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Phase 3 Completed N=338 Randomized Quadruple-blind Treatment

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

Overweight · Obesity
Source: ClinicalTrials.gov NCT04074161 ↗
Enrolled (actual)
338
Serious AEs
8.9%
Results posted
Apr 2022
Primary outcomePrimary: Change From Baseline (Week 0) to Week 68 in Body Weight (%) (Semaglutide 2.4 mg Versus Liraglutide 3.0 mg) — -16.4; -6.4 Percentage of body weight — p=<0.0001
◆ Published Evidence
Highly cited
861citations · ~215 / year
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 · Open access · High-confidence link

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.

Linked Publications (3)

  • 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 · 861 citations · Open access · High-confidence link
  • Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: recommendations for clinical practice.
    Postgraduate medicine · 2022 · 198 citations · Open access · High-confidence link
  • 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, obesity & metabolism · 2022 · 10 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Change From Baseline (Week 0) to Week 68 in Body Weight (%) (Semaglutide 2.4 mg Versus Liraglutide 3.0 mg)
-16.4; -6.4 <0.0001 sig
SECONDARY
Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction Greater Than or Equal to (>=) 10% (Yes/no)
83; 30; 12; 34; 87; 66
SECONDARY
Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction >=15% (Yes/no)
65; 14; 5; 52; 103; 73
SECONDARY
Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction >=20% (Yes/no)
45; 7; 2; 72; 110; 76
SECONDARY
Change From Baseline (Week 0) to Week 68 in Waist Circumference
-13.6; -6.8; -2.0
SECONDARY
Change From Baseline (Week 0) to Week 68 in Body Weight (Kilograms (kg))
-15.8; -6.8; -1.4
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)
-16.4; -6.4; -1.6
SECONDARY
Change From Baseline (Week 0) to Week 68 in Systolic Blood Pressure
-7; -4; 5
SECONDARY
Change From Baseline (Week 0) to Week 68 in Diastolic Blood Pressure
-5; -1; 1
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: Total Cholesterol (Milligram Per Deciliter (mg/dL)) (Ratio to Baseline)
0.92; 1.00; 0.99
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: Total Cholesterol (Millimoles Per Liter (mmol/L)) (Ratio to Baseline)
0.92; 1.00; 0.99
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: High Density Lipoprotein (HDL) Cholesterol (mg/dL) (Ratio to Baseline)
0.99; 1.02; 0.99
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: High Density Lipoprotein (HDL) Cholesterol (mmol/L) (Ratio to Baseline)
0.99; 1.02; 0.99
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: Low Density Lipoprotein (LDL) Cholesterol (mg/dL) (Ratio to Baseline)
0.93; 1.01; 0.99
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: Low Density Lipoprotein (LDL) Cholesterol (mmol/L) (Ratio to Baseline)
0.93; 1.01; 0.99
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: Very Low Density Lipoprotein (VLDL) Cholesterol (mg/dL) (Ratio to Baseline)
0.79; 0.89; 0.97
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: Very Low Density Lipoprotein (VLDL) Cholesterol (mmol/L) (Ratio to Baseline)
0.79; 0.89; 0.97
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: Free Fatty Acids (FFA) (mg/dL) (Ratio to Baseline)
0.90; 0.87; 1.10
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: Free Fatty Acids (FFA) (mmol/L) (Ratio to Baseline)
0.90; 0.87; 1.10
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: Triglycerides (mg/dL) (Ratio to Baseline)
0.80; 0.89; 0.98
SECONDARY
Change From Baseline (Week 0) to Week 68 in Lipids: Triglycerides (mmol/L) (Ratio to Baseline)
0.80; 0.89; 0.98
SECONDARY
Change From Baseline (Week 0) to Week 68 in High-sensitivity C-reactive Protein (Hs-CRP): Ratio to Baseline
0.46; 0.73; 0.78
SECONDARY
Change From Baseline (Week 0) to Week 68 in Glycated Haemoglobin (HbA1c) (%)
-0.3; -0.1; 0.1
SECONDARY
Change From Baseline (Week 0) to Week 68 in Glycated Haemoglobin (HbA1c) (Millimoles Per Mole (mmol/Mol))
-2.8; -1.0; 1.2
SECONDARY
Change From Baseline (Week 0) to Week 68 in Fasting Plasma Glucose (mg/dL)
-9.0; -4.9; 2.4
SECONDARY
Change From Baseline (Week 0) to Week 68 in Fasting Plasma Glucose (mmol/L)
-0.5; -0.3; 0.1
SECONDARY
Change From Baseline (Week 0) to Week 68 in Fasting Serum Insulin (Milli-international Units Per Liter (mIU/L)): Ratio to Baseline
0.73; 0.85; 0.98
SECONDARY
Change From Baseline (Week 0) to Week 68 in Fasting Serum Insulin (Picomoles Per Liter (Pmol/L)): Ratio to Baseline
0.73; 0.85; 0.98
SECONDARY
Number of Participants at Baseline (Week 0) and Week 68 in Glycaemic Category (Normo-glycaemia, Pre-diabetes, Type 2 Diabetes (T2D))
72; 74; 47; 38; 37; 30
SECONDARY
Number of Participants Who From Baseline (Week 0) to Week 68 Permanently Discontinued Randomized Trial Product
17; 35; 15
SECONDARY
Number of Treatment Emergent Adverse Events (TEAEs) From Baseline (Week 0) to Week 75
904; 823; 522
SECONDARY
Number of Serious Adverse Events (SAEs) From Baseline (Week 0) to Week 75
14; 18; 9

Eligibility 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04074161) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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