standard Deviation 2.16 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-12 | 7.01 Score on a scale | Standard Deviation 1.93 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-44 | 6.60 Score on a scale | Standard Deviation 1.85 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-20 | 6.85 Score on a scale | Standard Deviation 2.2 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-52 | 6.87 Score on a scale | Standard Deviation 2.07 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-8 | 6.92 Score on a scale | Standard Deviation 2.18 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-32 | 6.94 Score on a scale | Standard Deviation 2.01 |
| Liraglutide 3.0 mg | Compliance With Nutritional Counselling | Week-24 | 6.69 Score on a scale | Standard Deviation 2.12 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-32 | 5.86 Score on a scale | Standard Deviation 2.13 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-20 | 6.24 Score on a scale | Standard Deviation 2.27 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-52 | 6.09 Score on a scale | Standard Deviation 2.39 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-36 | 6.10 Score on a scale | Standard Deviation 2.2 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-16 | 6.31 Score on a scale | Standard Deviation 2.33 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-28 | 6.34 Score on a scale | Standard Deviation 2.27 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-40 | 5.90 Score on a scale | Standard Deviation 2.1 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-12 | 6.14 Score on a scale | Standard Deviation 2.44 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-8 | 5.85 Score on a scale | Standard Deviation 2.44 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-44 | 5.99 Score on a scale | Standard Deviation 2.08 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-4 | 6.08 Score on a scale | Standard Deviation 2.32 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-48 | 6.16 Score on a scale | Standard Deviation 2.23 |
| Placebo Pool | Compliance With Nutritional Counselling | Week-24 | 6.06 Score on a scale | Standard Deviation 2.45 |
Secondary
Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score
This outcome measure presents results recorded at week 52. If a participant experienced an event of nausea within 24 hours prior to a site visit, a nausea questionnaire had to be completed. Participants experiencing such events were to answer 5 different categories in the questionnaire ('duration of nausea', 'time from the latest injection of trial product to the onset of nausea', 'time from last food intake to the onset of nausea', 'nausea accompanied by vomiting (yes/no)' and 'severity of nausea (worst during episode)'). Severity of nausea was recorded on a 0 to 10 numeric rating scale (NRS), where 0 = 'No nausea' and 10 = 'Nausea as bad as it could be'. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 52
Population: Overall number of participants analyzed = number of participants in the SAS who experienced an event of nausea within 24 hours prior to the site visit at week 52. SAS included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Last food intake to onset time: >6 hr | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Duration of nausea:<30 min | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Nausea accompanied by vomiting (Yes) | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Latest injection to onset time: 6-12 hr | 1 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Nausea accompanied by vomiting (No) | 1 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 7 | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 0 | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Latest injection to onset time: 12-18 hr | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 1 | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Duration of nausea: 30 min-2 hr | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 2 | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Latest injection to onset time: >18 hr | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 3 | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Duration of nausea: 4-8 hr | 1 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 4 | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Last food intake to onset time: 0-1 hr | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 5 | 1 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 10 | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 6 | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Last food intake to onset time: 1-2 hr | 1 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Latest injection to onset time: 0-3 hr | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 8 | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Last food intake to onset time: 2-3 hr | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 9 | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Duration of nausea: >8 hr | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Last food intake to onset time: 3-6 hr | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Latest injection to onset time: 3-6 hr | 0 Events |
| Semaglutide 0.1 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Duration of nausea: 2-4 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 7 | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Duration of nausea: 2-4 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Duration of nausea:<30 min | 1 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Duration of nausea: >8 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Latest injection to onset time: 0-3 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Latest injection to onset time: 3-6 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Latest injection to onset time: 6-12 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Latest injection to onset time: 12-18 hr | 1 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Latest injection to onset time: >18 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Last food intake to onset time: 0-1 hr | 1 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Last food intake to onset time: 1-2 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Last food intake to onset time: 2-3 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Last food intake to onset time: 3-6 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Last food intake to onset time: >6 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Nausea accompanied by vomiting (Yes) | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Nausea accompanied by vomiting (No) | 1 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 0 | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 1 | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 2 | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 3 | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 4 | 1 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 5 | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 6 | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Duration of nausea: 4-8 hr | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 8 | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 9 | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Severity of nausea: 10 | 0 Events |
| Semaglutide 0.2 mg | Nausea: Individual Scores of Nausea Questionnaire and Severity by NRS Score | Duration of nausea: 30 min-2 hr | 0 Events |
Secondary
Number of AEs During the Trial
Adverse events (AEs) were recorded from week 0 to week 59. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0-59
Population: Overall number of participants analyzed = SAS which included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 0.05 mg | Number of AEs During the Trial | 547 Events |
| Semaglutide 0.1 mg | Number of AEs During the Trial | 730 Events |
| Semaglutide 0.2 mg | Number of AEs During the Trial | 738 Events |
| Semaglutide 0.3 mg | Number of AEs During the Trial | 587 Events |
| Semaglutide 0.4 mg | Number of AEs During the Trial | 775 Events |
| Semaglutide 0.3 mg (Fast Escalation) | Number of AEs During the Trial | 737 Events |
| Semaglutide 0.4 mg (Fast Escalation) | Number of AEs During the Trial | 681 Events |
| Liraglutide 3.0 mg | Number of AEs During the Trial | 612 Events |
| Placebo Pool | Number of AEs During the Trial | 650 Events |
Secondary
Number of Hypoglycaemic Episodes During the Trial
Hypoglycaemic episodes were identified by either: 1) Subject reporting of symptoms of hypoglycaemia (low blood sugar) or 2) fasting plasma glucose (FPG) values ≤3.9 mmol/L (70 mg/dL) from blood sampling at site visits. Hypoglycaemic episodes were recorded from week 0 to week 59. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0-59
Population: Overall number of participants analyzed = SAS which included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 0.05 mg | Number of Hypoglycaemic Episodes During the Trial | 1 Episodes |
| Semaglutide 0.1 mg | Number of Hypoglycaemic Episodes During the Trial | 6 Episodes |
| Semaglutide 0.2 mg | Number of Hypoglycaemic Episodes During the Trial | 4 Episodes |
| Semaglutide 0.3 mg | Number of Hypoglycaemic Episodes During the Trial | 8 Episodes |
| Semaglutide 0.4 mg | Number of Hypoglycaemic Episodes During the Trial | 10 Episodes |
| Semaglutide 0.3 mg (Fast Escalation) | Number of Hypoglycaemic Episodes During the Trial | 20 Episodes |
| Semaglutide 0.4 mg (Fast Escalation) | Number of Hypoglycaemic Episodes During the Trial | 16 Episodes |
| Liraglutide 3.0 mg | Number of Hypoglycaemic Episodes During the Trial | 4 Episodes |
| Placebo Pool | Number of Hypoglycaemic Episodes During the Trial | 18 Episodes |
Secondary
Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week
Presented results are the number of nausea, vomiting, diarrhoea, and constipation events recorded from week 0 to week 59. Results are based on the in-trial observation period which was defined as the period from randomisation to last contact with trial site.
Time frame: Week 0-59
Population: Overall number of participants analyzed = SAS which included all participants receiving at least one dose of the randomised treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Semaglutide 0.05 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Diarrhoea | 29 Events |
| Semaglutide 0.05 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Nausea | 41 Events |
| Semaglutide 0.05 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Vomiting | 10 Events |
| Semaglutide 0.05 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Constipation | 15 Events |
| Semaglutide 0.1 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Nausea | 80 Events |
| Semaglutide 0.1 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Vomiting | 29 Events |
| Semaglutide 0.1 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Constipation | 27 Events |
| Semaglutide 0.1 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Diarrhoea | 37 Events |
| Semaglutide 0.2 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Constipation | 33 Events |
| Semaglutide 0.2 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Diarrhoea | 61 Events |
| Semaglutide 0.2 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Vomiting | 41 Events |
| Semaglutide 0.2 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Nausea | 74 Events |
| Semaglutide 0.3 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Vomiting | 18 Events |
| Semaglutide 0.3 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Diarrhoea | 54 Events |
| Semaglutide 0.3 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Nausea | 69 Events |
| Semaglutide 0.3 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Constipation | 25 Events |
| Semaglutide 0.4 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Diarrhoea | 63 Events |
| Semaglutide 0.4 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Constipation | 35 Events |
| Semaglutide 0.4 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Vomiting | 35 Events |
| Semaglutide 0.4 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Nausea | 94 Events |
| Semaglutide 0.3 mg (Fast Escalation) | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Vomiting | 32 Events |
| Semaglutide 0.3 mg (Fast Escalation) | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Nausea | 106 Events |
| Semaglutide 0.3 mg (Fast Escalation) | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Constipation | 23 Events |
| Semaglutide 0.3 mg (Fast Escalation) | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Diarrhoea | 54 Events |
| Semaglutide 0.4 mg (Fast Escalation) | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Vomiting | 47 Events |
| Semaglutide 0.4 mg (Fast Escalation) | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Nausea | 97 Events |
| Semaglutide 0.4 mg (Fast Escalation) | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Diarrhoea | 49 Events |
| Semaglutide 0.4 mg (Fast Escalation) | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Constipation | 34 Events |
| Liraglutide 3.0 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Diarrhoea | 46 Events |
| Liraglutide 3.0 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Vomiting | 17 Events |
| Liraglutide 3.0 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Nausea | 89 Events |
| Liraglutide 3.0 mg | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Constipation | 30 Events |
| Placebo Pool | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Diarrhoea | 23 Events |
| Placebo Pool | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Vomiting | 6 Events |
| Placebo Pool | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Constipation | 7 Events |
| Placebo Pool | Number of New and Ongoing Nausea, Vomiting, Diarrhoea, and Constipation Events by Week | Nausea | 30 Events |
Secondary
Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications)
Participants' status on receiving concomitant medication (antihypertensive and lipid-lowering medications) at week 0 (yes/no) and week 52 (decreased, no change, increased or missing) are presented. Results are based on the on-treatment observation period which was defined as the period from first trial product administration to last trial product administration.
Time frame: Week 0, Week 52
Population: Overall number of participants analyzed = FAS which included all randomised participants. Number Analyzed = number of participants in the FAS with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (No change) | 68 Participants |
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Missing) | 2 Participants |
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (No change) | 73 Participants |
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (No) | 83 Participants |
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (Yes) | 20 Participants |
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (Yes) | 37 Participants |
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Missing) | 2 Participants |
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Increased) | 2 Participants |
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Decreased) | 0 Participants |
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Increased) | 4 Participants |
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Decreased) | 3 Participants |
| Semaglutide 0.05 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (No) | 66 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (No change) | 83 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Decreased) | 1 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Increased) | 2 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Decreased) | 3 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (No change) | 74 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (Yes) | 17 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (Yes) | 31 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (No) | 85 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Missing) | 2 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (No) | 71 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Increased) | 9 Participants |
| Semaglutide 0.1 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Missing) | 2 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (No) | 90 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Decreased) | 8 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (No change) | 76 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Increased) | 2 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (No change) | 81 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Decreased) | 3 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Increased) | 2 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Missing) | 1 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Missing) | 1 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (No) | 75 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (Yes) | 28 Participants |
| Semaglutide 0.2 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (Yes) | 13 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Increased) | 2 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (Yes) | 15 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (Yes) | 31 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Missing) | 1 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (No) | 72 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Decreased) | 6 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (No change) | 84 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (No change) | 75 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Missing) | 1 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Increased) | 6 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Decreased) | 1 Participants |
| Semaglutide 0.3 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (No) | 88 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (No change) | 79 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Increased) | 2 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Decreased) | 10 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (Yes) | 22 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Increased) | 2 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (Yes) | 36 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Missing) | 0 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (No) | 80 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (No change) | 70 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Decreased) | 1 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Missing) | 0 Participants |
| Semaglutide 0.4 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (No) | 66 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Missing) | 0 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (Yes) | 20 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (Yes) | 32 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (No) | 70 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Decreased) | 6 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (No change) | 64 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Increased) | 5 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (No change) | 71 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Increased) | 1 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Missing) | 0 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (No) | 82 Participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Decreased) | 3 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Decreased) | 3 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Decreased) | 7 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Increased) | 4 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (Yes) | 29 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (No change) | 80 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Missing) | 0 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (No) | 90 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (Yes) | 13 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (No) | 74 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (No change) | 87 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Missing) | 0 Participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Increased) | 1 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Decreased) | 1 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Increased) | 1 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Increased) | 8 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (No change) | 74 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Decreased) | 3 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Missing) | 1 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (Yes) | 36 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Missing) | 1 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (Yes) | 25 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (No) | 78 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (No) | 67 Participants |
| Liraglutide 3.0 mg | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (No change) | 83 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Missing) | 2 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (Yes) | 50 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Decreased) | 6 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Missing) | 2 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (No change) | 89 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Antihypertensive medication (Increased) | 6 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Antihypertensive medication (No) | 86 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Decreased) | 2 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (Increased) | 5 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (Yes) | 28 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 0: Lipid-lowering medication (No) | 108 Participants |
| Placebo Pool | Participants With Change in Concomitant Medications (Antihypertensive and Lipid-lowering Medications) | Week 52: Lipid-lowering medication (No change) | 94 Participants |
Secondary
Participants With Weight Loss of ≥10% of Baseline Body Weight
Presented results are percentage of participants who lost more than or equal to 10% of their baseline (week 0) body weight at week 52. Analysis of observed in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using a binary logistic regression model with treatment, region and sex as factors and baseline body weight as covariate. In-trial observation period was defined as the period from randomisation to last contact with trial site.
Time frame: Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 0.05 mg | Participants With Weight Loss of ≥10% of Baseline Body Weight | 18.94 Percentage (%) of participants |
| Semaglutide 0.1 mg | Participants With Weight Loss of ≥10% of Baseline Body Weight | 36.57 Percentage (%) of participants |
| Semaglutide 0.2 mg | Participants With Weight Loss of ≥10% of Baseline Body Weight | 55.95 Percentage (%) of participants |
| Semaglutide 0.3 mg | Participants With Weight Loss of ≥10% of Baseline Body Weight | 57.76 Percentage (%) of participants |
| Semaglutide 0.4 mg | Participants With Weight Loss of ≥10% of Baseline Body Weight | 64.61 Percentage (%) of participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Weight Loss of ≥10% of Baseline Body Weight | 58.45 Percentage (%) of participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Weight Loss of ≥10% of Baseline Body Weight | 71.91 Percentage (%) of participants |
| Liraglutide 3.0 mg | Participants With Weight Loss of ≥10% of Baseline Body Weight | 33.98 Percentage (%) of participants |
| Placebo Pool | Participants With Weight Loss of ≥10% of Baseline Body Weight | 10.08 Percentage (%) of participants |
Secondary
Participants With Weight Loss of ≥5% of Baseline Body Weight
Presented results are percentage of participants who lost more than or equal to 5% of their baseline (week 0) body weight at week 52. Analysis of observed in-trial data with missing observations imputed from the pooled placebo arms based on a jump to reference multiple (x1000) imputation (J2R-MI) approach. Week 52 responses were analysed using a binary logistic regression model with treatment, region and sex as factors and baseline body weight as covariate. In-trial observation period was defined as the period from randomisation to last contact with trial site.
Time frame: Week 52
Population: Overall number of participants analyzed = number of participants in the FAS who contributed to the analysis. FAS included all randomised participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 0.05 mg | Participants With Weight Loss of ≥5% of Baseline Body Weight | 53.50 Percentage (%) of participants |
| Semaglutide 0.1 mg | Participants With Weight Loss of ≥5% of Baseline Body Weight | 67.49 Percentage (%) of participants |
| Semaglutide 0.2 mg | Participants With Weight Loss of ≥5% of Baseline Body Weight | 74.91 Percentage (%) of participants |
| Semaglutide 0.3 mg | Participants With Weight Loss of ≥5% of Baseline Body Weight | 80.52 Percentage (%) of participants |
| Semaglutide 0.4 mg | Participants With Weight Loss of ≥5% of Baseline Body Weight | 82.52 Percentage (%) of participants |
| Semaglutide 0.3 mg (Fast Escalation) | Participants With Weight Loss of ≥5% of Baseline Body Weight | 72.19 Percentage (%) of participants |
| Semaglutide 0.4 mg (Fast Escalation) | Participants With Weight Loss of ≥5% of Baseline Body Weight | 89.58 Percentage (%) of participants |
| Liraglutide 3.0 mg | Participants With Weight Loss of ≥5% of Baseline Body Weight | 66.12 Percentage (%) of participants |
| Placebo Pool | Participants With Weight Loss of ≥5% of Baseline Body Weight | 22.87 Percentage (%) of participants |