Metabolism and Nutrition Disorder, Obesity
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. In addition to taking the medicine, the participant will have talks with study staff about healthy food choices, how to be more physically active and what a participant can do to lose weight. The participant will get semaglutide for the first 20 weeks. Then the participant will get either semaglutide or dummy medicine - which treatment the participant gets after the 20 weeks is decided by chance. The participants 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. The study will last for about 1.5 years.
Interventions
DRUGSemaglutide
Subcutaneous (under the skin) injection of semaglutide once-weekly.
DRUGPlacebo
Subcutaneous (under the skin) injection of semaglutide placebo once-weekly.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, age greater than or equal to 18 years at the time of signing informed consent * Body mass index greater than or equal to 30 kg/sqm or greater than or equal to 27 kg/sqm 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
* Haemoglobin A1c greater than or equal to 48 mmol/mol (6.5%) as measured by 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 From Randomisation to Week 68 in Body Weight (%) | Randomisation (week 20) to week 68 | Change in body weight from baseline (week 20) to week 68 is presented. 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 run-in (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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systolic Blood Pressure | Randomization (week 20) to week 68 | Change in systolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Diastolic Blood Pressure | Randomization (week 20) to week 68 | Change in diastolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Physical Functioning Score (Short Form 36 [SF-36]) | Randomization (week 20) 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 20 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Body Weight [Kilogram (Kg)] | Randomisation (week 20) to week 68 | Change in body weight from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Body Mass Index (BMI) | Randomization (week 20) to week 68 | Change in BMI from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Haemoglobin A1c (HbA1c) [%] | Randomization (week 20) to week 68 | Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in HbA1c [Millimoles Per Mole (mmol/Mol)] | Randomization (week 20) to week 68 | Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)] | Randomization (week 20) to week 68 | Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)] | Randomization (week 20) to week 68 | Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Fasting Serum Insulin | Randomization (week 20) to week 68 | Change in fasting serum insulin from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Total Cholesterol | Randomization (week 20) to week 68 | Change in fasting total cholesterol from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in High-density Lipoproteins (HDL) | Randomization (week 20) to week 68 | Change in fasting HDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Low-density Lipoproteins (LDL) | Randomization (week 20) to week 68 | Change in fasting LDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Very Low-density Lipoproteins (VLDL) | Randomization (week 20) to week 68 | Change in fasting VLDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Free Fatty Acids | Randomization (week 20) to week 68 | Change in fasting free fatty acids from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Waist Circumference | Randomization (week 20) to week 68 | Change in waist circumference from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Randomisation (week 20) to week 68 | The number of participants achieving at least a 4.3-point increase in SF-36 physical functioning score from baseline (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved 4.3 points of increase of the score and 'No' infers number of participants who have not achieved 4.3 points of increase of the score. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75). |
| Subjects Who Gain Weight (Yes/no) | Randomisation (week 20) to week 68 | The number of participants with weight gain from the start of the randomised period (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have gained weight and 'No' infers number of participants who have not gained weight. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75). |
| Change in Body Weight | Run-in (week 0) to week 68 | The body weight change (%) 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Subjects Who Achieve (Yes/no): Body Weight Reduction < 0% | Run-in (week 0) to week 68 | The number of participants who achieved less than (\<) 0% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved \<0% weight loss whereas 'No' infers number of participants who have not achieved \<0% 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5% | Run-in (week 0) to week 68 | The number of participants who achieved greater than or equal to (≥) 5% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 5% weight loss whereas 'No' infers number of participants who have not achieved ≥ 5% 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10% | Run-in (week 0) to week 68 | The number of participants who achieved ≥ 10% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15% | Run-in (week 0) to week 68 | The number of participants who achieved ≥ 15% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
| Number of Treatment-emergent Adverse Events (AEs) | Run-in (week 0) to randomisation (week 20) | 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 (week 0-20 run-in period). 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 Treatment-emergent AEs | Randomisation (week 20) to week 75 | An 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 TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment (week 20-75). 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) | Run-in (week 0) to randomisation (week 20) | 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 during run-in period from week 0 to week 20 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 | Run-in (week 0) to randomisation (week 20) | Change in pulse rate from week 0 week to week 20 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 | Run-in (week) 0 to randomization (week 20) | Change in amylase (measured as units per liter \[U/L\]) 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 | Run-in (week 0) to randomization (week 20) | 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 | Run-in (week 0) to randomization (week 20) | Change in calcitonin (measured as nanogram per liter (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 Triglycerides | Randomization (week 20) to week 68 | Change in fasting triglycerides from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75). |
Countries
Denmark, Israel, Netherlands, Portugal, South Africa, Spain, Sweden, Switzerland, Ukraine, United States
Participant flow
Recruitment details
The trial was conducted in 73 sites in Denmark (2), Israel (6), Netherlands (3), Portugal (6), South Africa (6), Spain (7), Sweden (4), Switzerland (6), Ukraine (5) and United States (28).
Pre-assignment details
The trial included 20-week run-in period and 48-week maintenance period. During the run-in period, participant started with a semaglutide dose of 0.25 mg and the dose was increased every fourth week until the target dose, 2.4 mg was reached. Out of 902 participants, 803 have completed the run-in period. Thus, these were randomised in 2:1 ratio either to receive semaglutide 2.4 mg or placebo. The treatment is an adjunct to reduced-calorie diet and increased physical activity.
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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68. | 535 |
| Placebo Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68. | 268 |
| Total | 803 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Maintenance Period (Week 20 to Week 68) | Adverse Event | 13 | 6 |
| Maintenance Period (Week 20 to Week 68) | Lost to Follow-up | 2 | 1 |
| Maintenance Period (Week 20 to Week 68) | other | 12 | 23 |
| Maintenance Period (Week 20 to Week 68) | Pregnancy | 2 | 0 |
| Maintenance Period (Week 20 to Week 68) | Protocol Violation | 1 | 0 |
| Maintenance Period (Week 20 to Week 68) | Withdrawal by Subject | 1 | 1 |
| Run-in Period (Week 0 to Week 20) | Adverse Event | 48 | 0 |
| Run-in Period (Week 0 to Week 20) | Lost to Follow-up | 8 | 0 |
| Run-in Period (Week 0 to Week 20) | Other | 9 | 0 |
| Run-in Period (Week 0 to Week 20) | Pregnancy | 1 | 0 |
| Run-in Period (Week 0 to Week 20) | Protocol Violation | 1 | 0 |
| Run-in Period (Week 0 to Week 20) | Run-in failure | 19 | 0 |
| Run-in Period (Week 0 to Week 20) | Safety concern as judged by investigator | 2 | 0 |
| Run-in Period (Week 0 to Week 20) | Withdrawal by Subject | 11 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Semaglutide 2.4 mg |
|---|---|---|---|
| Age, Continuous | 46 Years STANDARD_DEVIATION 12 | 46 Years STANDARD_DEVIATION 12 | 47 Years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 63 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 247 Participants | 740 Participants | 493 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 19 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 35 Participants | 104 Participants | 69 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) White | 226 Participants | 672 Participants | 446 Participants |
| Sex: Female, Male Female | 205 Participants | 634 Participants | 429 Participants |
| Sex: Female, Male Male | 63 Participants | 169 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 902 | 1 / 535 | 1 / 268 |
| other Total, other adverse events | 670 / 902 | 295 / 535 | 114 / 268 |
| serious Total, serious adverse events | 21 / 902 | 41 / 535 | 15 / 268 |
Outcome results
Primary
Change From Randomisation to Week 68 in Body Weight (%)
Change in body weight from baseline (week 20) to week 68 is presented. 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 run-in (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: Randomisation (week 20) to week 68
Population: Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 2.4 mg | Change From Randomisation to Week 68 in Body Weight (%) | In-trial | -8.3 Percentage point | Standard Deviation 8.1 |
| Semaglutide 2.4 mg | Change From Randomisation to Week 68 in Body Weight (%) | On-treatment | -8.8 Percentage point | Standard Deviation 7.8 |
| Placebo | Change From Randomisation to Week 68 in Body Weight (%) | In-trial | 6.5 Percentage point | Standard Deviation 7.7 |
| Placebo | Change From Randomisation to Week 68 in Body Weight (%) | On-treatment | 6.1 Percentage point | Standard Deviation 7.7 |
Comparison: Treatment policy estimandp-value: <0.000195% CI: [-16, -13.5]ANCOVA
Comparison: Hypothetical estimandp-value: <0.000195% CI: [-16.52, -14.13]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: Randomisation (week 20) to week 68
Population: SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Amylase | 1.06 Ratio of amylase | Geometric Coefficient of Variation 19.9 |
| Placebo | Change in Amylase | 1.00 Ratio of amylase | Geometric Coefficient of Variation 24.9 |
Secondary
Change in Amylase
Change in amylase (measured as units per liter \[U/L\]) 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: Run-in (week) 0 to randomization (week 20)
Population: SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Amylase | 1.06 Ratio of amylase | Geometric Coefficient of Variation 18.7 |
| Placebo | Change in Amylase | 1.02 Ratio of amylase | Geometric Coefficient of Variation 26.2 |
Secondary
Change in Body Mass Index (BMI)
Change in BMI from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 Mass Index (BMI) | -2.7 Kilogram per square meter (kg/sqm) | Standard Deviation 2.7 |
| Placebo | Change in Body Mass Index (BMI) | 2.0 Kilogram per square meter (kg/sqm) | Standard Deviation 2.4 |
Secondary
Change in Body Weight
The body weight change (%) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Run-in (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 | -17.7 Percentage point | Standard Deviation 9.8 |
| Placebo | Change in Body Weight | -5.4 Percentage point | Standard Deviation 7.3 |
Secondary
Change in Body Weight [Kilogram (Kg)]
Change in body weight from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomisation (week 20) 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 [Kilogram (Kg)] | -7.5 Kg | Standard Deviation 7.6 |
| Placebo | Change in Body Weight [Kilogram (Kg)] | 5.7 Kg | Standard Deviation 6.7 |
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: Randomisation (week 20) to week 68
Population: SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Calcitonin | 1.00 Ratio of Calcitonin | Geometric Coefficient of Variation 24.8 |
| Placebo | Change in Calcitonin | 0.95 Ratio of Calcitonin | Geometric Coefficient of Variation 25.5 |
Secondary
Change in Calcitonin
Change in calcitonin (measured as nanogram per liter (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: Run-in (week 0) to randomization (week 20)
Population: SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Calcitonin | 0.98 Ratio of Calcitonin | Geometric Coefficient of Variation 28.4 |
| Placebo | Change in Calcitonin | 0.96 Ratio of Calcitonin | Geometric Coefficient of Variation 28.1 |
Secondary
Change in Diastolic Blood Pressure
Change in diastolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 | 0 mmHg | Standard Deviation 9 |
| Placebo | Change in Diastolic Blood Pressure | 1 mmHg | Standard Deviation 9 |
Secondary
Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)]
Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 [Milligrams Per Deciliter (mg/dL)] | -1.1 mg/dL | Standard Deviation 8.6 |
| Placebo | Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)] | 7.6 mg/dL | Standard Deviation 10 |
Secondary
Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)]
Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 [Millimoles Per Litre (mmol/L)] | -0.1 mmol/L | Standard Deviation 0.5 |
| Placebo | Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)] | 0.4 mmol/L | Standard Deviation 0.6 |
Secondary
Change in Fasting Serum Insulin
Change in fasting serum insulin from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 | 0.81 Ratio of fasting serum insulin | Geometric Coefficient of Variation 60.9 |
| Placebo | Change in Fasting Serum Insulin | 1.03 Ratio of fasting serum insulin | Geometric Coefficient of Variation 64.6 |
Secondary
Change in Free Fatty Acids
Change in fasting free fatty acids from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 | 0.78 Ratio of fasting free fatty acids | Geometric Coefficient of Variation 79.4 |
| Placebo | Change in Free Fatty Acids | 0.89 Ratio of fasting free fatty acids | Geometric Coefficient of Variation 73.1 |
Secondary
Change in Haemoglobin A1c (HbA1c) [%]
Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 Haemoglobin A1c (HbA1c) [%] | -0.2 Percentage point of HbA1c | Standard Deviation 0.3 |
| Placebo | Change in Haemoglobin A1c (HbA1c) [%] | 0.1 Percentage point of HbA1c | Standard Deviation 0.2 |
Secondary
Change in HbA1c [Millimoles Per Mole (mmol/Mol)]
Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 [Millimoles Per Mole (mmol/Mol)] | -1.7 mmol/mol | Standard Deviation 2.8 |
| Placebo | Change in HbA1c [Millimoles Per Mole (mmol/Mol)] | 1.2 mmol/mol | Standard Deviation 2.7 |
Secondary
Change in High-density Lipoproteins (HDL)
Change in fasting HDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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) | 1.18 Ratio of fasting HDL cholesterol | Geometric Coefficient of Variation 13.2 |
| Placebo | Change in High-density Lipoproteins (HDL) | 1.18 Ratio of fasting HDL cholesterol | Geometric Coefficient of Variation 16.3 |
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: Run-in (week 0) to randomization (week 20)
Population: SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Lipase | 1.44 Ratio of lipase | Geometric Coefficient of Variation 40.2 |
| Placebo | Change in Lipase | 1.39 Ratio of lipase | Geometric Coefficient of Variation 53.5 |
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: Randomisation (week 20) to week 68
Population: SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Lipase | 0.94 ratio of lipase | Geometric Coefficient of Variation 37.8 |
| Placebo | Change in Lipase | 0.68 ratio of lipase | Geometric Coefficient of Variation 51.7 |
Secondary
Change in Low-density Lipoproteins (LDL)
Change in fasting LDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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) | 1.01 Ratio of fasting LDL cholesterol | Geometric Coefficient of Variation 19.8 |
| Placebo | Change in Low-density Lipoproteins (LDL) | 1.07 Ratio of fasting LDL cholesterol | Geometric Coefficient of Variation 21.3 |
Secondary
Change in Physical Functioning Score (Short Form 36 [SF-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™ 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 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 2.4 mg | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in physical functioning score (SF-36) | 1.0 Scores on a scale | Standard Deviation 3.8 |
| Semaglutide 2.4 mg | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 role-physical score | 0.3 Scores on a scale | Standard Deviation 5 |
| Semaglutide 2.4 mg | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 bodily pain score | 0.5 Scores on a scale | Standard Deviation 7 |
| Semaglutide 2.4 mg | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 general health score | 0.3 Scores on a scale | Standard Deviation 5.2 |
| Semaglutide 2.4 mg | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 vitality score | 1.1 Scores on a scale | Standard Deviation 7.1 |
| Semaglutide 2.4 mg | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 social functioning score | 0.1 Scores on a scale | Standard Deviation 6.2 |
| Semaglutide 2.4 mg | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 mental health score | 0.2 Scores on a scale | Standard Deviation 6.2 |
| Semaglutide 2.4 mg | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 physical component summary | 0.8 Scores on a scale | Standard Deviation 4.9 |
| Semaglutide 2.4 mg | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 mental component summary | 0.0 Scores on a scale | Standard Deviation 6.2 |
| Semaglutide 2.4 mg | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 role-emotional score | 0.0 Scores on a scale | Standard Deviation 5.5 |
| Placebo | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 physical component summary | -0.9 Scores on a scale | Standard Deviation 5.6 |
| Placebo | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in physical functioning score (SF-36) | -1.2 Scores on a scale | Standard Deviation 4.5 |
| Placebo | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 social functioning score | -1.8 Scores on a scale | Standard Deviation 6.9 |
| Placebo | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 role-physical score | -0.9 Scores on a scale | Standard Deviation 5.3 |
| Placebo | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 role-emotional score | -2.2 Scores on a scale | Standard Deviation 7 |
| Placebo | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 bodily pain score | -1.5 Scores on a scale | Standard Deviation 7.7 |
| Placebo | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 mental health score | -2.2 Scores on a scale | Standard Deviation 7.6 |
| Placebo | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 general health score | -1.8 Scores on a scale | Standard Deviation 5.8 |
| Placebo | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 mental component summary | -2.4 Scores on a scale | Standard Deviation 8.5 |
| Placebo | Change in Physical Functioning Score (Short Form 36 [SF-36]) | Change in SF-36 vitality score | -2.1 Scores on a scale | Standard Deviation 7.6 |
Secondary
Change in Pulse
Change in pulse from week 20 and 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: Randomisation (week 20) to week 68
Population: SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Pulse | -2 bpm | Standard Deviation 9 |
| Placebo | Change in Pulse | -5 bpm | Standard Deviation 10 |
Secondary
Change in Pulse
Change in pulse rate from week 0 week to week 20 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: Run-in (week 0) to randomisation (week 20)
Population: SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Pulse | 5 beats per minute (bpm) | Standard Deviation 9 |
| Placebo | Change in Pulse | 5 beats per minute (bpm) | Standard Deviation 9 |
Secondary
Change in Systolic Blood Pressure
Change in systolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 | 0 Millimeters of mercury (mmHg) | Standard Deviation 14 |
| Placebo | Change in Systolic Blood Pressure | 5 Millimeters of mercury (mmHg) | Standard Deviation 13 |
Secondary
Change in Total Cholesterol
Change in fasting total cholesterol from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 | 1.05 Ratio of fasting total cholesterol | Geometric Coefficient of Variation 13.5 |
| Placebo | Change in Total Cholesterol | 1.11 Ratio of fasting total cholesterol | Geometric Coefficient of Variation 14.4 |
Secondary
Change in Triglycerides
Change in fasting triglycerides from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 | 0.94 Ratio of fasting triglycerides | Geometric Coefficient of Variation 33.9 |
| Placebo | Change in Triglycerides | 1.12 Ratio of fasting triglycerides | Geometric Coefficient of Variation 39.4 |
Secondary
Change in Very Low-density Lipoproteins (VLDL)
Change in fasting VLDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 Lipoproteins (VLDL) | 0.94 Ratio of fasting VLDL | Geometric Coefficient of Variation 33.6 |
| Placebo | Change in Very Low-density Lipoproteins (VLDL) | 1.12 Ratio of fasting VLDL | Geometric Coefficient of Variation 39 |
Secondary
Change in Waist Circumference
Change in waist circumference from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomization (week 20) 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 | -6.9 Centimeter (cm) | Standard Deviation 7.5 |
| Placebo | Change in Waist Circumference | 3.2 Centimeter (cm) | Standard Deviation 7 |
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 during run-in period from week 0 to week 20 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: Run-in (week 0) to randomisation (week 20)
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) | 23 Events |
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 during run-in period from week 0 to week 20 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: Randomisation (week 20) to week 75
Population: SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 2.4 mg | Number of Serious Adverse Events (SAEs) | 51 Events |
| Placebo | Number of Serious Adverse Events (SAEs) | 19 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 (week 0-20 run-in period). 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: Run-in (week 0) to randomisation (week 20)
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) | 3775 Events |
Secondary
Number of Treatment-emergent AEs
An 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 TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment (week 20-75). 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: Randomisation (week 20) to week 75
Population: SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 2.4 mg | Number of Treatment-emergent AEs | 1885 Events |
| Placebo | Number of Treatment-emergent AEs | 779 Events |
Secondary
Subjects Who Achieve (Yes/no): Body Weight Reduction < 0%
The number of participants who achieved less than (\<) 0% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved \<0% weight loss whereas 'No' infers number of participants who have not achieved \<0% 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Run-in (week 0) to week 68
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 | Subjects Who Achieve (Yes/no): Body Weight Reduction < 0% | Yes | 22 Participants |
| Semaglutide 2.4 mg | Subjects Who Achieve (Yes/no): Body Weight Reduction < 0% | No | 498 Participants |
| Placebo | Subjects Who Achieve (Yes/no): Body Weight Reduction < 0% | Yes | 51 Participants |
| Placebo | Subjects Who Achieve (Yes/no): Body Weight Reduction < 0% | No | 199 Participants |
Secondary
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10%
The number of participants who achieved ≥ 10% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Run-in (week 0) to week 68
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 | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10% | No | 109 Participants |
| Semaglutide 2.4 mg | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10% | Yes | 411 Participants |
| Placebo | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10% | No | 199 Participants |
| Placebo | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10% | Yes | 51 Participants |
Secondary
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15%
The number of participants who achieved ≥ 15% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Run-in (week 0) to week 68
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 | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15% | Yes | 331 Participants |
| Semaglutide 2.4 mg | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15% | No | 189 Participants |
| Placebo | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15% | Yes | 23 Participants |
| Placebo | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15% | No | 227 Participants |
Secondary
Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5%
The number of participants who achieved greater than or equal to (≥) 5% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 5% weight loss whereas 'No' infers number of participants who have not achieved ≥ 5% 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Run-in (week 0) to week 68
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 | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5% | Yes | 461 Participants |
| Semaglutide 2.4 mg | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5% | No | 59 Participants |
| Placebo | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5% | Yes | 119 Participants |
| Placebo | Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5% | No | 131 Participants |
Secondary
Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score
The number of participants achieving at least a 4.3-point increase in SF-36 physical functioning score from baseline (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved 4.3 points of increase of the score and 'No' infers number of participants who have not achieved 4.3 points of increase of the score. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomisation (week 20) to week 68
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 | Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Yes | 58 Participants |
| Semaglutide 2.4 mg | Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No | 457 Participants |
| Placebo | Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Yes | 11 Participants |
| Placebo | Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No | 234 Participants |
Secondary
Subjects Who Gain Weight (Yes/no)
The number of participants with weight gain from the start of the randomised period (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have gained weight and 'No' infers number of participants who have not gained weight. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).
Time frame: Randomisation (week 20) to week 68
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 | Subjects Who Gain Weight (Yes/no) | Yes | 79 Participants |
| Semaglutide 2.4 mg | Subjects Who Gain Weight (Yes/no) | No | 441 Participants |
| Placebo | Subjects Who Gain Weight (Yes/no) | Yes | 206 Participants |
| Placebo | Subjects Who Gain Weight (Yes/no) | No | 44 Participants |