A Phase 2 interventional study of semaglutide and liraglutide in Metabolism and Nutrition Disorder and Obesity, sponsored by Novo Nordisk A/S. Completed at 74 sites in 8 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-04-17.
Sponsored by Novo Nordisk A/S · Phase 2, Interventional, and Treatment
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.
10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.
This study's enrollment of 957 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.
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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)
Dose 0.05 mg
Drug: semaglutide
Dose 0.05 or 0.1 mg with dose escalation every fourth week
Drug: semaglutide
Dose 0.05, 0.1 or 0.2 mg with dose escalation every fourth week
Drug: semaglutide
Dose 0.05, 0.1, 0.2 or 0.3 mg with dose escalation every fourth week
Drug: semaglutide
Dose 0.05, 0.1, 0.2, 0.3, or 0.4 mg with dose escalation every fourth week
Drug: semaglutide
Dose 0.05, 0.1, 0.2 or 0.3 mg with dose escalation every second week
Drug: semaglutide
Dose 0.05, 0.1, 0.2, 0.3, or 0.4 mg with dose escalation every second week
Drug: semaglutide
Dose 0.6, 1.2, 1.8, 2.4, 3.0 mg with dose escalation every week
Drug: liraglutide
Placebo arm matching active arm Sema 0.05 mg
Drug: placebo
Placebo arm matching active arm Sema 0.1 mg
Drug: placebo
Placebo arm matching active arm Sema 0.2 mg
Drug: placebo
Placebo arm matching active arm Sema 0.3 mg
Drug: placebo
Placebo arm matching active arm Sema 0.4 mg
Drug: placebo
Placebo arm matching active arm Sema 0.3 mg (fast dose escalation)
Drug: placebo
Placebo arm matching active arm Sema 0.4 mg (fast dose escalation)
Drug: placebo
Placebo arm matching active arm Lira 3.0 mg
Drug: placebo
Once-daily subcutaneous (s.c., under the skin) administration with dose escalation.
Once-daily subcutaneous (s.c., under the skin) administration with dose escalation.
Once-daily subcutaneous (s.c., under the skin) administration.
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
| Milestone | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Started | 103 | 102 | 103 | 103 | 102 | 102 | 103 | 103 | 136 |
| Full analysis set | 103 | 102 | 103 | 103 | 102 | 102 | 103 | 103 | 136 |
| Safety analysis set | 103 | 102 | 103 | 103 | 102 | 102 | 103 | 103 | 136 |
| Completed | 92 | 95 | 94 | 96 | 100 | 96 | 100 | 96 | 123 |
| Not completed | 11 | 7 | 9 | 7 | 2 | 6 | 3 | 7 | 13 |
| Withdrew: Withdrawal by subject | 5 | 4 | 6 | 4 | 1 | 1 | 0 | 1 | 7 |
| Withdrew: Lost to follow-up | 5 | 3 | 2 | 3 | 1 | 5 | 2 | 6 | 6 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Unclassified | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
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.
| Percentage (%) of body weight | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Relative Change in Body Weight (%) | -5.99 ± 0.85 | -8.62 ± 0.84 | -11.60 ± 0.85 | -11.17 ± 0.85 | -13.84 ± 0.83 | -11.38 ± 0.85 | -16.29 ± 0.83 | -7.76 ± 0.85 | -2.29 ± 0.74 |
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.
| Percentage (%) of participants | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Participants With Weight Loss of ≥5% of Baseline Body Weight | 53.50 | 67.49 | 74.91 | 80.52 | 82.52 | 72.19 | 89.58 | 66.12 | 22.87 |
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.
| Percentage (%) of participants | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Participants With Weight Loss of ≥10% of Baseline Body Weight | 18.94 | 36.57 | 55.95 | 57.76 | 64.61 | 58.45 | 71.91 | 33.98 | 10.08 |
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.
| Kilogram (kg) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in Body Weight (kg) | -6.66 ± 0.94 | -9.34 ± 0.93 | -12.30 ± 0.93 | -12.45 ± 0.93 | -15.15 ± 0.92 | -12.54 ± 0.93 | -17.36 ± 0.92 | -8.47 ± 0.93 | -2.48 ± 0.82 |
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.
| Centimetre (cm) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in Waist Circumference | -6.11 ± 0.93 | -8.75 ± 0.90 | -11.02 ± 0.89 | -10.91 ± 0.89 | -12.31 ± 0.91 | -11.06 ± 0.95 | -14.88 ± 0.88 | -8.35 ± 0.89 | -3.47 ± 0.81 |
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.
| Waist to hip circumference ratio | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in Waist to Hip Circumference Ratio | -0.01 ± 0.01 | -0.02 ± 0.01 | -0.02 ± 0.01 | -0.03 ± 0.01 | -0.02 ± 0.01 | -0.02 ± 0.01 | -0.03 ± 0.01 | -0.02 ± 0.01 | -0.01 ± 0.00 |
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.
| Kilogram per square meter (kg/m^2) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in BMI | -2.37 ± 0.33 | -3.36 ± 0.33 | -4.38 ± 0.33 | -4.40 ± 0.33 | -5.40 ± 0.33 | -4.48 ± 0.33 | -6.21 ± 0.33 | -3.03 ± 0.33 | -0.88 ± 0.29 |
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.
| Percentage of HbA1c | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in HbA1c | -0.13 ± 0.03 | -0.21 ± 0.03 | -0.28 ± 0.03 | -0.23 ± 0.03 | -0.29 ± 0.03 | -0.25 ± 0.03 | -0.34 ± 0.03 | -0.21 ± 0.03 | -0.01 ± 0.03 |
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.
| Millimoles per litre (mmol/L) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in FPG | -0.29 ± 0.06 | -0.35 ± 0.06 | -0.40 ± 0.06 | -0.39 ± 0.06 | -0.43 ± 0.06 | -0.38 ± 0.06 | -0.51 ± 0.06 | -0.35 ± 0.06 | 0.01 ± 0.05 |
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.
No measurements were reported for this outcome.
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.
| Millimeters of mercury (mmHg) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in SBP | -4.46 ± 1.20 | -5.76 ± 1.18 | -6.26 ± 1.19 | -6.41 ± 1.19 | -5.81 ± 1.16 | -6.07 ± 1.19 | -10.26 ± 1.16 | -5.45 ± 1.18 | -1.58 ± 1.04 |
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.
| Millimeters of mercury (mmHg) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in DBP | -2.55 ± 0.84 | -2.65 ± 0.82 | -4.09 ± 0.83 | -2.98 ± 0.83 | -3.61 ± 0.80 | -2.20 ± 0.83 | -5.52 ± 0.80 | -2.70 ± 0.82 | -1.50 ± 0.73 |
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.
| Millimoles per litre (mmol/L) | 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 cholesterol | 0.96 ± 0.02 | 0.95 ± 0.01 | 0.93 ± 0.01 | 0.93 ± 0.01 | 0.93 ± 0.01 | 0.93 ± 0.02 | 0.92 ± 0.01 | 0.96 ± 0.01 | 0.97 ± 0.01 |
| LDL cholesterol | 0.97 ± 0.02 | 0.93 ± 0.02 | 0.93 ± 0.02 | 0.92 ± 0.02 | 0.93 ± 0.02 | 0.92 ± 0.02 | 0.91 ± 0.02 | 0.95 ± 0.02 | 0.97 ± 0.02 |
| HDL cholesterol | 0.99 ± 0.01 | 1.02 ± 0.01 | 1.02 ± 0.01 | 1.02 ± 0.01 | 1.00 ± 0.01 | 1.00 ± 0.02 | 1.01 ± 0.01 | 1.00 ± 0.01 | 1.00 ± 0.01 |
| VLDL cholesterol | 0.90 ± 0.03 | 0.89 ± 0.03 | 0.81 ± 0.03 | 0.85 ± 0.03 | 0.81 ± 0.03 | 0.87 ± 0.04 | 0.81 ± 0.03 | 0.91 ± 0.03 | 0.95 ± 0.03 |
| Triglycerides | 0.89 ± 0.04 | 0.88 ± 0.03 | 0.81 ± 0.03 | 0.85 ± 0.03 | 0.80 ± 0.03 | 0.87 ± 0.04 | 0.80 ± 0.03 | 0.90 ± 0.03 | 0.95 ± 0.03 |
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.
| Milligrams per decilitre (mg/dL) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in hsCRP | 0.71 ± 0.07 | 0.65 ± 0.06 | 0.57 ± 0.05 | 0.66 ± 0.06 | 0.54 ± 0.05 | 0.58 ± 0.05 | 0.44 ± 0.04 | 0.72 ± 0.06 | 0.82 ± 0.07 |
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.
No measurements were reported for this outcome.
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.
| Score on a scale | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Bodily pain | 1.85 ± 10.99 | 3.01 ± 6.41 | 4.27 ± 7.14 | 3.82 ± 7.11 | 5.16 ± 8.02 | 1.88 ± 9.25 | 5.11 ± 10.62 | 2.48 ± 7.46 | 1.21 ± 9.39 |
| General health | 2.03 ± 5.98 | 2.51 ± 7.23 | 4.17 ± 6.52 | 1.20 ± 5.88 | 5.85 ± 7.62 | 5.85 ± 7.11 | 4.81 ± 10.33 | 3.95 ± 6.61 | 1.39 ± 8.98 |
| Mental health | 0.42 ± 7.76 | 0.24 ± 6.57 | 2.82 ± 8.67 | -0.55 ± 6.48 | 2.47 ± 7.03 | 1.02 ± 6.93 | 1.64 ± 6.84 | 1.91 ± 6.06 | -0.38 ± 8.98 |
| Physical functioning | 6.00 ± 6.92 | 4.67 ± 8.17 | 6.52 ± 5.91 | 4.75 ± 4.07 | 8.74 ± 7.66 | 7.27 ± 6.32 | 7.28 ± 6.27 | 6.79 ± 6.40 | 2.28 ± 7.56 |
| Role-emotional | 3.31 ± 6.35 | -1.69 ± 6.61 | 1.17 ± 7.03 | 1.25 ± 7.47 | 2.24 ± 8.91 | 0.18 ± 3.69 | 2.11 ± 6.17 | 0.25 ± 5.01 | 0.63 ± 5.30 |
| Role-physical | 3.45 ± 8.24 | 4.37 ± 10.23 | 7.35 ± 8.85 | 3.40 ± 5.43 | 4.53 ± 7.45 | 7.12 ± 8.21 | 5.51 ± 8.49 | 5.37 ± 6.82 | 1.52 ± 9.47 |
| Social functioning | 0.81 ± 6.54 | 0.71 ± 7.04 | 1.36 ± 7.69 | -0.88 ± 8.81 | 2.81 ± 9.65 | 2.23 ± 7.07 | -0.91 ± 11.10 | 0.35 ± 5.62 | -0.29 ± 7.71 |
| Vitality | 1.73 ± 7.61 | 5.16 ± 11.08 | 8.90 ± 8.61 | 3.22 ± 6.42 | 9.37 ± 9.75 | 5.96 ± 7.94 | 7.02 ± 9.35 | 4.83 ± 10.84 | 3.38 ± 10.21 |
| Physical component summary | 4.16 ± 7.70 | 5.51 ± 8.04 | 7.14 ± 6.38 | 4.70 ± 4.67 | 7.67 ± 6.93 | 7.54 ± 8.29 | 7.28 ± 8.54 | 6.21 ± 5.68 | 2.29 ± 9.33 |
| Mental component summary | 0.25 ± 5.94 | -1.15 ± 6.67 | 1.45 ± 8.54 | -1.10 ± 7.79 | 1.97 ± 8.26 | -0.25 ± 6.66 | 0.20 ± 7.13 | -0.26 ± 5.69 | -0.05 ± 6.67 |
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.
| Participants | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Week 0: Antihypertensive medication (Yes) | 37 | 31 | 28 | 31 | 36 | 32 | 29 | 36 | 50 |
| Week 0: Antihypertensive medication (No) | 66 | 71 | 75 | 72 | 66 | 70 | 74 | 67 | 86 |
| Week 52: Antihypertensive medication (Decreased) | 3 | 3 | 8 | 6 | 10 | 6 | 7 | 3 | 6 |
| Week 52: Antihypertensive medication (No change) | 68 | 74 | 76 | 75 | 70 | 64 | 80 | 74 | 89 |
| Week 52: Antihypertensive medication (Increased) | 4 | 9 | 2 | 6 | 2 | 5 | 4 | 8 | 6 |
| Week 52: Antihypertensive medication (Missing) | 2 | 2 | 1 | 1 | 0 | 0 | 0 | 1 | 2 |
| Week 0: Lipid-lowering medication (Yes) | 20 | 17 | 13 | 15 | 22 | 20 | 13 | 25 | 28 |
| Week 0: Lipid-lowering medication (No) | 83 | 85 | 90 | 88 | 80 | 82 | 90 | 78 | 108 |
| Week 52: Lipid-lowering medication (Decreased) | 0 | 1 | 3 | 1 | 1 | 3 | 3 | 1 | 2 |
| Week 52: Lipid-lowering medication (No change) | 73 | 83 | 81 | 84 | 79 | 71 | 87 | 83 | 94 |
| Week 52: Lipid-lowering medication (Increased) | 2 | 2 | 2 | 2 | 2 | 1 | 1 | 1 | 5 |
| Week 52: Lipid-lowering medication (Missing) | 2 | 2 | 1 | 1 | 0 | 0 | 0 | 1 | 2 |
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.
| Score on a scale | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Week-4 | 6.85 ± 1.99 | 7.30 ± 1.96 | 7.17 ± 1.89 | 7.07 ± 2.27 | 7.20 ± 2.19 | 7.05 ± 2.02 | 7.30 ± 1.84 | 7.21 ± 2.13 | 6.08 ± 2.32 |
| Week-8 | 6.53 ± 2.28 | 7.24 ± 1.91 | 6.82 ± 2.06 | 7.13 ± 2.03 | 7.00 ± 2.16 | 7.25 ± 1.84 | 7.65 ± 1.76 | 6.92 ± 2.18 | 5.85 ± 2.44 |
| Week-12 | 6.70 ± 2.13 | 7.26 ± 2.26 | 7.22 ± 2.05 | 7.04 ± 2.17 | 7.11 ± 2.26 | 7.35 ± 1.96 | 7.64 ± 1.71 | 7.01 ± 1.93 | 6.14 ± 2.44 |
| Week-16 | 6.85 ± 2.08 | 7.22 ± 1.96 | 7.36 ± 1.92 | 7.04 ± 2.05 | 7.61 ± 1.87 | 7.27 ± 2.11 | 7.71 ± 1.66 | 6.98 ± 1.87 | 6.31 ± 2.33 |
| Week-20 | 6.92 ± 2.01 | 7.20 ± 1.98 | 6.87 ± 2.10 | 7.14 ± 1.88 | 7.64 ± 1.68 | 7.24 ± 2.16 | 7.74 ± 1.47 | 6.85 ± 2.20 | 6.24 ± 2.27 |
| Week-24 | 6.49 ± 2.25 | 7.14 ± 2.05 | 7.07 ± 2.16 | 7.17 ± 1.86 | 7.63 ± 1.76 | 7.05 ± 1.96 | 7.55 ± 1.86 | 6.69 ± 2.12 | 6.06 ± 2.45 |
| Week-28 | 6.94 ± 2.04 | 7.54 ± 1.78 | 7.10 ± 2.04 | 7.11 ± 1.73 | 7.46 ± 1.94 | 7.53 ± 1.57 | 7.47 ± 1.90 | 6.69 ± 2.04 | 6.34 ± 2.27 |
| Week-32 | 6.83 ± 2.12 | 6.97 ± 2.23 | 7.12 ± 1.93 | 7.07 ± 2.07 | 7.72 ± 1.76 | 7.13 ± 2.23 | 7.29 ± 1.91 | 6.94 ± 2.01 | 5.86 ± 2.13 |
| Week-36 | 6.87 ± 1.94 | 7.12 ± 2.02 | 7.03 ± 2.28 | 6.86 ± 1.98 | 7.20 ± 2.02 | 7.33 ± 1.84 | 7.34 ± 1.57 | 6.63 ± 2.16 | 6.10 ± 2.20 |
| Week-40 | 6.86 ± 1.96 | 6.88 ± 2.40 | 7.07 ± 2.05 | 7.03 ± 1.97 | 7.40 ± 1.89 | 7.01 ± 1.81 | 7.26 ± 1.87 | 6.52 ± 2.07 | 5.90 ± 2.10 |
| Week-44 | 6.83 ± 1.82 | 6.95 ± 2.10 | 6.96 ± 1.92 | 6.96 ± 2.01 | 7.30 ± 2.13 | 6.87 ± 1.98 | 7.30 ± 1.98 | 6.60 ± 1.85 | 5.99 ± 2.08 |
| Week-48 | 6.82 ± 2.08 | 7.05 ± 1.91 | 6.88 ± 2.00 | 6.92 ± 2.16 | 7.12 ± 2.31 | 7.01 ± 2.03 | 7.23 ± 1.78 | 6.01 ± 2.49 | 6.16 ± 2.23 |
| Week-52 | 7.23 ± 1.69 | 7.22 ± 1.98 | 7.05 ± 2.04 | 6.85 ± 2.47 | 7.36 ± 2.22 | 7.36 ± 1.85 | 7.31 ± 2.02 | 6.87 ± 2.07 | 6.09 ± 2.39 |
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.
| Events | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Number of AEs During the Trial | 547 | 730 | 738 | 587 | 775 | 737 | 681 | 612 | 650 |
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.
| Episodes | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Number of Hypoglycaemic Episodes During the Trial | 1 | 6 | 4 | 8 | 10 | 20 | 16 | 4 | 18 |
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.
| Events | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Nausea | 41 | 80 | 74 | 69 | 94 | 106 | 97 | 89 | 30 |
| Vomiting | 10 | 29 | 41 | 18 | 35 | 32 | 47 | 17 | 6 |
| Diarrhoea | 29 | 37 | 61 | 54 | 63 | 54 | 49 | 46 | 23 |
| Constipation | 15 | 27 | 33 | 25 | 35 | 23 | 34 | 30 | 7 |
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.
| Events | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Duration of nausea:<30 min | — | 0 | 1 | — | — | — | — | — | — |
| Duration of nausea: 30 min-2 hr | — | 0 | 0 | — | — | — | — | — | — |
| Duration of nausea: 2-4 hr | — | 0 | 0 | — | — | — | — | — | — |
| Duration of nausea: 4-8 hr | — | 1 | 0 | — | — | — | — | — | — |
| Duration of nausea: >8 hr | — | 0 | 0 | — | — | — | — | — | — |
| Latest injection to onset time: 0-3 hr | — | 0 | 0 | — | — | — | — | — | — |
| Latest injection to onset time: 3-6 hr | — | 0 | 0 | — | — | — | — | — | — |
| Latest injection to onset time: 6-12 hr | — | 1 | 0 | — | — | — | — | — | — |
| Latest injection to onset time: 12-18 hr | — | 0 | 1 | — | — | — | — | — | — |
| Latest injection to onset time: >18 hr | — | 0 | 0 | — | — | — | — | — | — |
| Last food intake to onset time: 0-1 hr | — | 0 | 1 | — | — | — | — | — | — |
| Last food intake to onset time: 1-2 hr | — | 1 | 0 | — | — | — | — | — | — |
| Last food intake to onset time: 2-3 hr | — | 0 | 0 | — | — | — | — | — | — |
| Last food intake to onset time: 3-6 hr | — | 0 | 0 | — | — | — | — | — | — |
| Last food intake to onset time: >6 hr | — | 0 | 0 | — | — | — | — | — | — |
| Nausea accompanied by vomiting (Yes) | — | 0 | 0 | — | — | — | — | — | — |
| Nausea accompanied by vomiting (No) | — | 1 | 1 | — | — | — | — | — | — |
| Severity of nausea: 0 | — | 0 | 0 | — | — | — | — | — | — |
| Severity of nausea: 1 | — | 0 | 0 | — | — | — | — | — | — |
| Severity of nausea: 2 | — | 0 | 0 | — | — | — | — | — | — |
| Severity of nausea: 3 | — | 0 | 0 | — | — | — | — | — | — |
| Severity of nausea: 4 | — | 0 | 1 | — | — | — | — | — | — |
| Severity of nausea: 5 | — | 1 | 0 | — | — | — | — | — | — |
| Severity of nausea: 6 | — | 0 | 0 | — | — | — | — | — | — |
| Severity of nausea: 7 | — | 0 | 0 | — | — | — | — | — | — |
| Severity of nausea: 8 | — | 0 | 0 | — | — | — | — | — | — |
| Severity of nausea: 9 | — | 0 | 0 | — | — | — | — | — | — |
| Severity of nausea: 10 | — | 0 | 0 | — | — | — | — | — | — |
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.
| Participants | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Week: 0 — Normal | 70 | 69 | 74 | 62 | 62 | 70 | 74 | 68 | 85 |
| Week: 0 — Abnormal, NCS | 33 | 31 | 29 | 41 | 38 | 32 | 27 | 35 | 51 |
| Week: 0 — Abnormal, CS | 0 | 2 | 0 | 0 | 2 | 0 | 2 | 0 | 0 |
| Week: 52 — Normal | 57 | 73 | 67 | 58 | 57 | 55 | 64 | 59 | 66 |
| Week: 52 — Abnormal, NCS | 25 | 18 | 18 | 31 | 29 | 21 | 28 | 26 | 40 |
| Week: 52 — Abnormal, CS | 0 | 0 | 2 | 0 | 1 | 1 | 0 | 1 | 0 |
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.
| Beats per minute | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in Pulse | -0.33 ± 0.88 | 3.46 ± 0.83 | 1.88 ± 0.84 | 2.38 ± 0.83 | 2.54 ± 0.85 | 2.34 ± 0.89 | 2.15 ± 0.82 | 2.63 ± 0.84 | -0.86 ± 0.76 |
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.
| Millimoles per litre (mmol/L) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in Haematology: Haemoglobin | 0.01 ± 0.48 | -0.08 ± 0.65 | -0.02 ± 0.47 | -0.07 ± 0.51 | 0.00 ± 0.50 | -0.07 ± 0.47 | 0.02 ± 0.47 | 0.11 ± 0.48 | -0.01 ± 0.45 |
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.
| Percentage of red blood cells | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in Haematology: Haematocrit | -0.25 ± 2.48 | -0.58 ± 3.28 | -0.42 ± 2.26 | -0.49 ± 2.67 | -0.31 ± 2.75 | -0.68 ± 2.82 | -0.15 ± 2.67 | 0.26 ± 2.70 | 0.26 ± 2.44 |
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.
| 10^9 cells/litre (L) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Thrombocytes | -2.08 ± 35.26 | 2.95 ± 43.02 | -8.17 ± 42.59 | 2.79 ± 41.28 | -0.52 ± 39.59 | -5.76 ± 53.41 | -3.32 ± 45.02 | 4.83 ± 37.70 | -6.11 ± 39.11 |
| Leucocytes | -0.47 ± 1.38 | -0.24 ± 1.44 | -0.23 ± 1.81 | -0.50 ± 1.42 | -0.68 ± 1.41 | -0.66 ± 1.90 | -0.40 ± 1.43 | -0.17 ± 1.41 | -0.44 ± 1.62 |
| Eosinophils | 0.02 ± 0.11 | 0.02 ± 0.16 | -0.01 ± 0.09 | -0.02 ± 0.13 | 0.00 ± 0.08 | 0.01 ± 0.09 | -0.01 ± 0.08 | 0.01 ± 0.10 | 0.00 ± 0.08 |
| Neutrophils | -0.36 ± 1.17 | -0.07 ± 1.22 | -0.05 ± 1.62 | -0.22 ± 1.24 | -0.51 ± 1.27 | -0.57 ± 1.76 | -0.23 ± 1.19 | -0.12 ± 1.11 | -0.33 ± 1.28 |
| Basophils | 0.00 ± 0.03 | -0.00 ± 0.04 | -0.00 ± 0.03 | -0.01 ± 0.03 | -0.00 ± 0.03 | -0.01 ± 0.04 | 0.00 ± 0.04 | -0.00 ± 0.04 | 0.00 ± 0.04 |
| Monocytes | -0.04 ± 0.18 | -0.04 ± 0.12 | 0.01 ± 0.12 | -0.02 ± 0.10 | -0.02 ± 0.12 | -0.01 ± 0.13 | -0.03 ± 0.11 | -0.01 ± 0.14 | -0.02 ± 0.11 |
| Lymphocytes | -0.10 ± 0.36 | -0.16 ± 0.46 | -0.17 ± 0.38 | -0.24 ± 0.50 | -0.15 ± 0.36 | -0.08 ± 0.41 | -0.14 ± 0.37 | -0.06 ± 0.42 | -0.09 ± 0.66 |
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.
| 10^12 cells/litre (L) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in Haematology: Erythrocytes | -0.01 ± 0.26 | -0.06 ± 0.35 | -0.03 ± 0.27 | -0.04 ± 0.25 | -0.01 ± 0.29 | -0.04 ± 0.24 | -0.01 ± 0.27 | 0.05 ± 0.30 | 0.04 ± 0.24 |
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.
| Micromole/litre (umol/L) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Creatinine | -1.14 ± 6.53 | -0.85 ± 7.59 | -1.09 ± 6.11 | 0.76 ± 8.11 | 1.48 ± 29.73 | 1.05 ± 8.45 | -2.10 ± 8.49 | -0.81 ± 7.16 | 0.28 ± 8.06 |
| Bilirubin (total) | 0.30 ± 3.70 | 1.12 ± 3.60 | 1.59 ± 3.11 | 1.33 ± 3.61 | 1.23 ± 5.18 | 1.02 ± 4.04 | 1.67 ± 4.28 | 1.02 ± 3.67 | 1.09 ± 4.45 |
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.
| Unit/litre (U/L) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Creatinine kinase | 0.53 ± 68.43 | -44.75 ± 266.88 | -13.20 ± 44.33 | -46.34 ± 163.09 | -29.91 ± 95.05 | -8.86 ± 47.28 | -28.08 ± 122.61 | -3.09 ± 172.46 | 53.36 ± 571.63 |
| Amylase | 3.35 ± 13.82 | 4.84 ± 13.05 | 9.20 ± 12.72 | 7.53 ± 13.94 | 7.67 ± 16.26 | 8.39 ± 20.28 | 7.78 ± 14.82 | 7.12 ± 15.72 | 3.41 ± 12.27 |
| Lipase | 5.62 ± 32.22 | 8.83 ± 28.10 | 17.55 ± 41.20 | 13.28 ± 34.86 | 13.33 ± 17.92 | 14.92 ± 44.31 | 15.09 ± 36.28 | 11.86 ± 27.48 | 1.63 ± 11.57 |
| ALT | -5.82 ± 20.97 | -5.45 ± 12.64 | -7.44 ± 17.14 | -9.15 ± 23.09 | -3.64 ± 11.30 | -9.07 ± 20.96 | -7.17 ± 12.62 | -2.95 ± 14.19 | -3.03 ± 11.91 |
| AST | -1.08 ± 12.17 | -1.99 ± 7.95 | -2.33 ± 7.61 | -3.32 ± 10.22 | -2.07 ± 6.70 | -1.62 ± 10.78 | -2.73 ± 6.10 | -1.48 ± 10.13 | 0.00 ± 11.08 |
| ALP | -3.42 ± 13.04 | -3.44 ± 16.00 | -6.21 ± 10.96 | -6.70 ± 13.89 | -4.25 ± 12.65 | -3.50 ± 15.61 | -8.20 ± 14.13 | -0.52 ± 9.80 | -1.46 ± 11.39 |
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.
| Millimole/litre (mmol/L) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Urea | -0.04 ± 1.06 | 0.16 ± 1.26 | -0.01 ± 1.21 | -0.10 ± 1.25 | -0.00 ± 1.88 | -0.06 ± 1.33 | -0.33 ± 1.12 | 0.03 ± 1.06 | 0.21 ± 1.21 |
| Sodium | -0.18 ± 2.47 | -0.27 ± 1.77 | -0.40 ± 2.41 | -0.82 ± 2.36 | -0.92 ± 2.62 | -0.76 ± 3.49 | -0.74 ± 2.71 | -0.37 ± 2.08 | -0.35 ± 2.08 |
| Potassium | 0.01 ± 0.30 | 0.01 ± 0.38 | -0.00 ± 0.31 | -0.04 ± 0.36 | -0.10 ± 0.41 | 0.00 ± 0.36 | -0.11 ± 0.44 | -0.02 ± 0.35 | -0.04 ± 0.36 |
| Calcium (total) | 0.01 ± 0.07 | -0.01 ± 0.09 | 0.01 ± 0.08 | 0.01 ± 0.08 | 0.00 ± 0.09 | -0.00 ± 0.08 | 0.00 ± 0.09 | 0.02 ± 0.08 | -0.00 ± 0.08 |
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.
| Gram/decilitre (g/dL) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in Biochemistry: Albumin | 0.03 ± 0.18 | 0.01 ± 0.21 | 0.07 ± 0.20 | 0.05 ± 0.21 | 0.03 ± 0.22 | 0.01 ± 0.21 | 0.02 ± 0.23 | 0.06 ± 0.18 | 0.04 ± 0.20 |
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.
| Nanogram/litre (ng/L) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in Biochemistry: Calcitonin | 0.08 ± 0.71 | 0.03 ± 1.07 | 0.04 ± 0.44 | 0.04 ± 0.18 | 0.17 ± 0.79 | -0.01 ± 0.73 | 0.20 ± 0.72 | 0.29 ± 1.27 | -0.12 ± 2.16 |
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.
| Milli-international units/litre (mIU/L) | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Change in Biochemistry: TSH | -0.31 ± 1.62 | -0.10 ± 1.10 | -0.22 ± 0.85 | -0.18 ± 1.04 | -0.10 ± 0.96 | -0.12 ± 0.84 | -0.43 ± 1.01 | 0.02 ± 0.88 | -0.07 ± 0.97 |
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.
| Participants | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Wk 0: Suicidal ideation | 0 | 0 | 1 | 2 | 1 | 0 | 0 | 0 | 0 |
| Wk 0: Suicidal behaviour | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Wk 0: Non-suicidal self-injurious behaviour | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Wk 4-59: Suicidal ideation | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 2 | 1 |
| Wk 4-59: Suicidal behaviour | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Wk 4-59: Non-suicidal self-injurious behaviour | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
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.
| Score on a scale | 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 |
|---|---|---|---|---|---|---|---|---|---|
| Week 0 | 2.5 ± 3.4 | 1.7 ± 2.1 | 2.1 ± 2.6 | 1.5 ± 1.9 | 2.5 ± 2.9 | 1.7 ± 2.6 | 2.0 ± 2.2 | 2.0 ± 2.5 | 2.5 ± 3.1 |
| Week 52 | 1.5 ± 2.2 | 1.1 ± 1.8 | 1.3 ± 2.0 | 1.1 ± 1.7 | 1.0 ± 1.8 | 1.1 ± 1.4 | 0.9 ± 1.6 | 1.3 ± 2.0 | 1.7 ± 2.6 |
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.
| Participants | 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) |
|---|---|---|---|---|---|---|---|
| Anti-semaglutide Antibodies During and After Treatment | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Collected over Week 0 up to Week 59 (treatment period: week 0 to week 52 + follow-up period: week 53 to week 59).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Semaglutide 0.05 mg | 0/103 (0%) | 13/103 (12.6%) | 83/103 (80.6%) |
| Semaglutide 0.1 mg | 0/102 (0%) | 8/102 (7.8%) | 87/102 (85.3%) |
| Semaglutide 0.2 mg | 0/103 (0%) | 5/103 (4.9%) | 84/103 (81.6%) |
| Semaglutide 0.3 mg | 0/103 (0%) | 6/103 (5.8%) | 85/103 (82.5%) |
| Semaglutide 0.4 mg | 0/102 (0%) | 13/102 (12.7%) | 90/102 (88.2%) |
| Semaglutide 0.3 mg (Fast Escalation) | 0/102 (0%) | 6/102 (5.9%) | 91/102 (89.2%) |
| Semaglutide 0.4 mg (Fast Escalation) | 1/103 (1%) | 7/103 (6.8%) | 88/103 (85.4%) |
| Liraglutide 3.0 mg | 0/103 (0%) | 4/103 (3.9%) | 83/103 (80.6%) |
| Placebo Pool | 0/136 (0%) | 11/136 (8.1%) | 87/136 (64%) |
| Event | 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 |
|---|---|---|---|---|---|---|---|---|---|
| CholelithiasisHepatobiliary disorders | 0/103 | 0/102 | 1/103 | 0/103 | 1/102 | 3/102 | 1/103 | 0/103 | 0/136 |
| OsteoarthritisMusculoskeletal and connective tissue disorders | 3/103 | 0/102 | 0/103 | 1/103 | 0/102 | 0/102 | 0/103 | 0/103 | 0/136 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/103 | 2/102 | 0/103 | 1/103 | 0/102 | 0/102 | 0/103 | 0/103 | 0/136 |
| Pancreatitis acuteGastrointestinal disorders | 0/103 | 0/102 | 0/103 | 0/103 | 0/102 | 2/102 | 0/103 | 0/103 | 0/136 |
| ObesityMetabolism and nutrition disorders | 0/103 | 0/102 | 0/103 | 0/103 | 0/102 | 0/102 | 0/103 | 0/103 | 2/136 |
| Acute kidney injuryRenal and urinary disorders | 0/103 | 0/102 | 0/103 | 0/103 | 1/102 | 0/102 | 0/103 | 0/103 | 0/136 |
| Angina pectorisCardiac disorders | 0/103 | 0/102 | 0/103 | 0/103 | 1/102 | 0/102 | 0/103 | 0/103 | 0/136 |
| Angina unstableCardiac disorders | 0/103 | 0/102 | 0/103 | 0/103 | 1/102 | 0/102 | 0/103 | 0/103 | 0/136 |
| Cauda equina syndromeNervous system disorders | 0/103 | 0/102 | 0/103 | 0/103 | 1/102 | 0/102 | 0/103 | 0/103 | 0/136 |
| CellulitisInfections and infestations | 1/103 | 1/102 | 0/103 | 0/103 | 0/102 | 0/102 | 0/103 | 0/103 | 1/136 |
| Event | 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 |
|---|---|---|---|---|---|---|---|---|---|
| NauseaGastrointestinal disorders | 32/103 | 42/102 | 45/103 | 43/103 | 49/102 | 55/102 | 50/103 | 46/103 | 24/136 |
| DiarrhoeaGastrointestinal disorders | 20/103 | 25/102 | 35/103 | 27/103 | 38/102 | 28/102 | 28/103 | 29/103 | 16/136 |
| ConstipationGastrointestinal disorders | 13/103 | 22/102 | 26/103 | 18/103 | 24/102 | 19/102 | 29/103 | 24/103 | 6/136 |
| VomitingGastrointestinal disorders | 8/103 | 18/102 | 24/103 | 11/103 | 17/102 | 21/102 | 23/103 | 11/103 | 6/136 |
| NasopharyngitisInfections and infestations | 16/103 | 23/102 | 19/103 | 15/103 | 19/102 | 16/102 | 20/103 | 16/103 | 16/136 |
| HeadacheNervous system disorders | 7/103 | 15/102 | 10/103 | 10/103 | 20/102 | 14/102 | 11/103 | 15/103 | 15/136 |
| Decreased appetiteMetabolism and nutrition disorders | 8/103 | 17/102 | 13/103 | 13/103 | 14/102 | 18/102 | 20/103 | 12/103 | 5/136 |
| EructationGastrointestinal disorders | 4/103 | 8/102 | 14/103 | 8/103 | 7/102 | 17/102 | 10/103 | 6/103 | 1/136 |
| Abdominal painGastrointestinal disorders | 5/103 | 3/102 | 16/103 | 8/103 | 9/102 | 8/102 | 5/103 | 4/103 | 3/136 |
| DyspepsiaGastrointestinal disorders | 3/103 | 8/102 | 6/103 | 14/103 | 14/102 | 15/102 | 13/103 | 8/103 | 4/136 |
Overall number of baseline participants = full analysis set (FAS) which included all randomised participants. Number Analyzed = number of participants with available data.
| Age, Continuous(Years) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 46.97 ± 12.80 | 45.24 ± 12.62 | 44.37 ± 11.24 | 46.73 ± 12.02 | 48.37 ± 13.44 | 47.10 ± 12.05 | 46.07 ± 13.51 | 48.50 ± 11.22 | 46.42 ± 12.80 | 46.63 ± 12.46 |
| Sex: Female, Male(Participants) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Female | 67 | 66 | 66 | 66 | 66 | 66 | 67 | 67 | 88 | 619 |
| Male | 36 | 36 | 37 | 37 | 36 | 36 | 36 | 36 | 48 | 338 |
| Race/Ethnicity, Customized(Participants) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| White | 88 | 76 | 72 | 74 | 71 | 76 | 68 | 78 | 97 | 700 |
| Black or African American | 5 | 7 | 10 | 3 | 10 | 0 | 7 | 9 | 10 | 61 |
| Asian | 2 | 0 | 1 | 0 | 0 | 3 | 1 | 1 | 1 | 9 |
| American Indian or Alaska Native | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 3 |
| Other | 0 | 1 | 0 | 3 | 1 | 1 | 0 | 1 | 2 | 9 |
| Not applicable | 8 | 17 | 20 | 22 | 19 | 22 | 25 | 14 | 24 | 171 |
| Race/Ethnicity, Customized(Participants) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 3 | 7 | 6 | 13 | 4 | 6 | 3 | 6 | 7 | 55 |
| Not Hispanic or Latino | 96 | 86 | 93 | 79 | 90 | 82 | 91 | 93 | 117 | 827 |
| Not applicable | 4 | 9 | 4 | 11 | 8 | 14 | 9 | 4 | 12 | 75 |
| Body weight(Kilogram (Kg)) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 111.29 ± 23.17 | 111.31 ± 21.47 | 114.49 ± 24.53 | 111.51 ± 22.96 | 113.20 ± 26.42 | 108.11 ± 22.08 | 109.56 ± 21.33 | 108.71 ± 21.94 | 114.19 ± 25.37 | 111.48 ± 23.39 |
| Glycosylated haemoglobin (HbA1c)(Percentage (%) of HbA1c) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 5.51 ± 0.35 | 5.45 ± 0.43 | 5.41 ± 0.39 | 5.51 ± 0.38 | 5.47 ± 0.42 | 5.48 ± 0.41 | 5.49 ± 0.42 | 5.53 ± 0.38 | 5.54 ± 0.38 | 5.49 ± 0.40 |
| Fasting plasma glucose (FPG)(Millimoles per litre (mmol/L)) | 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 5.48 ± 0.64 | 5.48 ± 0.55 | 5.41 ± 0.77 | 5.48 ± 0.73 | 5.40 ± 0.67 | 5.43 ± 0.64 | 5.54 ± 0.87 | 5.55 ± 0.73 | 5.50 ± 0.62 | 5.48 ± 0.69 |
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