STEP 4

CompletedPhase 3Results posted

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

Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity Who Have Reached Target Dose During run-in Period

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Subcutaneous · GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

902

actual

Study population

Obesity / overweight

Key I/E criterion

•BMI ≥30

Primary endpoint

•Body weight, % change

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT03548987

Org study IDNN9536-4376

Secondary ID2017-003473-34European Medicines Agency (EudraCT)

Secondary IDU1111-1201-0898World Health Organization (WHO)

Timeline

Milestones

Study start2018-06-04actual

Study first posted2018-06-07actual

Primary completion2020-02-22actual

Study completion2020-03-20actual

Results first posted2021-03-15actual

Last update posted2022-01-19actual

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Obesity / overweight

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Male or female, age greater than or equal to 18 years at the time of signing informed consent

•Body mass index greater than or equal to 30 kg/sqm or greater than or equal to 27 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

Exclusion criteria

•Haemoglobin A1c greater than or equal to 48 mmol/mol (6.5%) as measured by central laboratory at screening

•A self-reported change in body weight more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Endpoints (74)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Weight & body composition

Cardiometabolic biomarkers

Safety / tolerability / PK

Glycemic / diabetes

Patient-reported / QoL

Weight & body composition

20 endpoints

Primary/registry result

Change From Randomisation to Week 68 in Body Weight (%)

Time frame:Randomisation (week 20) to week 68

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage point	95% CI
Semaglutide 2.4 mgIn-trial	-8.3	—
On-treatment	-8.8	—
PlaceboIn-trial	6.5	—
On-treatment	6.1	—

Treatment difference-14.7595% CI-16.00 – -13.50p<0.0001ANCOVA

Treatment policy estimand

Treatment difference-15.3395% CI-16.52 – -14.13p<0.0001MMRM (mixed model repeated measurement)

Hypothetical estimand

Primary/protocol endpoint

Change From Randomisation to Week 68 in Body Weight (%)

Time frame:Randomisation (week 20) to week 68

Body weight, % change

percent change from baseline, improvement

Secondary/registry result

Change in Waist Circumference

Time frame:Randomization (week 20) to week 68

Waist circumference, change

change from baseline, improvement

Posted result

Group	Value (mean), Centimeter (cm)	95% CI
Semaglutide 2.4 mg	-6.9	—
Placebo	3.2	—

Secondary/registry result

Change in Body Weight [Kilogram (Kg)]

Time frame:Randomisation (week 20) to week 68

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (mean), Kg	95% CI
Semaglutide 2.4 mg	-7.5	—
Placebo	5.7	—

Secondary/registry result

Change in Body Mass Index (BMI)

Time frame:Randomization (week 20) to week 68

BMI, change

change from baseline, improvement

Posted result

Group	Value (mean), Kilogram per square meter (kg/sqm)	95% CI
Semaglutide 2.4 mg	-2.7	—
Placebo	2.0	—

Secondary/registry result

Subjects Who Gain Weight (Yes/no)

Time frame:Randomisation (week 20) to week 68

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	79	—
No	441	—
PlaceboYes	206	—
No	44	—

Secondary/registry result

Change in Body Weight

Time frame:Run-in (week 0) to week 68

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage point	95% CI
Semaglutide 2.4 mg	-17.7	—
Placebo	-5.4	—

Secondary/registry result

Subjects Who Achieve (Yes/no): Body Weight Reduction < 0%

Time frame:Run-in (week 0) to week 68

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	22	—
No	498	—
PlaceboYes	51	—
No	199	—

Secondary/registry result

Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5%

Time frame:Run-in (week 0) to week 68

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	461	—
No	59	—
PlaceboYes	119	—
No	131	—

Secondary/registry result

Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10%

Time frame:Run-in (week 0) to week 68

≥10% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	411	—
No	109	—
PlaceboYes	51	—
No	199	—

Secondary/registry result

Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15%

Time frame:Run-in (week 0) to week 68

≥15% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	331	—
No	189	—
PlaceboYes	23	—
No	227	—

Secondary/protocol endpoint

Change in Waist Circumference

Time frame:Randomization (week 20) to week 68

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight [Kilogram (Kg)]

Time frame:Randomisation (week 20) to week 68

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Mass Index (BMI)

Time frame:Randomization (week 20) to week 68

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Subjects Who Gain Weight (Yes/no)

Time frame:Randomisation (week 20) to week 68

categorical status, improvement

Secondary/protocol endpoint

Change in Body Weight

Time frame:Run-in (week 0) to week 68

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Subjects Who Achieve (Yes/no): Body Weight Reduction < 0%

Time frame:Run-in (week 0) to week 68

threshold achievement, improvement

Secondary/protocol endpoint

Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5%

Time frame:Run-in (week 0) to week 68

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10%

Time frame:Run-in (week 0) to week 68

≥10% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15%

Time frame:Run-in (week 0) to week 68

≥15% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

10 endpoints

Secondary/registry result

Change in Haemoglobin A1c (HbA1c) [%]

Time frame:Randomization (week 20) to week 68

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (mean), Percentage point of HbA1c	95% CI
Semaglutide 2.4 mg	-0.2	—
Placebo	0.1	—

Secondary/registry result

Change in HbA1c [Millimoles Per Mole (mmol/Mol)]

Time frame:Randomization (week 20) to week 68

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (mean), mmol/mol	95% CI
Semaglutide 2.4 mg	-1.7	—
Placebo	1.2	—

Secondary/registry result

Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)]

Time frame:Randomization (week 20) to week 68

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (mean), mg/dL	95% CI
Semaglutide 2.4 mg	-1.1	—
Placebo	7.6	—

Secondary/registry result

Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)]

Time frame:Randomization (week 20) to week 68

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (mean), mmol/L	95% CI
Semaglutide 2.4 mg	-0.1	—
Placebo	0.4	—

Secondary/registry result

Change in Fasting Serum Insulin

Time frame:Randomization (week 20) to week 68

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of fasting serum insulin	95% CI
Semaglutide 2.4 mg	0.81	—
Placebo	1.03	—

Secondary/protocol endpoint

Change in Haemoglobin A1c (HbA1c) [%]

Time frame:Randomization (week 20) to week 68

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in HbA1c [Millimoles Per Mole (mmol/Mol)]

Time frame:Randomization (week 20) to week 68

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)]

Time frame:Randomization (week 20) to week 68

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)]

Time frame:Randomization (week 20) to week 68

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in Fasting Serum Insulin

Time frame:Randomization (week 20) to week 68

ratio, improvement

Cardiometabolic biomarkers

20 endpoints

Secondary/registry result

Change in Systolic Blood Pressure

Time frame:Randomization (week 20) to week 68

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Posted result

Group	Value (mean), Millimeters of mercury (mmHg)	95% CI
Semaglutide 2.4 mg	0	—
Placebo	5	—

Secondary/registry result

Change in Diastolic Blood Pressure

Time frame:Randomization (week 20) to week 68

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Posted result

Group	Value (mean), mmHg	95% CI
Semaglutide 2.4 mg	0	—
Placebo	1	—

Secondary/registry result

Change in Total Cholesterol

Time frame:Randomization (week 20) to week 68

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Posted result

Group	Value (geometric_mean), Ratio of fasting total cholesterol	95% CI
Semaglutide 2.4 mg	1.05	—
Placebo	1.11	—

Secondary/registry result

Change in High-density Lipoproteins (HDL)

Time frame:Randomization (week 20) to week 68

HDL-C, change

ratio, improvement

LOINC 2085-9

Posted result

Group	Value (geometric_mean), Ratio of fasting HDL cholesterol	95% CI
Semaglutide 2.4 mg	1.18	—
Placebo	1.18	—

Secondary/registry result

Change in Low-density Lipoproteins (LDL)

Time frame:Randomization (week 20) to week 68

LDL-C, change

ratio, improvement

LOINC 13457-7

Posted result

Group	Value (geometric_mean), Ratio of fasting LDL cholesterol	95% CI
Semaglutide 2.4 mg	1.01	—
Placebo	1.07	—

Secondary/registry result

Change in Very Low-density Lipoproteins (VLDL)

Time frame:Randomization (week 20) to week 68

VLDL, change

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of fasting VLDL	95% CI
Semaglutide 2.4 mg	0.94	—
Placebo	1.12	—

Secondary/registry result

Change in Free Fatty Acids

Time frame:Randomization (week 20) to week 68

Free fatty acids, change

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of fasting free fatty acids	95% CI
Semaglutide 2.4 mg	0.78	—
Placebo	0.89	—

Secondary/registry result

Change in Triglycerides

Time frame:Randomization (week 20) to week 68

Triglycerides, change

ratio, improvement

LOINC 2571-8

Posted result

Group	Value (geometric_mean), Ratio of fasting triglycerides	95% CI
Semaglutide 2.4 mg	0.94	—
Placebo	1.12	—

Secondary/registry result

Change in Pulse

Time frame:Run-in (week 0) to randomisation (week 20)

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (mean), beats per minute (bpm)	95% CI
Semaglutide 2.4 mg	5	—
Placebo	5	—

Secondary/registry result

Change in Pulse

Time frame:Randomisation (week 20) to week 68

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (mean), bpm	95% CI
Semaglutide 2.4 mg	-2	—
Placebo	-5	—

Secondary/protocol endpoint

Change in Systolic Blood Pressure

Time frame:Randomization (week 20) to week 68

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Change in Diastolic Blood Pressure

Time frame:Randomization (week 20) to week 68

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Secondary/protocol endpoint

Change in Total Cholesterol

Time frame:Randomization (week 20) to week 68

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Secondary/protocol endpoint

Change in High-density Lipoproteins (HDL)

Time frame:Randomization (week 20) to week 68

HDL-C, change

ratio, improvement

LOINC 2085-9

Secondary/protocol endpoint

Change in Low-density Lipoproteins (LDL)

Time frame:Randomization (week 20) to week 68

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in Very Low-density Lipoproteins (VLDL)

Time frame:Randomization (week 20) to week 68

VLDL, change

ratio, improvement

Secondary/protocol endpoint

Change in Free Fatty Acids

Time frame:Randomization (week 20) to week 68

Free fatty acids, change

ratio, improvement

Secondary/protocol endpoint

Change in Triglycerides

Time frame:Randomization (week 20) to week 68

Triglycerides, change

ratio, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change in Pulse

Time frame:Run-in (week 0) to randomisation (week 20)

Heart rate, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Pulse

Time frame:Randomisation (week 20) to week 68

Heart rate, change

change from baseline, improvement

Patient-reported / QoL

4 endpoints

Secondary/registry result

Change in Physical Functioning Score (Short Form 36 [SF-36])

Time frame:Randomization (week 20) to week 68

SF-36 physical

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a scale	95% CI
Semaglutide 2.4 mgChange in physical functioning score (SF-36)	1.0	—
Change in SF-36 role-physical score	0.3	—
Change in SF-36 bodily pain score	0.5	—
Change in SF-36 general health score	0.3	—
Change in SF-36 vitality score	1.1	—
Change in SF-36 social functioning score	0.1	—
Change in SF-36 mental health score	0.2	—
Change in SF-36 physical component summary	0.8	—
Change in SF-36 mental component summary	0.0	—
Change in SF-36 role-emotional score	0.0	—
PlaceboChange in physical functioning score (SF-36)	-1.2	—
Change in SF-36 role-physical score	-0.9	—
Change in SF-36 bodily pain score	-1.5	—
Change in SF-36 general health score	-1.8	—
Change in SF-36 vitality score	-2.1	—
Change in SF-36 social functioning score	-1.8	—
Change in SF-36 mental health score	-2.2	—
Change in SF-36 physical component summary	-0.9	—
Change in SF-36 mental component summary	-2.4	—
Change in SF-36 role-emotional score	-2.2	—

Secondary/registry result

Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score

Time frame:Randomisation (week 20) to week 68

SF-36 physical

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	58	—
No	457	—
PlaceboYes	11	—
No	234	—

Secondary/protocol endpoint

Change in Physical Functioning Score (Short Form 36 [SF-36])

Time frame:Randomization (week 20) to week 68

SF-36 physical

change from baseline, improvement

Secondary/protocol endpoint

Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score

Time frame:Randomisation (week 20) to week 68

SF-36 physical

threshold achievement, improvement

Safety / tolerability / PK

20 endpoints

Secondary/registry result

Number of Treatment-emergent Adverse Events (AEs)

Time frame:Run-in (week 0) to randomisation (week 20)

Treatment-emergent AEs (any)

event count, event

Posted result

Group	Value (number), Events	95% CI
Semaglutide 2.4 mg	3775	—

Secondary/registry result

Number of Treatment-emergent AEs

Time frame:Randomisation (week 20) to week 75

Treatment-emergent AEs (any)

event count, event

Posted result

Group	Value (number), Events	95% CI
Semaglutide 2.4 mg	1885	—
Placebo	779	—

Secondary/registry result

Number of Serious Adverse Events (SAEs)

Time frame:Run-in (week 0) to randomisation (week 20)

Serious AEs (any)

event count, event

Posted result

Group	Value (number), Events	95% CI
Semaglutide 2.4 mg	23	—

Secondary/registry result

Number of Serious Adverse Events (SAEs)

Time frame:Randomisation (week 20) to week 75

Serious AEs (any)

event count, event

Posted result

Group	Value (number), Events	95% CI
Semaglutide 2.4 mg	51	—
Placebo	19	—

Secondary/registry result

Change in Amylase

Time frame:Run-in (week) 0 to randomization (week 20)

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of amylase	95% CI
Semaglutide 2.4 mg	1.06	—
Placebo	1.02	—

Secondary/registry result

Change in Amylase

Time frame:Randomisation (week 20) to week 68

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of amylase	95% CI
Semaglutide 2.4 mg	1.06	—
Placebo	1.00	—

Secondary/registry result

Change in Lipase

Time frame:Run-in (week 0) to randomization (week 20)

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of lipase	95% CI
Semaglutide 2.4 mg	1.44	—
Placebo	1.39	—

Secondary/registry result

Change in Lipase

Time frame:Randomisation (week 20) to week 68

ratio, descriptive

Posted result

Group	Value (geometric_mean), ratio of lipase	95% CI
Semaglutide 2.4 mg	0.94	—
Placebo	0.68	—

Secondary/registry result

Change in Calcitonin

Time frame:Run-in (week 0) to randomization (week 20)

Thyroid event

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of Calcitonin	95% CI
Semaglutide 2.4 mg	0.98	—
Placebo	0.96	—

Secondary/registry result

Change in Calcitonin

Time frame:Randomisation (week 20) to week 68

Thyroid event

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of Calcitonin	95% CI
Semaglutide 2.4 mg	1.00	—
Placebo	0.95	—

Secondary/protocol endpoint

Number of Treatment-emergent Adverse Events (AEs)

Time frame:Run-in (week 0) to randomisation (week 20)

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

Number of Treatment-emergent AEs

Time frame:Randomisation (week 20) to week 75

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

Number of Serious Adverse Events (SAEs)

Time frame:Run-in (week 0) to randomisation (week 20)

Serious AEs (any)

event count, event

Secondary/protocol endpoint

Number of Serious Adverse Events (SAEs)

Time frame:Randomisation (week 20) to week 75

Serious AEs (any)

event count, event

Secondary/protocol endpoint

Change in Amylase

Time frame:Run-in (week) 0 to randomization (week 20)

ratio, descriptive

Secondary/protocol endpoint

Change in Amylase

Time frame:Randomisation (week 20) to week 68

ratio, descriptive

Secondary/protocol endpoint

Change in Lipase

Time frame:Run-in (week 0) to randomization (week 20)

ratio, descriptive

Secondary/protocol endpoint

Change in Lipase

Time frame:Randomisation (week 20) to week 68

ratio, descriptive

Secondary/protocol endpoint

Change in Calcitonin

Time frame:Run-in (week 0) to randomization (week 20)

Thyroid event

ratio, event

Secondary/protocol endpoint

Change in Calcitonin

Time frame:Randomisation (week 20) to week 68

Thyroid event

ratio, event

Publications (6)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity.
Obesity (Silver Spring, Md.)2023 Sep (month)PMID37605636doi:10.1002/oby.23842via clinicaltrials gov reference derived + pubmed nct search
Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses.
Diabetes, obesity & metabolism2023 Feb (month)PMID36200477doi:10.1111/dom.14890via clinicaltrials gov reference derived + pubmed nct search
Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program.
Diabetes care2022 Oct 1PMID35724304doi:10.2337/dc21-1785via clinicaltrials gov reference derived + pubmed nct search
Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.
JAMA2021 Apr 13PMID33755728doi:10.1001/jama.2021.3224via CT.gov reference + pubmed nct search
Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5.
Obesity (Silver Spring, Md.)2020 Jun (month)PMID32441473doi:10.1002/oby.22794via CT.gov background + pubmed nct search
Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial.
Lancet (London, England)2018 Aug 25PMID30122305doi:10.1016/S0140-6736(18)31773-2via clinicaltrials gov reference derived + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.