Obesity, Overweight
Conditions
Brief summary
This study will look at the change in the 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 study medicine, the participant will have talks with study staff about healthy food choices, how to be more physically active and what else the participant can do to lose weight. Overweight and obesity is associated with an increased risk of type 2 diabetes. Therefore, weight loss has shown to have a beneficial impact on the blood sugar levels. The participant will either get semaglutide or dummy medicine - which treatment the participant get is decided by chance. The participant will need to take 2 injections at the same time 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
Subcutaneous (s.c.) injections of semaglutide once weekly at an escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week). The dose will be escalated to next level every 4 weeks.
Subcutaneous injections of semaglutide once weekly at an escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week, 1.7 mg/week and 2.4 mg/week). The dose will be escalated to next level every 4 weeks.
DRUGPlacebo I (Semaglutide)
S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide 2.4 mg (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week, 1.7 mg/week and 2.4 mg/week). The dose will be escalated to next level every 4 weeks.
DRUGPlacebo II (Semaglutide)
S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide 1.0 mg (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg 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 greater than or equal to 18 years at the time of signing informed consent * Body Mass Index (BMI) greater than or equal to 27 kg/m\^2 ' * History of at least one self-reported unsuccessful dietary effort to lose body weight * Diagnosed with type 2 diabetes (haemoglobin A1c 7-10% (53-86 mmol/mol) (both inclusive)) 180 days or longer prior to the day of screening
Exclusion criteria
* A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records * Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of less than 30 mL/min/1.73 m\^2 (less than 60 ml/min/1.73 m\^2 in subjects treated with Sodium-glucose Cotransporter 2 Inhibitors) according to chronic kidney disease (CKD)-Epidemiology Collaboration (EPI) creatinine equation as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 by the central laboratory at screening * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (e.g. optometrist) within the past 90 days prior to screening or in the period between screening and randomisation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight (%) - Semaglutide 2.4 mg Versus Placebo | Baseline (week 0) to week 68 | Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from both in-trial and on-treatment observation 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: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2-week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. |
| Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo | At week 68 | Number of participants who achieved weight reduction ≥5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Waist Circumference | Baseline (week 0) to week 68 | Change in waist circumference from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in Body Weight (Kg) | Baseline (week 0) to week 68 | Change in body weight (kg) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in BMI | Baseline (week 0) to week 68 | Change in body mass index (BMI) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% | At week 68 | Number of participants who achieved weight reduction ≥10% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% | At week 68 | Number of participants who achieved weight reduction ≥15% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Participants Who Achieve (Yes/no): Body Weight Reduction ≥20% | At week 68 | Number of participants who achieved weight reduction ≥20% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in HbA1c (%) | Baseline (week 0) to week 68 | Change in glycated haemoglobin (HbA1c (%)) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in Free Fatty Acids | Baseline (week 0) to week 68 | Change in free fatty acids (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in HbA1c (mmol/Mol) | Baseline (week 0) to week 68 | Change in HbA1c (mmol/mol) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in FPG (mg/dL) | Baseline (week 0) to week 68 | Change in fasting plasma glucose (FPG) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in Fasting Serum Insulin | Baseline (week 0) to week 68 | Change in fasting serum insulin from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol) | At week 68 | Number of participants who achieved HbA1c \<7% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Participants Who Achieve (Yes/no): HbA1c ≤6.5% (48 mmol/Mol) | At week 68 | Number of participants who achieved HbA1c ≤6.5% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% and HbA1c <7.0% | At week 68 | Number of participants who achieved weight reduction ≥10% of their baseline body weight and HbA1c \<7.0% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% and HbA1c <7.0% | At week 68 | Number of participants who achieved weight reduction ≥15% of their baseline body weight and HbA1c \<7.0% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| 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. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| 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. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in Total Cholesterol | Baseline (week 0) to week 68 | Change in total cholesterol (measured in milligram per decilitre (mg/dL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in HDL Cholesterol | Baseline (week 0) to week 68 | Change in high density lipoprotein (HDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in LDL Cholesterol | Baseline (week 0) to week 68 | Change in low density lipoprotein (LDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in VLDL Cholesterol | Baseline (week 0) to week 68 | Change in very low density lipoprotein (VLDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in Triglycerides | Baseline (week 0) to week 68 | Change in triglycerides (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in hsCRP | Baseline (week 0) to week 68 | Change in high sensitivity C-reactive protein (hsCRP; measured in milligram per ilitre (mg/L)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in PAI-1 Activity | Baseline (week 0) to week 68 | Change in Plasminogen Activator Inhibitor-1 (PAI-1; measured in arbritary units per millilitre (AU/mL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in Short Form 36 v2.0 Acute (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 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for 'physical functioning domain'. 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 were evaluated at week 68. A positive change score indicates an improvement since baseline. Results are based on the data from in-trial observation period. |
| Change in SF-36 (All Scores Except Physical Functioning) | 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 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for all the domains, except physical functioning. 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. Results are based on the data from in-trial observation period. |
| Change in IWQOL-Lite for CT (Physical Function Domain (5-items) Score) | Baseline (week 0) to week 68 | The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for 'physical function domain'. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in IWQOL-Lite for CT (All Scores Except Physical Function) | Baseline (week 0) to week 68 | The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for 'physical and psychosocial domains, and for total'. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | At week 68 | 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 the 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. Endpoint was evaluated based on in-trial observation period which is the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75). |
| Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | At week 68 | The observed number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 68 weeks was determined based on two different thresholds. The threshold of 20 was a preliminary responder threshold based on earlier studies. The threshold of 14.6 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on FDA recommendations. In the reported data, Yes infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and No infers the 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 was defined as the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75). |
| Number of TEAEs - Semaglutide 2.4 mg Versus Placebo | Week 0 to week 75 | Adverse events (AEs) with onset during the on-treatment observation period were defined as treatment-emergent AEs (TEAEs). On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least seven consecutive missed doses. |
| Number of SAEs - Semaglutide 2.4 mg Versus Placebo | Week 0 to week 75 | Serious adverse event (SAE) results are based on the on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least seven consecutive missed doses. |
| Number of Treatment Emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemia Episodes - Semaglutide 2.4 mg Versus Placebo | Week 0 to week 75 | Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least 7 consecutive missed doses. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following the return of PG to normal is considered sufficient evidence that the event was induced by a low PG concentration. Blood glucose (BG) confirmed symptomatic hypoglycaemia: An episode that is BG confirmed by PG value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. |
| Change in Body Weight (%) - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg | Baseline (week 0) to week 68 | Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
| Change in Amylase - Semaglutide 2.4 mg Versus Placebo | Baseline (week 0) to week 68 | Change in amylase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. |
| Change in Lipase - Semaglutide 2.4 mg Versus Placebo | Baseline (week 0) to week 68 | Change in lipase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. |
| Change in Calcitonin - Semaglutide 2.4 mg Versus Placebo | Baseline (week 0) to week 68 | Change in calcitonin (nanogram/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. |
| Change in Pulse - Semaglutide 2.4 mg Versus Placebo | Baseline (week 0) to week 68 | Change in pulse from baseline (week 0) to week 68 is presented. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. |
| Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg | At week 68 | Number of participants who achieved weight reduction ≥5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. |
Countries
Argentina, Canada, Germany, Greece, India, Japan, Puerto Rico, Russia, South Africa, Spain, United Arab Emirates, United Kingdom, United States
Participant flow
Recruitment details
The trial was conducted at 149 sites in 12 countries as follows: Argentina (5 sites), Canada (10 sites), Germany (9 sites), Greece (6 sites), India (18 sites), Japan (12 sites), Russian Federation (9 sites), South Africa (6 sites), Spain (8 sites), United Arab Emirates (5 sites), United Kingdom (10 sites) and United States (51 sites).
Pre-assignment details
Participants were randomised in 1:1:1 ratio to receive either 'semaglutide 2.4 milligram (mg) and placebo II (placebo matched to semaglutide 1.0 mg) once weekly', 'semaglutide 1.0 mg and placebo I (placebo matched to semaglutide 2.4 mg) once weekly' or 'placebo I and placebo II once weekly'.
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide 1.0 mg Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity. | 403 |
| Semaglutide 2.4 mg Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity. | 404 |
| Placebo Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity. | 403 |
| Total | 1,210 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 7 | 7 |
| Overall Study | Withdrawal by Subject | 10 | 5 | 12 |
Baseline characteristics
| Characteristic | Semaglutide 1.0 mg | Semaglutide 2.4 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 56 Year STANDARD_DEVIATION 10 | 55 Year STANDARD_DEVIATION 11 | 55 Year STANDARD_DEVIATION 11 | 55 Year STANDARD_DEVIATION 11 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Asian | 97 Participants | 112 Participants | 108 Participants | 317 Participants |
| Race/Ethnicity, Customized Black or African American | 28 Participants | 35 Participants | 37 Participants | 100 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 59 Participants | 47 Participants | 49 Participants | 155 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Applicable | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 344 Participants | 357 Participants | 354 Participants | 1055 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 16 Participants | 13 Participants | 35 Participants |
| Race/Ethnicity, Customized White | 272 Participants | 237 Participants | 242 Participants | 751 Participants |
| Sex: Female, Male Female | 203 Participants | 223 Participants | 190 Participants | 616 Participants |
| Sex: Female, Male Male | 200 Participants | 181 Participants | 213 Participants | 594 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 402 | 1 / 403 | 1 / 402 |
| other Total, other adverse events | 261 / 402 | 284 / 403 | 190 / 402 |
| serious Total, serious adverse events | 31 / 402 | 40 / 403 | 37 / 402 |
Outcome results
Primary
Change in Body Weight (%) - Semaglutide 2.4 mg Versus Placebo
Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from both in-trial and on-treatment observation 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: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2-week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time frame: Baseline (week 0) to week 68
Population: Overall number of participants analysed = FAS which comprised all randomised participants. Number analysed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 2.4 mg | Change in Body Weight (%) - Semaglutide 2.4 mg Versus Placebo | In-trial observation period | -9.9 Percentage point of body weight | Standard Deviation 8 |
| Semaglutide 2.4 mg | Change in Body Weight (%) - Semaglutide 2.4 mg Versus Placebo | On-treatment observation period | -10.7 Percentage point of body weight | Standard Deviation 7.8 |
| Placebo | Change in Body Weight (%) - Semaglutide 2.4 mg Versus Placebo | In-trial observation period | -3.3 Percentage point of body weight | Standard Deviation 5.5 |
| Placebo | Change in Body Weight (%) - Semaglutide 2.4 mg Versus Placebo | On-treatment observation period | -3.1 Percentage point of body weight | Standard Deviation 5.2 |
Comparison: Results are based on the data from in-trial observation period. Week 68 responses were analysed using an analysis of covariance model (ANCOVA) with randomised treatment, stratification groups (oral anti-diabetic (OAD) treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate.p-value: <0.000195% CI: [-7.28, -5.15]ANCOVA
Comparison: Results are based on the data from on-treatment observation period. All responses prior to first discontinuation of treatment (or initiation of other anti-obesity medication or bariatric surgery) were included in a mixed model for repeated measurements (MMRM) with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate, all nested within visit.p-value: <0.000195% CI: [-8.56, -6.58]MMRM
Primary
Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo
Number of participants who achieved weight reduction ≥5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time frame: At week 68
Population: Overall number of participants analysed = FAS which comprised all randomised participants. Number analysed = 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 ≥5% - Semaglutide 2.4 mg Versus Placebo | On-treatment observation period | No | 94 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo | In-trial observation period | Yes | 267 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo | In-trial observation period | No | 121 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo | On-treatment observation period | Yes | 257 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo | On-treatment observation period | Yes | 94 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo | On-treatment observation period | No | 246 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo | In-trial observation period | No | 269 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo | In-trial observation period | Yes | 107 Participants |
Comparison: Results are based on the data from in-trial observation period. Week 68 responses were analysed using a binary logistic regression model with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate.p-value: <0.000195% CI: [3.58, 6.64]Regression, Logistic
Comparison: Results are based on the data from on-treatment observation period. All responses prior to first discontinuation of treatment (or initiation of other anti-obesity medication or bariatric surgery) were included in a MMRM with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate, all nested within visit.p-value: <0.000195% CI: [6.31, 11.97]Regression, Logistic
Secondary
Change in Amylase - Semaglutide 2.4 mg Versus Placebo
Change in amylase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time frame: Baseline (week 0) to week 68
Population: SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Amylase - Semaglutide 2.4 mg Versus Placebo | 1.24 Ratio of amylase | Geometric Coefficient of Variation 28.3 |
| Placebo | Change in Amylase - Semaglutide 2.4 mg Versus Placebo | 1.06 Ratio of amylase | Geometric Coefficient of Variation 25 |
Secondary
Change in BMI
Change in body mass index (BMI) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in BMI | -2.6 kilogram per square meter (kg/m^2) | Standard Deviation 2.4 |
| Placebo | Change in BMI | -3.6 kilogram per square meter (kg/m^2) | Standard Deviation 3.1 |
| Placebo | Change in BMI | -1.2 kilogram per square meter (kg/m^2) | Standard Deviation 2.1 |
Secondary
Change in Body Weight (Kg)
Change in body weight (kg) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Body Weight (Kg) | -7.1 Kilogram (kg) | Standard Deviation 6.7 |
| Placebo | Change in Body Weight (Kg) | -9.9 Kilogram (kg) | Standard Deviation 8.5 |
| Placebo | Change in Body Weight (Kg) | -3.4 Kilogram (kg) | Standard Deviation 6.2 |
Secondary
Change in Body Weight (%) - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg
Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Body Weight (%) - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg | -9.9 Percentage point of body weight | Standard Deviation 8 |
| Placebo | Change in Body Weight (%) - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg | -7.2 Percentage point of body weight | Standard Deviation 6.6 |
Secondary
Change in Calcitonin - Semaglutide 2.4 mg Versus Placebo
Change in calcitonin (nanogram/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time frame: Baseline (week 0) to week 68
Population: SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Calcitonin - Semaglutide 2.4 mg Versus Placebo | 0.94 Ratio of calcitonin | Geometric Coefficient of Variation 60.3 |
| Placebo | Change in Calcitonin - Semaglutide 2.4 mg Versus Placebo | 0.96 Ratio of calcitonin | Geometric Coefficient of Variation 38.6 |
Secondary
Change in Diastolic Blood Pressure
Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Diastolic Blood Pressure | -1 Millimetre of mercury (mmHg) | Standard Deviation 9 |
| Placebo | Change in Diastolic Blood Pressure | -2 Millimetre of mercury (mmHg) | Standard Deviation 9 |
| Placebo | Change in Diastolic Blood Pressure | -1 Millimetre of mercury (mmHg) | Standard Deviation 9 |
Secondary
Change in Fasting Serum Insulin
Change in fasting serum insulin from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Fasting Serum Insulin | 0.94 Picomoles per litre (pmol/L) | Geometric Coefficient of Variation 59.8 |
| Placebo | Change in Fasting Serum Insulin | 0.90 Picomoles per litre (pmol/L) | Geometric Coefficient of Variation 65.4 |
| Placebo | Change in Fasting Serum Insulin | 0.93 Picomoles per litre (pmol/L) | Geometric Coefficient of Variation 53.6 |
Secondary
Change in FPG (mg/dL)
Change in fasting plasma glucose (FPG) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in FPG (mg/dL) | -36.5 milligrams per deciliter (mg/dL) | Standard Deviation 45.1 |
| Placebo | Change in FPG (mg/dL) | -37.9 milligrams per deciliter (mg/dL) | Standard Deviation 45.9 |
| Placebo | Change in FPG (mg/dL) | -2.3 milligrams per deciliter (mg/dL) | Standard Deviation 53.1 |
Secondary
Change in Free Fatty Acids
Change in free fatty acids (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Free Fatty Acids | 0.85 Ratio of free fatty acids | Geometric Coefficient of Variation 61.4 |
| Placebo | Change in Free Fatty Acids | 0.84 Ratio of free fatty acids | Geometric Coefficient of Variation 68.7 |
| Placebo | Change in Free Fatty Acids | 1.01 Ratio of free fatty acids | Geometric Coefficient of Variation 62.3 |
Secondary
Change in HbA1c (%)
Change in glycated haemoglobin (HbA1c (%)) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in HbA1c (%) | -1.5 Percentage point of HbA1c | Standard Deviation 1.1 |
| Placebo | Change in HbA1c (%) | -1.7 Percentage point of HbA1c | Standard Deviation 1.2 |
| Placebo | Change in HbA1c (%) | -0.3 Percentage point of HbA1c | Standard Deviation 1.3 |
Secondary
Change in HbA1c (mmol/Mol)
Change in HbA1c (mmol/mol) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in HbA1c (mmol/Mol) | -16.9 millimoles per mole (mmol/mol) | Standard Deviation 12.3 |
| Placebo | Change in HbA1c (mmol/Mol) | -18.7 millimoles per mole (mmol/mol) | Standard Deviation 13 |
| Placebo | Change in HbA1c (mmol/Mol) | -3.4 millimoles per mole (mmol/mol) | Standard Deviation 14.3 |
Secondary
Change in HDL Cholesterol
Change in high density lipoprotein (HDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in HDL Cholesterol | 1.06 Ratio of HDL cholesterol | Geometric Coefficient of Variation 16 |
| Placebo | Change in HDL Cholesterol | 1.07 Ratio of HDL cholesterol | Geometric Coefficient of Variation 15.7 |
| Placebo | Change in HDL Cholesterol | 1.04 Ratio of HDL cholesterol | Geometric Coefficient of Variation 15.3 |
Secondary
Change in hsCRP
Change in high sensitivity C-reactive protein (hsCRP; measured in milligram per ilitre (mg/L)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in hsCRP | 0.59 Ratio of hsCRP | Geometric Coefficient of Variation 115.7 |
| Placebo | Change in hsCRP | 0.50 Ratio of hsCRP | Geometric Coefficient of Variation 125.7 |
| Placebo | Change in hsCRP | 0.84 Ratio of hsCRP | Geometric Coefficient of Variation 90.9 |
Secondary
Change in IWQOL-Lite for CT (All Scores Except Physical Function)
The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for 'physical and psychosocial domains, and for total'. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 2.4 mg | Change in IWQOL-Lite for CT (All Scores Except Physical Function) | Psychosocial | 8.6 Score on a scale | Standard Deviation 15.7 |
| Semaglutide 2.4 mg | Change in IWQOL-Lite for CT (All Scores Except Physical Function) | Total | 8.2 Score on a scale | Standard Deviation 14.8 |
| Semaglutide 2.4 mg | Change in IWQOL-Lite for CT (All Scores Except Physical Function) | Physical | 7.6 Score on a scale | Standard Deviation 18 |
| Placebo | Change in IWQOL-Lite for CT (All Scores Except Physical Function) | Physical | 11.0 Score on a scale | Standard Deviation 19.6 |
| Placebo | Change in IWQOL-Lite for CT (All Scores Except Physical Function) | Psychosocial | 9.6 Score on a scale | Standard Deviation 16.7 |
| Placebo | Change in IWQOL-Lite for CT (All Scores Except Physical Function) | Total | 10.1 Score on a scale | Standard Deviation 15.9 |
| Placebo | Change in IWQOL-Lite for CT (All Scores Except Physical Function) | Total | 5.2 Score on a scale | Standard Deviation 15.5 |
| Placebo | Change in IWQOL-Lite for CT (All Scores Except Physical Function) | Psychosocial | 5.6 Score on a scale | Standard Deviation 16.5 |
| Placebo | Change in IWQOL-Lite for CT (All Scores Except Physical Function) | Physical | 4.4 Score on a scale | Standard Deviation 19.1 |
Secondary
Change in IWQOL-Lite for CT (Physical Function Domain (5-items) Score)
The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for 'physical function domain'. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in IWQOL-Lite for CT (Physical Function Domain (5-items) Score) | 8.5 Score on a scale | Standard Deviation 18.8 |
| Placebo | Change in IWQOL-Lite for CT (Physical Function Domain (5-items) Score) | 11.4 Score on a scale | Standard Deviation 20.8 |
| Placebo | Change in IWQOL-Lite for CT (Physical Function Domain (5-items) Score) | 4.9 Score on a scale | Standard Deviation 20.4 |
Secondary
Change in LDL Cholesterol
Change in low density lipoprotein (LDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in LDL Cholesterol | 0.99 Ratio of LDL cholesterol | Geometric Coefficient of Variation 37.5 |
| Placebo | Change in LDL Cholesterol | 1.00 Ratio of LDL cholesterol | Geometric Coefficient of Variation 30.9 |
| Placebo | Change in LDL Cholesterol | 1.00 Ratio of LDL cholesterol | Geometric Coefficient of Variation 28.9 |
Secondary
Change in Lipase - Semaglutide 2.4 mg Versus Placebo
Change in lipase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time frame: Baseline (week 0) to week 68
Population: SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Lipase - Semaglutide 2.4 mg Versus Placebo | 1.41 Ratio of lipase | Geometric Coefficient of Variation 57.2 |
| Placebo | Change in Lipase - Semaglutide 2.4 mg Versus Placebo | 0.99 Ratio of lipase | Geometric Coefficient of Variation 51.8 |
Secondary
Change in PAI-1 Activity
Change in Plasminogen Activator Inhibitor-1 (PAI-1; measured in arbritary units per millilitre (AU/mL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in PAI-1 Activity | 1.21 Ratio of PAI-1 activity | Geometric Coefficient of Variation 73.7 |
| Placebo | Change in PAI-1 Activity | 1.06 Ratio of PAI-1 activity | Geometric Coefficient of Variation 80.8 |
| Placebo | Change in PAI-1 Activity | 1.42 Ratio of PAI-1 activity | Geometric Coefficient of Variation 68.9 |
Secondary
Change in Pulse - Semaglutide 2.4 mg Versus Placebo
Change in pulse from baseline (week 0) to week 68 is presented. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time frame: Baseline (week 0) to week 68
Population: SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Pulse - Semaglutide 2.4 mg Versus Placebo | 2 Beats/minute | Standard Deviation 9 |
| Placebo | Change in Pulse - Semaglutide 2.4 mg Versus Placebo | 0 Beats/minute | Standard Deviation 9 |
Secondary
Change in SF-36 (All Scores Except Physical Functioning)
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 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for all the domains, except physical functioning. 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. Results are based on the data from in-trial observation period.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Semaglutide 2.4 mg | Change in SF-36 (All Scores Except Physical Functioning) | Vitality | -0.1 Score on a scale | Standard Deviation 7.8 |
| Semaglutide 2.4 mg | Change in SF-36 (All Scores Except Physical Functioning) | Bodily Pain | 0.4 Score on a scale | Standard Deviation 8.3 |
| Semaglutide 2.4 mg | Change in SF-36 (All Scores Except Physical Functioning) | Role-Emotional | -0.4 Score on a scale | Standard Deviation 7.3 |
| Semaglutide 2.4 mg | Change in SF-36 (All Scores Except Physical Functioning) | Role-Physical | 0.6 Score on a scale | Standard Deviation 6.9 |
| Semaglutide 2.4 mg | Change in SF-36 (All Scores Except Physical Functioning) | Physical component summary | 1.9 Score on a scale | Standard Deviation 6.4 |
| Semaglutide 2.4 mg | Change in SF-36 (All Scores Except Physical Functioning) | Mental Health | -0.9 Score on a scale | Standard Deviation 7.5 |
| Semaglutide 2.4 mg | Change in SF-36 (All Scores Except Physical Functioning) | General Health | 1.7 Score on a scale | Standard Deviation 7.2 |
| Semaglutide 2.4 mg | Change in SF-36 (All Scores Except Physical Functioning) | Mental component summary | -1.4 Score on a scale | Standard Deviation 7.4 |
| Semaglutide 2.4 mg | Change in SF-36 (All Scores Except Physical Functioning) | Social Functioning | -0.3 Score on a scale | Standard Deviation 6.6 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Vitality | 0.8 Score on a scale | Standard Deviation 7.9 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Mental Health | -0.4 Score on a scale | Standard Deviation 6.9 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | General Health | 2.2 Score on a scale | Standard Deviation 7.3 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Physical component summary | 2.3 Score on a scale | Standard Deviation 7.2 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Mental component summary | -0.9 Score on a scale | Standard Deviation 6.9 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Bodily Pain | 0.3 Score on a scale | Standard Deviation 9 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Role-Physical | 0.8 Score on a scale | Standard Deviation 7.4 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Role-Emotional | -0.4 Score on a scale | Standard Deviation 7.7 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Social Functioning | 0.2 Score on a scale | Standard Deviation 6.6 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Mental component summary | -1.8 Score on a scale | Standard Deviation 7.6 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Vitality | -0.9 Score on a scale | Standard Deviation 7.9 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Social Functioning | -0.7 Score on a scale | Standard Deviation 7.4 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Role-Emotional | -1.1 Score on a scale | Standard Deviation 7.8 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Physical component summary | 0.9 Score on a scale | Standard Deviation 6.6 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Bodily Pain | -0.4 Score on a scale | Standard Deviation 8.6 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | General Health | 0.6 Score on a scale | Standard Deviation 7.5 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Mental Health | -1.6 Score on a scale | Standard Deviation 7.5 |
| Placebo | Change in SF-36 (All Scores Except Physical Functioning) | Role-Physical | 0.0 Score on a scale | Standard Deviation 7.1 |
Secondary
Change in Short Form 36 v2.0 Acute (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 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for 'physical functioning domain'. 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 were evaluated at week 68. A positive change score indicates an improvement since baseline. Results are based on the data from in-trial observation period.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Short Form 36 v2.0 Acute (SF-36) (Physical Functioning Score) | 2.1 Score on a scale | Standard Deviation 6.8 |
| Placebo | Change in Short Form 36 v2.0 Acute (SF-36) (Physical Functioning Score) | 2.8 Score on a scale | Standard Deviation 7.7 |
| Placebo | Change in Short Form 36 v2.0 Acute (SF-36) (Physical Functioning Score) | 0.8 Score on a scale | Standard Deviation 7 |
Secondary
Change in Systolic Blood Pressure
Change in systolic blood pressure from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Systolic Blood Pressure | -3 Millimetre of mercury (mmHg) | Standard Deviation 15 |
| Placebo | Change in Systolic Blood Pressure | -4 Millimetre of mercury (mmHg) | Standard Deviation 14 |
| Placebo | Change in Systolic Blood Pressure | 0 Millimetre of mercury (mmHg) | Standard Deviation 15 |
Secondary
Change in Total Cholesterol
Change in total cholesterol (measured in milligram per decilitre (mg/dL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Total Cholesterol | 0.97 Ratio of total cholesterol | Geometric Coefficient of Variation 20.1 |
| Placebo | Change in Total Cholesterol | 0.99 Ratio of total cholesterol | Geometric Coefficient of Variation 17.9 |
| Placebo | Change in Total Cholesterol | 1.00 Ratio of total cholesterol | Geometric Coefficient of Variation 18.9 |
Secondary
Change in Triglycerides
Change in triglycerides (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Triglycerides | 0.81 Ratio of triglycerides | Geometric Coefficient of Variation 44.5 |
| Placebo | Change in Triglycerides | 0.79 Ratio of triglycerides | Geometric Coefficient of Variation 43.8 |
| Placebo | Change in Triglycerides | 0.92 Ratio of triglycerides | Geometric Coefficient of Variation 44.5 |
Secondary
Change in VLDL Cholesterol
Change in very low density lipoprotein (VLDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in VLDL Cholesterol | 0.82 Ratio of VLDL cholesterol | Geometric Coefficient of Variation 42.1 |
| Placebo | Change in VLDL Cholesterol | 0.80 Ratio of VLDL cholesterol | Geometric Coefficient of Variation 42 |
| Placebo | Change in VLDL Cholesterol | 0.92 Ratio of VLDL cholesterol | Geometric Coefficient of Variation 40.5 |
Secondary
Change in Waist Circumference
Change in waist circumference from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: Baseline (week 0) to week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide 2.4 mg | Change in Waist Circumference | -6.9 Centimetre (cm) | Standard Deviation 6.8 |
| Placebo | Change in Waist Circumference | -9.7 Centimetre (cm) | Standard Deviation 8.1 |
| Placebo | Change in Waist Circumference | -4.3 Centimetre (cm) | Standard Deviation 6.5 |
Secondary
Number of SAEs - Semaglutide 2.4 mg Versus Placebo
Serious adverse event (SAE) results are based on the on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least seven consecutive missed doses.
Time frame: Week 0 to week 75
Population: SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 2.4 mg | Number of SAEs - Semaglutide 2.4 mg Versus Placebo | 71 Events |
| Placebo | Number of SAEs - Semaglutide 2.4 mg Versus Placebo | 53 Events |
Secondary
Number of TEAEs - Semaglutide 2.4 mg Versus Placebo
Adverse events (AEs) with onset during the on-treatment observation period were defined as treatment-emergent AEs (TEAEs). On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least seven consecutive missed doses.
Time frame: Week 0 to week 75
Population: Safety analysis set (SAS) included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 2.4 mg | Number of TEAEs - Semaglutide 2.4 mg Versus Placebo | 2197 Events |
| Placebo | Number of TEAEs - Semaglutide 2.4 mg Versus Placebo | 1388 Events |
Secondary
Number of Treatment Emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemia Episodes - Semaglutide 2.4 mg Versus Placebo
Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least 7 consecutive missed doses. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following the return of PG to normal is considered sufficient evidence that the event was induced by a low PG concentration. Blood glucose (BG) confirmed symptomatic hypoglycaemia: An episode that is BG confirmed by PG value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time frame: Week 0 to week 75
Population: SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Semaglutide 2.4 mg | Number of Treatment Emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemia Episodes - Semaglutide 2.4 mg Versus Placebo | 51 Episodes |
| Placebo | Number of Treatment Emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemia Episodes - Semaglutide 2.4 mg Versus Placebo | 18 Episodes |
Secondary
Participants Who Achieve (Yes/no): Body Weight Reduction ≥10%
Number of participants who achieved weight reduction ≥10% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: At week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% | Yes | 109 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% | No | 271 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% | No | 211 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% | Yes | 177 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% | No | 345 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% | Yes | 31 Participants |
Secondary
Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% and HbA1c <7.0%
Number of participants who achieved weight reduction ≥10% of their baseline body weight and HbA1c \<7.0% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: At week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% and HbA1c <7.0% | No | 271 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% and HbA1c <7.0% | Yes | 105 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% and HbA1c <7.0% | Yes | 170 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% and HbA1c <7.0% | No | 211 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% and HbA1c <7.0% | Yes | 25 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% and HbA1c <7.0% | No | 349 Participants |
Secondary
Participants Who Achieve (Yes/no): Body Weight Reduction ≥15%
Number of participants who achieved weight reduction ≥15% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: At week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% | Yes | 52 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% | No | 328 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% | No | 288 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% | Yes | 100 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% | No | 364 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% | Yes | 12 Participants |
Secondary
Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% and HbA1c <7.0%
Number of participants who achieved weight reduction ≥15% of their baseline body weight and HbA1c \<7.0% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: At week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% and HbA1c <7.0% | No | 327 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% and HbA1c <7.0% | Yes | 49 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% and HbA1c <7.0% | No | 283 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% and HbA1c <7.0% | Yes | 98 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% and HbA1c <7.0% | Yes | 11 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% and HbA1c <7.0% | No | 363 Participants |
Secondary
Participants Who Achieve (Yes/no): Body Weight Reduction ≥20%
Number of participants who achieved weight reduction ≥20% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: At week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥20% | Yes | 18 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥20% | No | 362 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥20% | Yes | 51 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥20% | No | 337 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥20% | No | 370 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥20% | Yes | 6 Participants |
Secondary
Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg
Number of participants who achieved weight reduction ≥5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: At week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg | Yes | 267 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg | No | 121 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg | Yes | 217 Participants |
| Placebo | Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg | No | 163 Participants |
Secondary
Participants Who Achieve (Yes/no): HbA1c ≤6.5% (48 mmol/Mol)
Number of participants who achieved HbA1c ≤6.5% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: At week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): HbA1c ≤6.5% (48 mmol/Mol) | Yes | 226 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): HbA1c ≤6.5% (48 mmol/Mol) | No | 150 Participants |
| Placebo | Participants Who Achieve (Yes/no): HbA1c ≤6.5% (48 mmol/Mol) | Yes | 257 Participants |
| Placebo | Participants Who Achieve (Yes/no): HbA1c ≤6.5% (48 mmol/Mol) | No | 124 Participants |
| Placebo | Participants Who Achieve (Yes/no): HbA1c ≤6.5% (48 mmol/Mol) | Yes | 58 Participants |
| Placebo | Participants Who Achieve (Yes/no): HbA1c ≤6.5% (48 mmol/Mol) | No | 316 Participants |
Secondary
Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol)
Number of participants who achieved HbA1c \<7% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time frame: At week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol) | Yes | 272 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol) | No | 104 Participants |
| Placebo | Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol) | Yes | 299 Participants |
| Placebo | Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol) | No | 82 Participants |
| Placebo | Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol) | Yes | 99 Participants |
| Placebo | Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol) | No | 275 Participants |
Secondary
Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score
The observed number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 68 weeks was determined based on two different thresholds. The threshold of 20 was a preliminary responder threshold based on earlier studies. The threshold of 14.6 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on FDA recommendations. In the reported data, Yes infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and No infers the 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 was defined as the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).
Time frame: At week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | Yes (with threshold 20) | 107 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | No (with threshold 20) | 262 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | Yes (with threshold 14.6) | 144 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | No (with threshold 14.6) | 225 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | Yes (with threshold 14.6) | 160 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | No (with threshold 14.6) | 216 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | Yes (with threshold 20) | 131 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | No (with threshold 20) | 245 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | No (with threshold 14.6) | 252 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | Yes (with threshold 14.6) | 113 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | No (with threshold 20) | 282 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score | Yes (with threshold 20) | 83 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 the 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. Endpoint was evaluated based on in-trial observation period which is the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).
Time frame: At week 68
Population: FAS included all randomised participants. 'Overall Number of Participants Analysed' = 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 3.7) | 130 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No (with threshold 3.7) | 240 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No (with threshold 4.3) | 282 Participants |
| Semaglutide 2.4 mg | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Yes (with threshold 4.3) | 88 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No (with threshold 3.7) | 218 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Yes (with threshold 4.3) | 111 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Yes (with threshold 3.7) | 158 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No (with threshold 4.3) | 265 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Yes (with threshold 4.3) | 68 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No (with threshold 4.3) | 297 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | Yes (with threshold 3.7) | 102 Participants |
| Placebo | Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score | No (with threshold 3.7) | 263 Participants |