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Phase 3 Completed N=1,961 Randomized Quadruple-blind Treatment

STEP 1: Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity

Metabolism and Nutrition Disorder · Overweight or Obesity
Source: ClinicalTrials.gov NCT03548935 ↗
Enrolled (actual)
1,961
Serious AEs
8.7%
Results posted
Aug 2021
Primary outcomePrimary: Change in Body Weight (%) — -15.6; -2.8; -16.9; -3.1 Percentage point — p=<.0001
◆ Published Evidence
Highly cited
4,362citations · ~872 / year
Once-Weekly Semaglutide in Adults with Overweight or Obesity.
The New England journal of medicine · 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. The weight loss in participants taking semaglutide (a new medicine) will be compared to the weight loss of participants 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 you can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment participants get, is decided by chance. Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. The study has two phases: A main phase and an extension phase.The main phase will last for about 1.5 years. Participants will have 15 clinic visits and 10 phone calls with the study doctor. Extension phase: Approximately 300 participants will continue in the extension phase in the following countries only: Canada, Germany, the UK and selected sites in the US and Japan. These participants will be in the study for about 2.5 years.They will not receive treatment, but will attend another 5 follow-up visits with the study doctor.

Linked Publications (5)

  • Once-Weekly Semaglutide in Adults with Overweight or Obesity.
    The New England journal of medicine · 2021 · 4,362 citations · Open access · High-confidence link
  • Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology: Post Hoc Analysis of the STEP 1, 2, 3, and 5 Trials.
    JAMA internal medicine · 2024 · 75 citations · Open access · Likely link
  • Impact of BMI and comorbidities on efficacy of once-weekly semaglutide: Post hoc analyses of the STEP 1 randomized trial.
    Obesity (Silver Spring, Md.) · 2023 · 11 citations · Open access · Likely link
  • Proteomic signatures reflect effects of semaglutide treatment for MASH.
    JHEP reports : innovation in hepatology · 2025 · 5 citations · Open access · Likely link
  • The Correlation Between Body Mass Index and Health-Related Quality of Life: Data from Two Weight Loss Intervention Studies.
    Advances in therapy · 2024 · 1 citation · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Body Weight (%)
-15.6; -2.8; -16.9; -3.1 <.0001 sig
PRIMARY
Participants Who Achieve 5 or More Percent Body Weight Reduction (Yes/no)
1047; 182; 165; 395; 978; 165 <0.0001 sig
SECONDARY
Subjects Who Achieve 10 or More Percent Body Weight Reduction (Yes/no)
838; 69; 374; 508
SECONDARY
Participants Who Achieve 15 or More Percent Body Weight Reduction (Yes/no)
612; 28; 600; 549
SECONDARY
Participants Who Achieve 20 or More Percent Body Weight Reduction (Yes/no)
388; 10; 824; 567
SECONDARY
Change in Waist Circumference (cm)
-14.1; -4.4
SECONDARY
Change in Systolic Blood Pressure (mmHg)
-7; -1
SECONDARY
Change in Short Form 36 (SF-36)
2.3; 0.4; 1.1; -0.2; 0.5; -1.3
SECONDARY
Change in Impact of Weight on Quality of Life-Lite for Clinical Trial (IWQoL-Lite for CT) Score
15.0; 6.0; 14.0; 5.0; 17.4; 6.9
SECONDARY
Change in Body Weight (kg)
-16.1; -2.9
SECONDARY
Change in Body Mass Index (BMI) (kg/m2)
-5.8; -1.0
SECONDARY
Change in HbA1C (%)
-0.5; -0.2
SECONDARY
Change in HbA1C (mmol/Mol)
-5.1; -1.8
SECONDARY
Change in Fasting Plasma Glucose (FPG) (mg/dL)
-9.2; -0.4
SECONDARY
Change in Fasting Serum Insulin (mIU/L) - Ratio to Baseline
0.73; 0.92
SECONDARY
Change in Diastolic Blood Pressure (mmHg)
-3; -1
SECONDARY
Change in Total Cholesterol (mg/dL) - Ratio to Baseline
0.96; 1.00
SECONDARY
Change in High-density Lipoproteins (HDL) (mg/dL) - Ratio to Baseline
1.05; 1.02
SECONDARY
Change in Low-density Lipoproteins (LDL) (mg/dL) - Ratio to Baseline
0.97; 1.01
SECONDARY
Change in Very Low-density Lipoproteins (VLDL) (mg/dL) - Ratio to Baseline
0.77; 0.92
SECONDARY
Change in Free Fatty Acids (mg/dL) - Ratio to Baseline
0.83; 0.93
SECONDARY
Change in Triglycerides (mg/dL) - Ratio to Baseline
0.77; 0.92
SECONDARY
Change in High Sensitivity C-Reactive Protein (hsCRP) - (mg/L) - Ratio to Baseline
0.45; 0.84
SECONDARY
Change in Plasminogen Activator Inhibitor-1 (PAI-1) Activity (AU/ml) - Ratio to Baseline
1.15; 1.53
SECONDARY
Change in Soluble Leptin Receptor (ng/mL) - Ratio to Baseline
1.07; 1.02
SECONDARY
Change in Leptin (ng/mL) - Ratio to Baseline
0.52; 0.87
SECONDARY
Change in Body Composition (Total Fat Mass) (%)
-3.9; -0.3
SECONDARY
Change in Body Composition (Total Fat Mass) (kg)
-9.3; -1.5
SECONDARY
Change in Body Composition (Lean Body Mass) (%)
3.4; 0.2
SECONDARY
Change in Body Composition (Lean Body Mass) (kg)
-5.8; -1.8
SECONDARY
Change in Body Composition (Visceral Fat Mass) (%)
-2.2; -0.1
SECONDARY
Change in Body Composition (Visceral Fat Mass) (kg)
-0.4; -0.1
SECONDARY
Change in Body Weight (%) - DEXA Subpopulation
-15.8; -3.4
SECONDARY
Change in Body Weight (kg) - DEXA Subpopulation
-15.5; -3.2
SECONDARY
Participants Who Achieve "Responder Definition Value" (Yes/no) for SF-36 Physical Functioning Score
318; 97; 877; 469; 478; 153
SECONDARY
Participants Who Achieve "Responder Definition Value" (Yes/no) for IWQoL-Lite for CT Physical Function Domain (5-items) Score
473; 145; 720; 421; 611; 186
SECONDARY
Number of Treatment Emergent Adverse Events (TEAEs)
9658; 3302
SECONDARY
Number of Serious Adverse Events (SAEs)
164; 53
SECONDARY
Change in Pulse
3; -1
SECONDARY
Change in Amylase - Ratio to Baseline
1.14; 1.03
SECONDARY
Change in Lipase - Ratio to Baseline
1.41; 0.97
SECONDARY
Change in Calcitonin - Ratio to Baseline
0.99; 0.95

Eligibility Criteria

Inclusion Criteria

Main phase:

  • Male or female, age greater than or equal to 18 years at the time of signing informed consent
  • Body mass index (BMI) greater than or equal to 30.0 kg/sqm or greater than or equal to 27.0 kg/sqm 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

Extension phase:

  • Informed consent for the extension phase obtained before any trial related activities for the extension phase
  • On randomised treatment on the target dose at week 68, i.e. treated with 2.4 mg semaglutide once-weekly or semaglutide placebo

Exclusion Criteria

Main phase:

  • Glycated haemoglobin (HbA1C) greater than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening
  • A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Extension phase:

  • Female who is pregnant or intends to become pregnant during the extension phase
  • Any disorder, unwillingness or inability, not covered by any of the other exclusion criteria, which in the investigator's opinion, might jeopardise the subject's compliance with the extension of the trial
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03548935) 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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