OverweightPhase 3STEP 8NCT04074161

Research Study to Investigate How Well Semaglutide Works Compared to Liraglutide in People Living With Overweight or Obesity

A Phase 3 study testing Semaglutide and Liraglutide in people with Overweight and Obesity, run by Novo Nordisk A/S at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Overweight, Obesity
What is being tested?: Semaglutide and Liraglutide
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 338 participants
Where: 19 sitesUnited States
Study dates: 11 Sep 2019to 11 May 2021
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female, age 18 years or older at the time of signing informed consent
Body mass index (BMI) equal to or above 30.0 kg/m^2 or equal to or above 27.0 kg/m^2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease
History of at least one self-reported unsuccessful dietary effort to lose body weight

Who cannot join

HbA1c equal to or above 48 mmol/mol (6.5%) as measured by the central laboratory at screening
History of type 1 or type 2 diabetes mellitus
A self-reported change in body weight of more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Trial locations and contacts

19 sites in 1 country.

City, postcode or hospital

19 sites in 1 country

United States19 sites

Novo Nordisk Investigational Site
Albany, New York, 12203
Novo Nordisk Investigational Site
Arlington, Virginia, 22206
Novo Nordisk Investigational Site
Baton Rouge, Louisiana, 70808
Novo Nordisk Investigational Site
Birmingham, Alabama, 35294
Novo Nordisk Investigational Site
Charleston, South Carolina, 29425
Novo Nordisk Investigational Site
Dallas, Texas, 75226
Novo Nordisk Investigational Site
Dallas, Texas, 75230
Novo Nordisk Investigational Site
Evanston, Illinois, 60201-2477
Novo Nordisk Investigational Site
Fullerton, California, 92835
Novo Nordisk Investigational Site
Honolulu, Hawaii, 96814
Novo Nordisk Investigational Site
Huntington Beach, California, 92648
Novo Nordisk Investigational Site
Indianapolis, Indiana, 46260
Novo Nordisk Investigational Site
Jacksonville, Florida, 32205
Novo Nordisk Investigational Site
Olympia, Washington, 98502
Novo Nordisk Investigational Site
Philadelphia, Pennsylvania, 19104-3317
Novo Nordisk Investigational Site
Plantation, Florida, 33324
Novo Nordisk Investigational Site
Rockwall, Texas, 75032
Novo Nordisk Investigational Site
Wilmington, North Carolina, 28401
Novo Nordisk Investigational Site
Winchester, Virginia, 22601-3834

Other trials in United States

About this study

Official title: Effect and Safety of Subcutaneous Semaglutide 2.4 mg Once Weekly Compared to Liraglutide 3.0 mg Once Daily on Weight Management in Subjects With Overweight or Obesity

This study will look at participants' body weight from the start to the end of the study. The study will last for about 1½ years. This is to compare the effect on body weight in people taking semaglutide once a week or people taking liraglutide once every day. Participants will either get semaglutide, liraglutide or "dummy" medicine. Which treatment is decided by chance. Participants who receive semaglutide or semaglutide "dummy" medicine will need to take 1 injection once a week. Participants who receive liraglutide or liraglutide "dummy" medicine will need to take 1 injection once daily. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. During the study participants will have talks with study staff about eating healthy food and how to be more physically active. Participants will have 16 clinic visits and 7 phone calls with the study doctor. At 4 of the clinic visits participants cannot eat and drink (water is allowed) for 8 hours before the visit. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Conditions: Overweight, Obesity
Being tested: Semaglutide, Placebo (semaglutide), Liraglutide, Placebo (liraglutide)
Medical subject headings: Overweight, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

SemaglutideDrug
Dose gradually increased to 2.4 mg administered once weekly for 68 weeks
Placebo (semaglutide)Drug
Administered once weekly for 68 weeks
LiraglutideDrug
Dose gradually increased to 3.0 mg administered once daily for 68 weeks
Placebo (liraglutide)Drug
Administered once daily for 68 weeks

Study groups in NCT04074161
Study group	Role	What they receive
Semaglutide	Experimental	Semaglutide administered s.c. (subcutaneously, under the skin) adjunct to a reduced-calorie diet and increased physical activity Receives: Drug: Semaglutide
Placebo (semaglutide)	Placebo comparator	Placebo (semaglutide) administered s.c. adjunct to a reduced-calorie diet and increased physical activity Receives: Drug: Placebo (semaglutide)
Liraglutide	Active comparator	Liraglutide administered s.c. adjunct to a reduced-calorie diet and increased physical activity Receives: Drug: Liraglutide
Placebo (liraglutide)	Placebo comparator	Placebo (liraglutide) administered s.c. adjunct to a reduced-calorie diet and increased physical activity Receives: Drug: Placebo (liraglutide)

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline (Week 0) to Week 68 in Body Weight (%) (Semaglutide 2.4 mg Versus Liraglutide 3.0 mg)
Change from baseline (week 0) to week 68 in body weight (%) is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68

Secondary outcomes (31)

Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction Greater Than or Equal to (>=) 10% (Yes/no)
Number of participants who achieved >= 10% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved >= 10% weight reduction, whereas 'No' infers the number of participants who did not achieve >= 10% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: From baseline (week 0) to week 68
Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction >=15% (Yes/no)
Number of participants who achieved >= 15% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved >= 15% weight reduction, whereas 'No' infers the number of participants who did not achieve >= 15% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: From baseline (week 0) to week 68
Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction >=20% (Yes/no)
Number of participants who achieved >= 20% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved >= 20% weight reduction, whereas 'No' infers the number of participants who did not achieve >= 20% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: From baseline (week 0) to week 68
Change From Baseline (Week 0) to Week 68 in Waist Circumference
Change from baseline (week 0) to week 68 in waist circumference is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Body Weight (Kilograms (kg))
Change from baseline (week 0) to week 68 in body weight is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Body Weight (%) (Semaglutide 2.4 mg Versus Pooled Placebo and Liraglutide 3.0 mg Versus Pooled Placebo)
Change from baseline (week 0) to week 68 in body weight (%) is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Systolic Blood Pressure
Change from baseline (week 0) to week 68 in systolic blood pressure is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Diastolic Blood Pressure
Change from baseline (week 0) to week 68 in diastolic blood pressure is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Total Cholesterol (Milligram Per Deciliter (mg/dL)) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in total cholesterol (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Total Cholesterol (Millimoles Per Liter (mmol/L)) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in total cholesterol (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: High Density Lipoprotein (HDL) Cholesterol (mg/dL) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in HDL cholesterol (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: High Density Lipoprotein (HDL) Cholesterol (mmol/L) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in HDL cholesterol (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Low Density Lipoprotein (LDL) Cholesterol (mg/dL) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in LDL cholesterol (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Low Density Lipoprotein (LDL) Cholesterol (mmol/L) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in LDL cholesterol (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Very Low Density Lipoprotein (VLDL) Cholesterol (mg/dL) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in VLDL cholesterol (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Very Low Density Lipoprotein (VLDL) Cholesterol (mmol/L) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in VLDL cholesterol (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Free Fatty Acids (FFA) (mg/dL) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in FFA (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Free Fatty Acids (FFA) (mmol/L) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in FFA (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Triglycerides (mg/dL) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in triglycerides (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Triglycerides (mmol/L) (Ratio to Baseline)
Change from baseline (week 0) to week 68 in triglycerides (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in High-sensitivity C-reactive Protein (Hs-CRP): Ratio to Baseline
Change from baseline (week 0) to week 68 in hs-CRP (measured in mg/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Glycated Haemoglobin (HbA1c) (%)
Change from baseline (week 0) to week 68 in HbA1c (%) is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Glycated Haemoglobin (HbA1c) (Millimoles Per Mole (mmol/Mol))
Change from baseline (week 0) to week 68 in HbA1c is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Fasting Plasma Glucose (mg/dL)
Change from baseline (week 0) to week 68 in fasting plasma glucose is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Fasting Plasma Glucose (mmol/L)
Change from baseline (week 0) to week 68 in fasting plasma glucose is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Fasting Serum Insulin (Milli-international Units Per Liter (mIU/L)): Ratio to Baseline
Change from baseline (week 0) to week 68 in fasting serum insulin (measured in mIU/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Fasting Serum Insulin (Picomoles Per Liter (Pmol/L)): Ratio to Baseline
Change from baseline (week 0) to week 68 in fasting serum insulin (measured in pmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Number of Participants at Baseline (Week 0) and Week 68 in Glycaemic Category (Normo-glycaemia, Pre-diabetes, Type 2 Diabetes (T2D))
Number of participants in glycaemic categories, "normo-glycaemia, pre-diabetes and type 2 diabetes" at baseline (week 0) and 68 are presented. These categories were set as per the following criteria: 1) Normo-glycaemia: fasting plasma glucose (FPG) less than (<) 5.6 mmol/L (<100 mg/dL) and/or glycated haemoglobin (HbA1c) <5.7%; 2) Pre-diabetes: FPG 5.6 - 6.9 mmol/L (both inclusive), FPG 100 - 125 mg/dL (both inclusive) or HbA1c 5.7 - 6.4% (both inclusive); 3) Type 2 diabetes: FPG greater than or equal to (>=) 7.0 mmol/L (>=126 mg/dL) and/or HbA1c >=6.5%. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Measured: Baseline (week 0), week 68
Number of Participants Who From Baseline (Week 0) to Week 68 Permanently Discontinued Randomized Trial Product
Number of participants who from baseline (week 0) to week 68 permanently discontinued randomized trial product are presented.
Measured: From baseline (week 0) to week 68
Number of Treatment Emergent Adverse Events (TEAEs) From Baseline (Week 0) to Week 75
An adverse event (AE) was any untoward medical occurrence in a clinical trial participant that was temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. All AEs mentioned here are TEAEs defined as AEs, with the onset of the event occurred in the on-treatment period. A time-point was considered on treatment if any dose of trial product has been administrated within the prior 49 days.
Measured: From baseline (week 0) to week 75
Number of Serious Adverse Events (SAEs) From Baseline (Week 0) to Week 75
An AE was any untoward medical occurrence in a clinical trial participant that was temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was defined as an AE that results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. SAEs occurred based on the on-treatment period is presented. A time-point was considered on treatment if any dose of trial product has been administrated within the prior 49 days.
Measured: From baseline (week 0) to week 75

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Sep 201911 May 2021

First posted29 Aug 2019
Study start11 Sep 2019
Primary completion27 Mar 2021
Study completion11 May 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for OverweightStudies of the same condition, open and under way.
More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 338 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04074161
Sponsor's protocol ID: NN9536-4576
Other IDs: U1111-1233-0977
Acronym: STEP 8
Status last verified: May 2023
First submitted: 28 Aug 2019
Last updated: 19 May 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Publications

Wharton S, Davies M, Dicker D, Lingvay I, Mosenzon O, Rubino DM, Pedersen SD. Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: recommendations for clinical practice. Postgrad Med. 2022 Jan;134(1):14-19. doi: 10.1080/00325481.2021.2002616. Epub 2021 Nov 29.
PubMed 34775881
Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sorrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150. doi: 10.1001/jama.2021.23619.
PubMed 35015037
Snitker S, Egebjerg C, Frederiksen M, Sparre T. Ease-of-use and acceptability of the novel semaglutide 2.4 mg single-dose pen-injector in people with overweight or obesity in the STEP 8 phase III trial. Diabetes Obes Metab. 2022 Nov;24(11):2273-2276. doi: 10.1111/dom.14809. Epub 2022 Aug 7. No abstract available.
PubMed 35791625

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect and Safety of Subcutaneous Semaglutide 2.4 mg Once Weekly Compared to Liraglutide 3.0 mg Once Daily on Weight Management in Subjects With Overweight or Obesity
ClinicalTrials.gov ID: NCT04074161
Acronym / sponsor ID: STEP 8 / NN9536-4576
Conditions: Overweight, Obesity
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 338 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: 11 Sep 2019 (actual)
Primary completion: 27 Mar 2021 (actual)
Study completion: 11 May 2021 (actual)
First posted: 29 Aug 2019 (actual)
Results: Posted 27 Apr 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Semaglutide	Experimental	Drug: SemaglutideSemaglutide administered s.c. (subcutaneously, under the skin) adjunct to a reduced-calorie diet and increased physical activity
Placebo (semaglutide)	Placebo comparator	Drug: Placebo (semaglutide)Placebo (semaglutide) administered s.c. adjunct to a reduced-calorie diet and increased physical activity
Liraglutide	Active comparator	Drug: LiraglutideLiraglutide administered s.c. adjunct to a reduced-calorie diet and increased physical activity
Placebo (liraglutide)	Placebo comparator	Drug: Placebo (liraglutide)Placebo (liraglutide) administered s.c. adjunct to a reduced-calorie diet and increased physical activity

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Male or female, age 18 years or older at the time of signing informed consent
Body mass index (BMI) equal to or above 30.0 kg/m^2 or equal to or above 27.0 kg/m^2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease
History of at least one self-reported unsuccessful dietary effort to lose body weight

Key exclusion criteria (3 listed)

HbA1c equal to or above 48 mmol/mol (6.5%) as measured by the central laboratory at screening
History of type 1 or type 2 diabetes mellitus
A self-reported change in body weight of more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
SemaglutideDose gradually increased to 2.4 mg administered once weekly for 68 weeks	Drug	Semaglutide
Placebo (semaglutide)Administered once weekly for 68 weeks	Drug	Placebo (semaglutide)
LiraglutideDose gradually increased to 3.0 mg administered once daily for 68 weeks	Drug	Liraglutide
Placebo (liraglutide)Administered once daily for 68 weeks	Drug	Placebo (liraglutide)

Primary outcome

Change From Baseline (Week 0) to Week 68 in Body Weight (%) (Semaglutide 2.4 mg Versus Liraglutide 3.0 mg)
Time frame: Baseline (week 0), week 68
Change from baseline (week 0) to week 68 in body weight (%) is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.

31 secondary outcomes

Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction Greater Than or Equal to (>=) 10% (Yes/no)
Time frame: From baseline (week 0) to week 68
Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction >=15% (Yes/no)
Time frame: From baseline (week 0) to week 68
Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction >=20% (Yes/no)
Time frame: From baseline (week 0) to week 68
Change From Baseline (Week 0) to Week 68 in Waist Circumference
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Body Weight (Kilograms (kg))
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Body Weight (%) (Semaglutide 2.4 mg Versus Pooled Placebo and Liraglutide 3.0 mg Versus Pooled Placebo)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Systolic Blood Pressure
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Diastolic Blood Pressure
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Total Cholesterol (Milligram Per Deciliter (mg/dL)) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Total Cholesterol (Millimoles Per Liter (mmol/L)) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: High Density Lipoprotein (HDL) Cholesterol (mg/dL) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: High Density Lipoprotein (HDL) Cholesterol (mmol/L) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Low Density Lipoprotein (LDL) Cholesterol (mg/dL) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Low Density Lipoprotein (LDL) Cholesterol (mmol/L) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Very Low Density Lipoprotein (VLDL) Cholesterol (mg/dL) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Very Low Density Lipoprotein (VLDL) Cholesterol (mmol/L) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Free Fatty Acids (FFA) (mg/dL) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Free Fatty Acids (FFA) (mmol/L) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Triglycerides (mg/dL) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Lipids: Triglycerides (mmol/L) (Ratio to Baseline)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in High-sensitivity C-reactive Protein (Hs-CRP): Ratio to Baseline
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Glycated Haemoglobin (HbA1c) (%)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Glycated Haemoglobin (HbA1c) (Millimoles Per Mole (mmol/Mol))
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Fasting Plasma Glucose (mg/dL)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Fasting Plasma Glucose (mmol/L)
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Fasting Serum Insulin (Milli-international Units Per Liter (mIU/L)): Ratio to Baseline
Time frame: Baseline (week 0), week 68
Change From Baseline (Week 0) to Week 68 in Fasting Serum Insulin (Picomoles Per Liter (Pmol/L)): Ratio to Baseline
Time frame: Baseline (week 0), week 68
Number of Participants at Baseline (Week 0) and Week 68 in Glycaemic Category (Normo-glycaemia, Pre-diabetes, Type 2 Diabetes (T2D))
Time frame: Baseline (week 0), week 68
Number of Participants Who From Baseline (Week 0) to Week 68 Permanently Discontinued Randomized Trial Product
Time frame: From baseline (week 0) to week 68
Number of Treatment Emergent Adverse Events (TEAEs) From Baseline (Week 0) to Week 75
Time frame: From baseline (week 0) to week 75
Number of Serious Adverse Events (SAEs) From Baseline (Week 0) to Week 75
Time frame: From baseline (week 0) to week 75

Results and safety

Results posted to the registry on 27 Apr 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Semaglutide 2.4 mg	126	120
Liraglutide 3.0 mg	127	118
Pooled Placebo	85	81

Primary outcome: Change From Baseline (Week 0) to Week 68 in Body Weight (%) (Semaglutide 2.4 mg Versus Liraglutide 3.0 mg)

Time frame: Baseline (week 0), week 68. Mean (Standard Deviation). Unit: Percentage of body weight

Measure	Semaglutide 2.4 mg n = 117	Liraglutide 3.0 mg n = 117
Value	-16.4 (10.5)	-6.4 (7.7)

Semaglutide 2.4 mg vs Liraglutide 3.0 mg: Treatment difference: -9.38 (95% CI -11.97 to -6.80), p <0.0001, ANCOVA

Population analysed: The full analysis set (FAS) included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure. It was planned to report data only for arms 'semaglutide 2.4 mg and liraglutide 3.0 mg' for this outcome measure.

31 secondary outcomes are reported in the full results.

Adverse events

Time frame: From week 0 to week 75. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Semaglutide 2.4 mg	10 of 126 (7.9%)	115 of 126 (91.3%)	0 of 126
Liraglutide 3.0 mg	14 of 127 (11%)	115 of 127 (90.6%)	0 of 127
Pooled Placebo	6 of 85 (7.1%)	68 of 85 (80%)	0 of 85

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 34775881Wharton S, Davies M, Dicker D, Lingvay I, Mosenzon O, Rubino DM, Pedersen SD. Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: recommendations for clinical practice. Postgrad Med. 2022 Jan;134(1):14-19. doi: 10.1080/00325481.2021.2002616. Epub 2021 Nov 29.
Results publication: PubMed 35015037Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sorrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150. doi: 10.1001/jama.2021.23619.
Derived from this study: PubMed 35791625Snitker S, Egebjerg C, Frederiksen M, Sparre T. Ease-of-use and acceptability of the novel semaglutide 2.4 mg single-dose pen-injector in people with overweight or obesity in the STEP 8 phase III trial. Diabetes Obes Metab. 2022 Nov;24(11):2273-2276. doi: 10.1111/dom.14809. Epub 2022 Aug 7. No abstract available.
Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Reporting Anchor and Disclosure (1452) study director

Novo Nordisk A/S

19 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Semaglutide and Liraglutide in people with Overweight and Obesity, run by Novo Nordisk A/S at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline (Week 0) to Week 68 in Body Weight (%) (Semaglutide 2.4 mg Versus Liraglutide 3.0 mg) (time frame: Baseline (week 0), week 68). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04074161, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2023.