Research Study to Investigate How Well Semaglutide Works Compared to Liraglutide in People Living With Overweight or Obesity (STEP 8)

• ClinicalTrials.gov Identifier: NCT04074161
• Recruitment Status: Completed
• First Posted: August 29, 2019
• Results First Posted: April 27, 2022
• Last Update Posted: May 19, 2023
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Overweight; Obesity	Drug: Semaglutide; Drug: Placebo (semaglutide); Drug: Liraglutide; Drug: Placebo (liraglutide)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 338 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description

Semaglutide once weekly vs liraglutide once daily treatment will be open label, but each of the two active treatment arms will be double blinded against placebo administered at the same dosing frequency.

Sponsor staff involved in the clinical trial is masked according to company standard procedures.

• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 11, 2019
• Actual Primary Completion Date: March 27, 2021
• Actual Study Completion Date: May 11, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Semaglutide; Semaglutide administered s.c. (subcutaneously, under the skin) adjunct to a reduced-calorie diet and increased physical activity	Drug: Semaglutide; Dose gradually increased to 2.4 mg administered once weekly for 68 weeks
Placebo Comparator: Placebo (semaglutide); Placebo (semaglutide) administered s.c. adjunct to a reduced-calorie diet and increased physical activity	Drug: Placebo (semaglutide); Administered once weekly for 68 weeks
Active Comparator: Liraglutide; Liraglutide administered s.c. adjunct to a reduced-calorie diet and increased physical activity	Drug: Liraglutide; Dose gradually increased to 3.0 mg administered once daily for 68 weeks
Placebo Comparator: Placebo (liraglutide); Placebo (liraglutide) administered s.c. adjunct to a reduced-calorie diet and increased physical activity	Drug: Placebo (liraglutide); Administered once daily for 68 weeks

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

1. 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 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.
2. 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 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.
3. 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 ]
   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.
4. 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 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.
5. 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 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.
6. 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 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.
7. 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 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.
8. 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 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.
9. 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 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.
10. 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 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.
11. 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 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.
12. 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 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.
13. 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 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.
14. 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 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.
15. 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 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.
16. 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 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.
17. 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 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.
18. 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 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.
19. 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 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.
20. 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 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.
21. 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 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.
22. 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 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.
23. 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 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.
24. 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 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.
25. 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 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.
26. 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 (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.
27. 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 ]
    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.
28. 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 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.
29. 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 participants who from baseline (week 0) to week 68 permanently discontinued randomized trial product are presented.
30. Number of Treatment Emergent Adverse Events (TEAEs) From Baseline (Week 0) to Week 75 [ Time Frame: 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.
31. Number of Serious Adverse Events (SAEs) From Baseline (Week 0) to Week 75 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Contacts and Locations

Locations

United States, Alabama

Novo Nordisk Investigational Site

Birmingham, Alabama, United States, 35294

United States, California

Novo Nordisk Investigational Site

Fullerton, California, United States, 92835

Novo Nordisk Investigational Site

Huntington Beach, California, United States, 92648

United States, Florida

Novo Nordisk Investigational Site

Jacksonville, Florida, United States, 32205

Novo Nordisk Investigational Site

Plantation, Florida, United States, 33324

United States, Hawaii

Novo Nordisk Investigational Site

Honolulu, Hawaii, United States, 96814

United States, Illinois

Novo Nordisk Investigational Site

Evanston, Illinois, United States, 60201-2477

United States, Indiana

Novo Nordisk Investigational Site

Indianapolis, Indiana, United States, 46260

United States, Louisiana

Novo Nordisk Investigational Site

Baton Rouge, Louisiana, United States, 70808

United States, New York

Novo Nordisk Investigational Site

Albany, New York, United States, 12203

United States, North Carolina

Novo Nordisk Investigational Site

Wilmington, North Carolina, United States, 28401

United States, Pennsylvania

Novo Nordisk Investigational Site

Philadelphia, Pennsylvania, United States, 19104-3317

United States, South Carolina

Novo Nordisk Investigational Site

Charleston, South Carolina, United States, 29425

United States, Texas

Novo Nordisk Investigational Site

Dallas, Texas, United States, 75226

Novo Nordisk Investigational Site

Dallas, Texas, United States, 75230

Novo Nordisk Investigational Site

Rockwall, Texas, United States, 75032

United States, Virginia

Novo Nordisk Investigational Site

Arlington, Virginia, United States, 22206

Novo Nordisk Investigational Site

Winchester, Virginia, United States, 22601-3834

United States, Washington

Novo Nordisk Investigational Site

Olympia, Washington, United States, 98502

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452); Novo Nordisk A/S

  Study Documents (Full-Text)

Documents provided by Novo Nordisk A/S:

Study Protocol  [PDF] November 25, 2020

Statistical Analysis Plan  [PDF] July 8, 2021

More Information

Publications of Results:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT04074161
• Other Study ID Numbers: NN9536-4576; U1111-1233-0977 ( Other Identifier: World Health Organization (WHO) )
• First Posted: August 29, 2019
• Results First Posted: April 27, 2022
• Last Update Posted: May 19, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://novonordisk-trials.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Liraglutide; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists