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

Obesity Clinical Trial

— STEP 8  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04074161
• Other study ID #: NN9536-4576
• Secondary ID: U1111-1233-0977
• Status: Completed
• Phase: Phase 3
• Start date: September 11, 2019
• Est. completion date: May 11, 2021

Study information

• Verified date: May 2023
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 338
• Est. completion date: May 11, 2021
• Est. primary completion date: March 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Obesity
• Overweight

Intervention

Drug:
• Semaglutide
Dose gradually increased to 2.4 mg administered once weekly for 68 weeks
• Placebo (semaglutide)
Administered once weekly for 68 weeks
• Liraglutide
Dose gradually increased to 3.0 mg administered once daily for 68 weeks
• Placebo (liraglutide)
Administered once daily for 68 weeks

Locations

Country	Name	City	State
United States	Novo Nordisk Investigational Site	Albany	New York
United States	Novo Nordisk Investigational Site	Arlington	Virginia
United States	Novo Nordisk Investigational Site	Baton Rouge	Louisiana
United States	Novo Nordisk Investigational Site	Birmingham	Alabama
United States	Novo Nordisk Investigational Site	Charleston	South Carolina
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Evanston	Illinois
United States	Novo Nordisk Investigational Site	Fullerton	California
United States	Novo Nordisk Investigational Site	Honolulu	Hawaii
United States	Novo Nordisk Investigational Site	Huntington Beach	California
United States	Novo Nordisk Investigational Site	Indianapolis	Indiana
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Olympia	Washington
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Plantation	Florida
United States	Novo Nordisk Investigational Site	Rockwall	Texas
United States	Novo Nordisk Investigational Site	Wilmington	North Carolina
United States	Novo Nordisk Investigational Site	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

References & Publications (2)

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: — View Citation

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: 10.1080/003254 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline (week 0), week 68
Secondary	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.	From baseline (week 0) to week 68
Secondary	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.	From baseline (week 0) to week 68
Secondary	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.	From baseline (week 0) to week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	Baseline (week 0), week 68
Secondary	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.	From baseline (week 0) to week 68
Secondary	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.	From baseline (week 0) to week 75
Secondary	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.	From baseline (week 0) to week 75