Obesity, Overweight
Conditions
Brief summary
This study will look at the change in participant's body weight from the start to the end of the study. This is to compare the effect on body weight in people taking semaglutide (a new medicine) and people taking dummy medicine. Together with the medicine, the participant will also be part of an intensive lifestyle program where the participant will have talks with study staff about healthy food choices, what the participant can do to lose weight and be more physically active. The participant will either get semaglutide or dummy medicine - which treatment the participant gets is decided by chance. The participant will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. For the first 2 months the participant will be on a low calorie diet. The diet is made up of bars, shakes and 1 low calorie pre-prepared meal for each day. The study will last for about 1.5 years. The participant will have 32 clinic visits with the study doctor.
Interventions
DRUGSemaglutide
Subcutaneous (s.c., under the skin) injections of semaglutide once weekly at escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks.
DRUGPlacebo (semaglutide)
S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, age more than or equal to 18 years at the time of signing informed consent * Body mass index more than or equal to 30 kg/m\^2 or more than or equal to 27 kg/m\^2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease * History of at least one self-reported unsuccessful dietary effort to lose body weight
Exclusion criteria
* Hemoglobin A1c more than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening * A self-reported change in body weight more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight (%) | Baseline (week 0) to week 68 | Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period). |
| Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% | After 68 weeks | Number of participants who achieved greater than or equal to (≥) 5% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 5% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 5% weight loss. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20% | After 68 weeks | Number of participants who achieved greater than or equal to (≥) 20% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 20% weight loss whereas 'No' infers number of participants who have not achieved ≥ 20% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). |
| Change in Waist Circumference | Baseline (week 0) to week 68 | Change in waist circumference from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Systolic Blood Pressure | Baseline (week 0) to week 68 | Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Short Form-36 (SF-36) - Physical Functioning Score | Baseline (week 0) to week 68 | 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™ questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). The 0-100 scale scores 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. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Body Weight (Kg) | Baseline (week 0) to week 68 | Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Body Mass Index | Baseline (week 0) to week 68 | Change in body mass index from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in HbA1c (%) | Baseline (week 0) to week 68 | Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in HbA1c (mmol/Mol) | Baseline (week 0) to week 68 | Change in HbA1c from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Fasting Plasma Glucose | Baseline (week 0) to week 68 | Change in fasting plasma glucose from week 0 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Fasting Serum Insulin | Baseline (week 0) to week 68 | Change in fasting serum insulin from week 0 to week 68 \[measured as milli-international units per milliliter (mIU/mL)\] is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Diastolic Blood Pressure | Baseline (week 0) to week 68 | Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Total Cholesterol | Baseline (week 0) to week 68 | Change in fasting total cholesterol from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Triglycerides | Baseline (week 0) to week 68 | Change in fasting triglycerides from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10% | After 68 weeks | Number of participants who achieved greater than or equal to (≥) 10% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 10% weight loss whereas 'No' infers number of participants who have not achieved ≥ 10% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). |
| Change in Low-density Lipoproteins (LDL) | Baseline (week 0) to week 68 | Change in fasting LDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Very Low Density Lipoprotein (VLDL) | Baseline (week 0) to week 68 | Change in fasting VLDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Free Fatty Acids | Baseline (week 0) to week 68 | Change in fasting free fatty acids from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in High Sensitivity C-reactive Protein | Baseline (week 0) to week 68 | Change in high sensitivity C-reactive protein from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Change in Plasminogen Activator Inhibitor-1 Activity | Baseline (week 0) to week 68 | Change in plasminogen activator inhibitor-1 activity from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | After 68 weeks | The observed number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on two thresholds. The threshold of 4.3 is the default generic responder threshold defined in SF-36 manual for a general population. The threshold of 3.7 is specific for overweight or obese population included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on Food and Drug Administration (FDA) recommendations. In the reported data, Yes infers number of participants who have achieved an improvement in score greater than or equal to the threshold and No infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on the in-trial observation period which is uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75). |
| Change in Body Weight | Baseline (week 0) to week 8 | Change in body weight from baseline (week 0) to week 8 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Number of Treatment-emergent Adverse Events (AEs) | Baseline (week 0) to week 75 | An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period). |
| Number of Serious Adverse Events (SAEs) | Baseline (week 0) to week 75 | A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. The SAEs occurred from week 0 to week 75 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period). |
| Change in Pulse | Baseline (week 0) to week 68 | Change in pulse from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period). |
| Change in Amylase | Baseline (week 0) to week 68 | Change in amylase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period). |
| Change in Lipase | Baseline (week 0) to week 68 | Change in lipase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period). |
| Change in Calcitonin | Baseline (week 0) to week 68 | Change in calcitonin (measured as ng/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period). |
| Change in High-density Lipoproteins (HDL) | Baseline (week 0) to week 68 | Change in fasting HDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline.The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75). |
| Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15% | After 68 weeks | Number of participants who achieved greater than or equal to (≥) 15% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 15% weight loss whereas 'No' infers number of participants who have not achieved ≥ 15% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). |
Countries
United States
Participant flow
Recruitment details
The trial was conducted in 41 sites in the United States.
Pre-assignment details
The trial has a 68-week treatment period (16 weeks of dose escalation and 52 weeks of maintenance dose). Participants were randomised in 2:1 ratio either to receive semaglutide 2.4 mg or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide 2.4 mg Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment. | 407 |
| Placebo Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment. | 204 |
| Total | 611 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 26 | 6 |
| Overall Study | At the discretion of the investigator | 1 | 0 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 18 | 7 |
| Overall Study | other | 17 | 16 |
| Overall Study | Pregnancy | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Safety concern as judged by the investigator | 1 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Placebo | Total | Semaglutide 2.4 mg |
|---|---|---|---|
| Age, Continuous | 46 Years STANDARD_DEVIATION 13 | 46 Years STANDARD_DEVIATION 13 | 46 Years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 46 Participants | 121 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 158 Participants | 490 Participants | 332 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 36 Participants | 116 Participants | 80 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 15 Participants | 11 Participants |
| Race (NIH/OMB) White | 158 Participants | 465 Participants | 307 Participants |
| Sex: Female, Male Female | 180 Participants | 495 Participants | 315 Participants |
| Sex: Female, Male Male | 24 Participants | 116 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 407 | 0 / 204 |
| other Total, other adverse events | 379 / 407 | 177 / 204 |
| serious Total, serious adverse events | 37 / 407 | 6 / 204 |
Outcome results
Primary
Change in Body Weight (%)
Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time frame: Baseline (week 0) to week 68
Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 2.4 mg | Change in Body Weight (%) | In-trial observation period | -16.5 Percentage | Standard Deviation 10.1 |
| Semaglutide 2.4 mg | Change in Body Weight (%) | On-treatment observation period | -17.6 Percentage | Standard Deviation 9.6 |
| Placebo | Change in Body Weight (%) | In-trial observation period | -5.8 Percentage | Standard Deviation 7.7 |
| Placebo | Change in Body Weight (%) | On-treatment observation period | -6.1 Percentage | Standard Deviation 7.6 |
Comparison: Treatment policy estimandp-value: <0.000195% CI: [-11.97, -8.57]ANCOVA
Comparison: Hypothetical estimandp-value: <0.000195% CI: [-14.34, -11]MMRM (mixed model repeated measurement)
Primary
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%
Number of participants who achieved greater than or equal to (≥) 5% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 5% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 5% weight loss. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption.
Time frame: After 68 weeks
Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% | In-trial observation period | Yes | 323 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% | In-trial observation period | No | 50 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% | On-treatment observation period | Yes | 300 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% | On-treatment observation period | No | 34 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% | On-treatment observation period | No | 82 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% | In-trial observation period | Yes | 90 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% | On-treatment observation period | Yes | 82 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% | In-trial observation period | No | 99 Participants |
Comparison: Treatment policy estimandp-value: <0.000195% CI: [4.04, 9.26]Regression, Logistic
Comparison: Hypothetical estimandp-value: <0.000195% CI: [7.64, 17.81]MMRM (mixed model repeated measurement)
Secondary
Change in Amylase
Change in amylase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time frame: Baseline (week 0) to week 68
Population: SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Amylase | 1.12 Ratio of amylase | Geometric Coefficient of Variation 19 |
| Placebo | Change in Amylase | 1.07 Ratio of amylase | Geometric Coefficient of Variation 18.1 |
Secondary
Change in Body Mass Index
Change in body mass index from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Body Mass Index | -6.2 Kilogram per square meter (kg/sqm) | Standard Deviation 4 |
| Placebo | Change in Body Mass Index | -2.2 Kilogram per square meter (kg/sqm) | Standard Deviation 3.1 |
Secondary
Change in Body Weight
Change in body weight from baseline (week 0) to week 8 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 8
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Body Weight | -7.8 Percentage | Standard Deviation 3.1 |
| Placebo | Change in Body Weight | -6.0 Percentage | Standard Deviation 3.6 |
Secondary
Change in Body Weight (Kg)
Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Body Weight (Kg) | -17.5 Kilogram (kg) | Standard Deviation 11.4 |
| Placebo | Change in Body Weight (Kg) | -6.2 Kilogram (kg) | Standard Deviation 8.6 |
Secondary
Change in Calcitonin
Change in calcitonin (measured as ng/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time frame: Baseline (week 0) to week 68
Population: SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Calcitonin | 0.93 Ratio of calcitonin | Geometric Coefficient of Variation 40.6 |
| Placebo | Change in Calcitonin | 0.94 Ratio of calcitonin | Geometric Coefficient of Variation 33.2 |
Secondary
Change in Diastolic Blood Pressure
Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Diastolic Blood Pressure | -3 mmHg | Standard Deviation 10 |
| Placebo | Change in Diastolic Blood Pressure | -1 mmHg | Standard Deviation 10 |
Secondary
Change in Fasting Plasma Glucose
Change in fasting plasma glucose from week 0 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Fasting Plasma Glucose | -7.3 milligrams per deciliter (mg/dL) | Standard Deviation 10.9 |
| Placebo | Change in Fasting Plasma Glucose | -1.1 milligrams per deciliter (mg/dL) | Standard Deviation 10.6 |
Secondary
Change in Fasting Serum Insulin
Change in fasting serum insulin from week 0 to week 68 \[measured as milli-international units per milliliter (mIU/mL)\] is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Fasting Serum Insulin | 0.68 Ratio of fasting serum insulin | Geometric Coefficient of Variation 67.4 |
| Placebo | Change in Fasting Serum Insulin | 0.84 Ratio of fasting serum insulin | Geometric Coefficient of Variation 50.6 |
Secondary
Change in Free Fatty Acids
Change in fasting free fatty acids from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Free Fatty Acids | 0.86 Ratio of fasting free fatty acids | Geometric Coefficient of Variation 69.9 |
| Placebo | Change in Free Fatty Acids | 1.08 Ratio of fasting free fatty acids | Geometric Coefficient of Variation 71.8 |
Secondary
Change in HbA1c (%)
Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in HbA1c (%) | -0.5 Percentage point of HbA1c | Standard Deviation 0.3 |
| Placebo | Change in HbA1c (%) | -0.3 Percentage point of HbA1c | Standard Deviation 0.2 |
Secondary
Change in HbA1c (mmol/Mol)
Change in HbA1c from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in HbA1c (mmol/Mol) | -5.8 mmol/mol | Standard Deviation 3.1 |
| Placebo | Change in HbA1c (mmol/Mol) | -3.1 mmol/mol | Standard Deviation 2.5 |
Secondary
Change in High-density Lipoproteins (HDL)
Change in fasting HDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline.The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in High-density Lipoproteins (HDL) | 1.06 Ratio of fasting HDL cholesterol | Geometric Coefficient of Variation 14.6 |
| Placebo | Change in High-density Lipoproteins (HDL) | 1.05 Ratio of fasting HDL cholesterol | Geometric Coefficient of Variation 15 |
Secondary
Change in High Sensitivity C-reactive Protein
Change in high sensitivity C-reactive protein from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in High Sensitivity C-reactive Protein | 0.40 milligrams per litre (mg/L) | Geometric Coefficient of Variation 108.7 |
| Placebo | Change in High Sensitivity C-reactive Protein | 0.76 milligrams per litre (mg/L) | Geometric Coefficient of Variation 75.5 |
Secondary
Change in Lipase
Change in lipase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time frame: Baseline (week 0) to week 68
Population: SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Lipase | 1.31 Ratio of lipase | Geometric Coefficient of Variation 52 |
| Placebo | Change in Lipase | 0.94 Ratio of lipase | Geometric Coefficient of Variation 39.4 |
Secondary
Change in Low-density Lipoproteins (LDL)
Change in fasting LDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Low-density Lipoproteins (LDL) | 0.96 Ratio of fasting LDL cholesterol | Geometric Coefficient of Variation 23.2 |
| Placebo | Change in Low-density Lipoproteins (LDL) | 1.01 Ratio of fasting LDL cholesterol | Geometric Coefficient of Variation 18.6 |
Secondary
Change in Plasminogen Activator Inhibitor-1 Activity
Change in plasminogen activator inhibitor-1 activity from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Plasminogen Activator Inhibitor-1 Activity | 0.92 Arbritary units per milliliter (AU/ml) | Geometric Coefficient of Variation 80.6 |
| Placebo | Change in Plasminogen Activator Inhibitor-1 Activity | 1.26 Arbritary units per milliliter (AU/ml) | Geometric Coefficient of Variation 74.2 |
Secondary
Change in Pulse
Change in pulse from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time frame: Baseline (week 0) to week 68
Population: SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Pulse | 3 beats per minute (bpm) | Standard Deviation 11 |
| Placebo | Change in Pulse | 2 beats per minute (bpm) | Standard Deviation 10 |
Secondary
Change in Short Form-36 (SF-36) - Physical Functioning Score
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™ questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). The 0-100 scale scores 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. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 2.4 mg | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in physical functioning score (SF-36) | 2.5 Score on a scale | Standard Deviation 5.7 |
| Semaglutide 2.4 mg | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Role-Physical score | 1.6 Score on a scale | Standard Deviation 6.5 |
| Semaglutide 2.4 mg | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Bodily Pain score | 1.3 Score on a scale | Standard Deviation 7.1 |
| Semaglutide 2.4 mg | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: General Health score | 3.4 Score on a scale | Standard Deviation 6.6 |
| Semaglutide 2.4 mg | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Vitality score | 2.0 Score on a scale | Standard Deviation 8.2 |
| Semaglutide 2.4 mg | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Social Functioning score | 0.1 Score on a scale | Standard Deviation 6.6 |
| Semaglutide 2.4 mg | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Mental Health score | -0.5 Score on a scale | Standard Deviation 6 |
| Semaglutide 2.4 mg | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Physical component summary | 3.2 Score on a scale | Standard Deviation 6 |
| Semaglutide 2.4 mg | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Mental component summary | -0.9 Score on a scale | Standard Deviation 6 |
| Semaglutide 2.4 mg | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Role-Emotional score | -0.6 Score on a scale | Standard Deviation 5.6 |
| Placebo | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Physical component summary | 2.6 Score on a scale | Standard Deviation 6.5 |
| Placebo | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in physical functioning score (SF-36) | 1.7 Score on a scale | Standard Deviation 5.7 |
| Placebo | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Social Functioning score | -1.2 Score on a scale | Standard Deviation 8 |
| Placebo | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Role-Physical score | 1.5 Score on a scale | Standard Deviation 6.7 |
| Placebo | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Role-Emotional score | -1.5 Score on a scale | Standard Deviation 7.7 |
| Placebo | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Bodily Pain score | 0.6 Score on a scale | Standard Deviation 8.3 |
| Placebo | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Mental Health score | -1.5 Score on a scale | Standard Deviation 7.1 |
| Placebo | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: General Health score | 1.9 Score on a scale | Standard Deviation 6.4 |
| Placebo | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Mental component summary | -2.2 Score on a scale | Standard Deviation 8 |
| Placebo | Change in Short Form-36 (SF-36) - Physical Functioning Score | Change in SF-36: Vitality score | 0.9 Score on a scale | Standard Deviation 7.8 |
Secondary
Change in Systolic Blood Pressure
Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Systolic Blood Pressure | -6 Millimeters of mercury (mmHg) | Standard Deviation 14 |
| Placebo | Change in Systolic Blood Pressure | -2 Millimeters of mercury (mmHg) | Standard Deviation 15 |
Secondary
Change in Total Cholesterol
Change in fasting total cholesterol from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Total Cholesterol | 0.96 Ratio of fasting total cholesterol | Geometric Coefficient of Variation 15 |
| Placebo | Change in Total Cholesterol | 1.01 Ratio of fasting total cholesterol | Geometric Coefficient of Variation 12.3 |
Secondary
Change in Triglycerides
Change in fasting triglycerides from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Triglycerides | 0.77 Ratio of fasting triglycerides | Geometric Coefficient of Variation 41.3 |
| Placebo | Change in Triglycerides | 0.91 Ratio of fasting triglycerides | Geometric Coefficient of Variation 39.1 |
Secondary
Change in Very Low Density Lipoprotein (VLDL)
Change in fasting VLDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Very Low Density Lipoprotein (VLDL) | 0.77 Ratio of fasting VLDL cholesterol | Geometric Coefficient of Variation 40.9 |
| Placebo | Change in Very Low Density Lipoprotein (VLDL) | 0.91 Ratio of fasting VLDL cholesterol | Geometric Coefficient of Variation 38.6 |
Secondary
Change in Waist Circumference
Change in waist circumference from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Waist Circumference | -15.2 Centimeter (cm) | Standard Deviation 10.2 |
| Placebo | Change in Waist Circumference | -6.1 Centimeter (cm) | Standard Deviation 8.6 |
Secondary
Number of Serious Adverse Events (SAEs)
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. The SAEs occurred from week 0 to week 75 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).
Time frame: Baseline (week 0) to week 75
Population: SAS included all participants who received at least one dose of trial product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 2.4 mg | Number of Serious Adverse Events (SAEs) | 55 events |
| Placebo | Number of Serious Adverse Events (SAEs) | 7 events |
Secondary
Number of Treatment-emergent Adverse Events (AEs)
An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).
Time frame: Baseline (week 0) to week 75
Population: SAS included all participants who received at least one dose of trial product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 2.4 mg | Number of Treatment-emergent Adverse Events (AEs) | 4035 events |
| Placebo | Number of Treatment-emergent Adverse Events (AEs) | 1325 events |
Secondary
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10%
Number of participants who achieved greater than or equal to (≥) 10% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 10% weight loss whereas 'No' infers number of participants who have not achieved ≥ 10% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time frame: After 68 weeks
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10% | Yes | 281 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10% | No | 92 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10% | Yes | 51 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10% | No | 138 Participants |
Secondary
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15%
Number of participants who achieved greater than or equal to (≥) 15% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 15% weight loss whereas 'No' infers number of participants who have not achieved ≥ 15% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time frame: After 68 weeks
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15% | Yes | 208 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15% | No | 165 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15% | Yes | 25 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15% | No | 164 Participants |
Secondary
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20%
Number of participants who achieved greater than or equal to (≥) 20% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 20% weight loss whereas 'No' infers number of participants who have not achieved ≥ 20% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time frame: After 68 weeks
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20% | Yes | 133 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20% | No | 240 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20% | Yes | 7 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20% | No | 182 Participants |
Secondary
Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score
The observed number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on two thresholds. The threshold of 4.3 is the default generic responder threshold defined in SF-36 manual for a general population. The threshold of 3.7 is specific for overweight or obese population included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on Food and Drug Administration (FDA) recommendations. In the reported data, Yes infers number of participants who have achieved an improvement in score greater than or equal to the threshold and No infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on the in-trial observation period which is uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).
Time frame: After 68 weeks
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Yes (with threshold 4.3) | 86 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No (with threshold 4.3) | 278 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Yes (with threshold 3.7) | 133 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No (with threshold 3.7) | 231 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No (with threshold 3.7) | 130 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Yes (with threshold 4.3) | 36 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Yes (with threshold 3.7) | 51 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No (with threshold 4.3) | 145 Participants |