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Phase 3 Completed N=401 Randomized Quadruple-blind Treatment

STEP 6: Research Study Investigating How Well Semaglutide Works in People Living With Overweight or Obesity

Source: ClinicalTrials.gov NCT03811574 ↗
Enrolled (actual)
401
Serious AEs
6.0%
Results posted
Mar 2022
Primary outcomePrimary: Change in Body Weight (%) — -9.9; -13.4; -1.9 Percentage change — p=<.0001
◆ Published Evidence
Highly cited
1,262citations · ~252 / year
Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial.
Lancet (London, England) · 2021 · Open access · High-confidence link

Summary

This study will look at the change in participants' body weight from the start to the end of the study. This is to compare the effect on body weight in people taking semaglutide (a new medicine) and people taking "dummy" medicine. In addition to taking the medicine, participants will have talks with study staff about healthy food choices, how to be more physically active and what participants can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment participants get is decided by chance. Participants are three times as likely to get semaglutide as "dummy" medicine. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skinfold in the stomach, thigh or upper arm. The study will last for about one and a half years. Participants will have 14 clinic visits and 11 phone calls with the study doctor.

Linked Publications (3)

  • Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial.
    Lancet (London, England) · 2021 · 1,262 citations · Open access · High-confidence link
  • Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial.
    The lancet. Diabetes & endocrinology · 2022 · 302 citations · Likely link
  • Effect of once-weekly subcutaneous semaglutide on abdominal visceral fat area in Japanese adults with overweight and obesity: A post hoc analysis of the STEP 6 trial.
    Obesity research & clinical practice · 2025 · 8 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Body Weight (%)
-9.9; -13.4; -1.9 <.0001 sig
PRIMARY
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%
71; 160; 21; 27; 33; 79 <.0001 sig
SECONDARY
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10%
41; 117; 5; 57; 76; 95
SECONDARY
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15%
24; 79; 3; 74; 114; 97
SECONDARY
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20%
11; 38; 2; 87; 155; 98
SECONDARY
Change in Waist Circumference Measured Midway Between the Lower Rib Margin and the Iliac Crest
-7.8; -11.2; -1.8
SECONDARY
Change in Waist Circumference Measured According to the JASSO (Japan Society for the Study of Obesity) Guideline
-7.6; -10.2; -1.9
SECONDARY
Change in Body Weight (Kg)
-8.3; -11.3; -1.7
SECONDARY
Change in Body Mass Index (BMI)
-3.1; -4.3; -0.6
SECONDARY
Change in Visceral Fat Area (VFA) (%)
-22.3; -41.0; -7.1
SECONDARY
Change in Visceral Fat Area (VFA) Centimeter Square (cm^2)
-41.7; -67.4; -13.8
SECONDARY
Change in HbA1c (%)
-0.9; -1.0; 0.0
SECONDARY
Change in HbA1c (mmol/Mol)
-9.9; -10.6; -0.1
SECONDARY
Change in Fasting Plasma Glucose
-18.3; -19.3; 1.7
SECONDARY
Change in Fasting Serum Insulin-ratio to Baseline
0.85; 0.71; 0.89
SECONDARY
Change in Systolic Blood Pressure
-12; -11; -5
SECONDARY
Change in Diastolic Blood Pressure
-5; -5; -3
SECONDARY
Change in Total Cholesterol-ratio to Baseline
0.93; 0.91; 1.00
SECONDARY
Change in High-density Lipoproteins (HDL)-Ratio to Baseline
1.06; 1.08; 1.06
SECONDARY
Change in Low-density Lipoproteins (LDL)-Ratio to Baseline
0.90; 0.86; 0.95
SECONDARY
Change in Very Low-density Lipoproteins (VLDL)-Ratio to Baseline
0.79; 0.79; 1.05
SECONDARY
Change in Free Fatty Acids-ratio to Baseline
1.04; 0.96; 1.28
SECONDARY
Change in Triglycerides-ratio to Baseline
0.78; 0.79; 1.05
SECONDARY
Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline
0.64; 0.39; 0.92
SECONDARY
Change in Plasminogen Activator Inhibitor-1 Activity-ratio to Baseline
0.83; 0.68; 1
SECONDARY
Change in Short Form 36 v2.0 Acute (SF-36) Score
0.0; 1.0; -0.5; -1.6; -0.2; 0.3
SECONDARY
Change in Impact of Weight on Quality of Life-lite for Clinical Trials (IWQOL-Lite for CT) Score
2.6; 4.9; 0.5; 1.9; 4.2; -0.8
SECONDARY
Number of Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score
19; 43; 13; 79; 149; 87
SECONDARY
Number of Participants Who Achieve (Yes/no): Responder Definition Value for IWQoL-Lite for CT Physical Function (5-items) Score
19; 49; 11; 79; 143; 89
SECONDARY
Number of Participants Who Achieved (Yes/no): HbA1c <7.0% (53 mmol/Mol)
24; 43; 1; 1; 6; 24
SECONDARY
Number of Participants Who Achieved (Yes/no): HbA1c ≤6.5% (48 mmol/Mol)
22; 40; 1; 3; 9; 24
SECONDARY
Number of Treatment-emergent AEs
483; 834; 235
SECONDARY
Number of Serious Adverse Events
10; 12; 7
SECONDARY
Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemia Episodes
0; 0; 0
SECONDARY
Change in Pulse
6; 4; 2
SECONDARY
Change in Amylase: Ratio to Baseline
1.09; 1.08; 0.93
SECONDARY
Change in Lipase: Ratio to Baseline
1.56; 1.56; 0.96
SECONDARY
Change in Calcitonin: Ratio to Baseline
0.98; 0.95; 0.94
SECONDARY
Change in QTCF Interval
-2.2; -2.5; 5.6

Eligibility Criteria

Inclusion Criteria

  • Male or female, age more than or equal to 18 years at the time of signing informed consent
  • BMI more than or equal to 27.0 kg/m^2 with more than or equal to 2 weight related comorbidities (treated or untreated) or BMI more than or equal to 35.0 kg/m^2 with more than or equal to 1 weight related comorbidity (treated or untreated) according to the JASSO guideline. At least one comorbidity should be hypertension or dyslipidaemia (Japan only: or T2D)
  • History of at least one self-reported unsuccessful dietary effort to lose body weight
  • For subjects with T2D at screening (Japan only): a) Diagnosed with T2D more than or equal to 180 days prior to the day of screening. b) HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive)

Exclusion Criteria

  • A self-reported change in body weight more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records
  • For subjects without T2D at screening: HbA1c more than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening
  • For subjects with T2D at screening (Japan only): a) Renal impairment measured as estimated glomerular filtration rate (eGFR) value of less than 30 mL/min/1.73 m^2 (less than 60 mL/min/1.73 m^2 in subjects treated with sodium-glucose co-transporter 2 inhibitor (SGLT2i)) according to chronic kidney disease epidemiology (CKD-EPI) creatinine equation as defined by kidney disease improving global outcome (KDIGO) 2012 by the central laboratory at screening. b) Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03811574) 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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