Obesity
Conditions
Brief summary
This study will look at how much weight participants will lose from the start to the end of the study. The weight loss in participants taking the investigational high dose of semaglutide will be compared to the weight loss in people taking "dummy" medicine and a lower dose of semaglutide. In addition to taking the medicine, participants will have talks with study staff about healthy food choices and how to be more physically active. Participants will either get semaglutide or "dummy" medicine. Which treatment participants get is decided by chance. Participants are more likely (4 out of 5) to get semaglutide than the "dummy" medicine. The study medicine will be injected briefly, under skin, with a thin needle, typically in the stomach, thighs, or upper arms. In the first part of the study, participants will get one injection once a week until they reach the planned dose. The second part of the study, which might last a couple of months, is a transition period, where participant will get three injections, taken right after each other, once a week. The duration of the study intervention (trial product and lifestyle intervention) will be 72 weeks followed by a 9-week follow-up period without study interventions.
Interventions
DRUGSemaglutide
Participants will receive once-weekly s.c. injections of semaglutide in escalating doses (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, 2.4 mg and 7.2 mg) every fourth week. Treatment was continued on the maintenance dose of 7.2 mg once-weekly for an additional 52 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.
DRUGPlacebo
Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.
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 above or equal to 18 years at the time of signing informed consent. * Body mass index (BMI) greater than or equal to 30.0 kilogram per square meter (kg/m\^2). * History of at least one self-reported unsuccessful dietary effort to lose body weight.
Exclusion criteria
* HbA1c greater than or equal to 48 millimoles per mole (mmol/mol) (6.5 percent) as measured by the central laboratory at screening. * History of type 1 or type 2 diabetes. * Treatment with glucose-lowering agent(s) within 90 days before screening. * A self-reported change in body weight greater than 5 kilograms (kg) (11 pounds) within 90 days before screening irrespective of medical records. * Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Semaglutide 7.2 mg Versus Placebo: Relative Change in Body Weight | Baseline (week 0), End of treatment (week 72) | Relative change in body weight from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction Greater Than or Equal to (>=) 5% (Yes/no) | At week 72 | Number of participants who achieve body weight reduction \>=5% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction \>=5% and "no" defines participants who did not achieve body weight reduction \>=5%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=10% (Yes/no) | At week 72 | Number of participants who achieve body weight reduction \>=10% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction \>=10% and "no" defines participants who did not achieve body weight reduction \>=10%. |
| Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=15% (Yes/no) | At week 72 | Number of participants who achieve body weight reduction \>=15% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction \>=15% and "no" defines participants who did not achieve body weight reduction \>=15%. |
| Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=20% (Yes/no) | At week 72 | Number of participants who achieve body weight reduction \>=20% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction \>=20% and "no" defines participants who did not achieve body weight reduction \>=20%. |
| Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=25% (Yes/no) | At week 72 | Number of participants who achieve body weight reduction \>=25% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction \>=25% and "no" defines participants who did not achieve body weight reduction \>=25%. |
| Semaglutide 7.2 mg Versus Placebo: Change in Waist Circumference | Baseline (week 0), End of treatment (week 72) | Change in waist circumference from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Relative Change in Body Weight | Baseline (week 0), End of treatment (week 72) | Relative change in body weight from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of Participants Who Achieve Body Weight Reduction >=20% (Yes/no) | At week 72 | Number of participants who achieve body weight reduction \>=20% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction \>=20% and "no" defines participants who did not achieve body weight reduction \>=20%. |
| Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of Participants Who Achieve Body Weight Reduction >=25% (Yes/no) | At week 72 | Number of participants who achieve body weight reduction \>=25% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction \>=25% and "no" defines participants who did not achieve body weight reduction \>=25%. |
| Semaglutide 7.2 mg Versus Placebo: Change in Body Weight | Baseline (week 0), End of treatment (week 72) | Change in body weight from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Placebo: Change in Body Mass Index (BMI) | Baseline (week 0), End of treatment (week 72) | Change in BMI from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Change in Body Weight | Baseline (week 0), End of treatment (week 72) | Change in body weight from baseline (week 0) to end of treatment (week 72) is presented. |
| Pooled Semaglutide Versus Placebo: Change in Total Fat Volume (%) | Baseline (week 0), End of treatment (week 72) | Change in total fat volume (%) from baseline (week 0) to end of treatment (week 72) is presented. |
| Pooled Semaglutide Versus Placebo: Change in Total Fat Volume (Liters) | Baseline (week 0), End of treatment (week 72) | Change in total fat volume (liters) from baseline (week 0) to end of treatment (week 72) is presented. |
| Pooled Semaglutide Versus Placebo: Change in Lean Body Volume (%) | Baseline (week 0), End of treatment (week 72) | Change in lean body volume (%) from baseline (week 0) to end of treatment (week 72) is presented. |
| Pooled Semaglutide Versus Placebo: Change in Lean Body Volume (Liters) | Baseline (week 0), End of treatment (week 72) | Change in lean body volume (liters) from baseline (week 0) to end of treatment (week 72) is presented. |
| Pooled Semaglutide Versus Placebo: Change in Visceral Fat Volume (%) | Baseline (week 0), End of treatment (week 72) | Change in visceral fat volume (%) from baseline (week 0) to end of treatment (week 72) is presented. |
| Pooled Semaglutide Versus Placebo: Change in Visceral Fat Volume (Liters) | Baseline (week 0), End of treatment (week 72) | Change in visceral fat volume (liters) from baseline (week 0) to end of treatment (week 72) is presented. |
| Pooled Semaglutide Versus Placebo: Change in Body Weight (%) | Baseline (week 0), End of treatment (week 72) | Change in body weight (%) from baseline (week 0) to end of treatment (week 72) is presented. |
| Pooled Semaglutide Versus Placebo: Change in Body Weight (Kg) | Baseline (week 0), End of treatment (week 72) | Change in body weight (Kg) from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Placebo: Change in Systolic Blood Pressure | Baseline (week 0), End of treatment (week 72) | Change in systolic blood pressure from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Placebo: Change in Diastolic Blood Pressure | Baseline (week 0), End of treatment (week 72) | Change in diastolic blood pressure from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Placebo: Change in Total Cholesterol (Milligram Per Deciliter [mg/dL]) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in total cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Change in Total Cholesterol (Millimoles Per Liter [mmol/L]) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in total cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Change in High-density Lipoprotein (HDL) Cholesterol (mg/dL) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in HDL cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Change in High-density Lipoprotein (HDL) Cholesterol (mmol/L) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in HDL cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Change in Low-density Lipoprotein (LDL) Cholesterol (mg/dL)- Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in LDL cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Change in Low-density Lipoprotein (LDL) Cholesterol (mmol/L)- Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in LDL cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Change in Very Low-density Lipoprotein (VLDL) Cholesterol (mg/dL) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in VLDL cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Change in Very Low-density Lipoprotein (VLDL) Cholesterol (mmol/L) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in VLDL cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Change in Triglycerides (mg/dL) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in triglycerides in mg/dL from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Change in Triglycerides (mmol/L) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in triglycerides in mmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Change in High-sensitivity C-reactive Protein (hsCRP) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in hsCRP (milligram per liter \[mg/L\]) from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Number of Participants With Change in Lipid-lowering Treatment (Decrease, no Change, Increase) | At week 72 | Number of participants with change in lipid-lowering treatment from baseline (week 0) is presented in categories as decrease, no change and increase. |
| Semaglutide 7.2 mg Versus Placebo: Number of Participants With Change in Antihypertensive Treatment (Decrease, no Change, Increase) | At week 72 | Number of participants with change in antihypertensive treatment from baseline (week 0) is presented in categories as decrease, no change and increase. |
| Semaglutide 7.2 mg Versus Placebo: Change in Glycated Haemoglobin (HbA1c) | Baseline (week 0), End of treatment (week 72) | Change in HbA1c from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Placebo: Change in Fasting Plasma Glucose | Baseline (week 0), End of treatment (week 72) | Change in fasting plasma glucose from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Placebo: Change in Fasting Serum Insulin (Picomoles Per Liter [Pmol/L]) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in fasting serum insulin in pmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Change in Fasting Serum Insulin (Milliinternational Units Per Milliliter [mIU/mL]) - Ratio to Baseline | Baseline (week 0), End of treatment (week 72) | Change in fasting serum insulin in mIU/ml from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0). |
| Semaglutide 7.2 mg Versus Placebo: Number of Participants With Change in Glycaemic Category (Normo-glycaemia, Pre-diabetes) | Baseline (week 0), end of treatment (week 72) | Number of participants with change in glycaemic category from baseline (week 0) to the end of treatment (week 72) is presented. These categories were set as per the following criteria: 1) Normo-glycaemia: glycated haemoglobin (HbA1c) \<5.7%; 2) Pre-diabetes: 5.7% \<= HbA1c \< 6.5% |
| Semaglutide 7.2 mg Versus Placebo: Number of Adverse Events (AEs) | From baseline (week 0) to end of study (week 81) | Number of AEs is reported. An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. |
| Semaglutide 7.2 mg Versus Placebo: Number of Serious Adverse Events (SAEs) | From baseline (week 0) to end of study (week 81) | Number of SAEs is reported. A SAE is any untoward medical occurrence that fulfils at least one of the following criteria: results in death, is life threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical event. |
| Semaglutide 7.2 mg Versus Placebo: Change in Pulse | Baseline (week 0), End of treatment (week 72) | Change in pulse from baseline (week 0) to end of treatment (week 72) is presented. |
| Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of AEs | From baseline (week 0) to end of study (week 81) | Number of AEs is reported. An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of IMP, whether or not considered related to the IMP. |
| Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of SAEs | From baseline (week 0) to end of study (week 81) | Number of SAEs is reported. A SAE is any untoward medical occurrence that fulfils at least one of the following criteria: results in death, is life threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical event. |
Countries
Bulgaria, Canada, Czechia, Germany, Greece, Hungary, Norway, Poland, Portugal, Slovakia, South Africa, United States
Contacts
STUDY_DIRECTORClinical Transparency (dept. 2834)
Novo Nordisk A/S
Participant flow
Recruitment details
The trial was conducted at 90 sites in 11 countries as follows: Bulgaria, Canada, Germany, Greece, Hungary, Norway, Poland, Portugal, Slovakia, South Africa, and the Unites States.
Pre-assignment details
The trial included a treatment period of 72 weeks (20 weeks of dose escalation and 52 weeks of maintenance period) followed by 9-week follow-up period. Participants were randomized in 5:1:1 ratio in either semaglutide 7.2 milligrams (mg), semaglutide 2.4 mg or placebo as an adjunct to reduced-calorie diet and increased physical activity.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 47 Years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 189 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1203 Participants |
| Sex: Female, Male Female | 1037 Participants |
| Sex: Female, Male Male | 252 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1,005 | 0 / 201 | 0 / 201 |
| other Total, other adverse events | 784 / 1,004 | 140 / 201 | 117 / 201 |
| serious Total, serious adverse events | 73 / 1,004 | 22 / 201 | 11 / 201 |
Outcome results
None listed