STEP 3

CompletedPhase 3Results posted

Research Study to Look at How Well Semaglutide is at Lowering Weight When Taken Together With an Intensive Lifestyle Program

Effect and Safety of Semaglutide 2.4 mg Once-weekly as Adjunct to Intensive Behavioural Therapy in Subjects With Overweight or Obesity

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Subcutaneous · GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

611

actual

Study population

Obesity / overweight

Key I/E criterion

—

Primary endpoints

•Body weight, % change•≥5% weight-loss responders

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 IDNCT03611582

Org study IDNN9536-4375

Secondary IDU1111-1200-8199World Health Organization (WHO)

Timeline

Milestones

Study start2018-08-01actual

Study first posted2018-08-02actual

Primary completion2020-03-18actual

Study completion2020-04-28actual

Results first posted2021-07-09actual

Last update posted2021-11-11actual

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 more than or equal to 18 years at the time of signing informed consent

•Body mass index more than or equal to 30 kg/m^2 or more than or equal to 27 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

•Hemoglobin A1c more than or equal to 48 mmol/mol (6.5%) as measured by the 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 (62)

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

Cardiometabolic biomarkers

Weight & body composition

Safety / tolerability / PK

Glycemic / diabetes

Patient-reported / QoL

Other (unclassified)

Weight & body composition

18 endpoints

Primary/registry result

Change in Body Weight (%)

Time frame:Baseline (week 0) to week 68

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage	95% CI
Semaglutide 2.4 mgIn-trial observation period	-16.5	—
On-treatment observation period	-17.6	—
PlaceboIn-trial observation period	-5.8	—
On-treatment observation period	-6.1	—

Treatment difference-10.2795% CI-11.97 – -8.57p<.0001ANCOVA

Treatment policy estimand

Treatment difference-12.6795% CI-14.34 – -11.00p<0.0001MMRM (mixed model repeated measurement)

Hypothetical estimand

Primary/registry result

Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%

Time frame:After 68 weeks

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgIn-trial observation period	323	—
In-trial observation period	50	—
On-treatment observation period	300	—
On-treatment observation period	34	—
PlaceboIn-trial observation period	90	—
In-trial observation period	99	—
On-treatment observation period	82	—
On-treatment observation period	82	—

Odds Ratio (OR)6.1195% CI4.04 – 9.26p<0.0001Regression, Logistic

Treatment policy estimand

Odds Ratio (OR)11.6795% CI7.64 – 17.81p<0.0001MMRM (mixed model repeated measurement)

Hypothetical estimand

Primary/protocol endpoint

Change in Body Weight (%)

Time frame:Baseline (week 0) to week 68

Body weight, % change

percent change from baseline, improvement

Primary/protocol endpoint

Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%

Time frame:After 68 weeks

≥5% weight-loss responders

threshold achievement, improvement

Secondary/registry result

Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10%

Time frame:After 68 weeks

≥10% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	281	—
No	92	—
PlaceboYes	51	—
No	138	—

Secondary/registry result

Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15%

Time frame:After 68 weeks

≥15% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	208	—
No	165	—
PlaceboYes	25	—
No	164	—

Secondary/registry result

Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20%

Time frame:After 68 weeks

≥20% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	133	—
No	240	—
PlaceboYes	7	—
No	182	—

Secondary/registry result

Change in Waist Circumference

Time frame:Baseline (week 0) to week 68

Waist circumference, change

change from baseline, improvement

Posted result

Group	Value (mean), Centimeter (cm)	95% CI
Semaglutide 2.4 mg	-15.2	—
Placebo	-6.1	—

Secondary/registry result

Change in Body Weight (Kg)

Time frame:Baseline (week 0) to week 68

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (mean), Kilogram (kg)	95% CI
Semaglutide 2.4 mg	-17.5	—
Placebo	-6.2	—

Secondary/registry result

Change in Body Mass Index

Time frame:Baseline (week 0) 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	-6.2	—
Placebo	-2.2	—

Secondary/registry result

Change in Body Weight

Time frame:Baseline (week 0) to week 8

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage	95% CI
Semaglutide 2.4 mg	-7.8	—
Placebo	-6.0	—

Secondary/protocol endpoint

Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10%

Time frame:After 68 weeks

≥10% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15%

Time frame:After 68 weeks

≥15% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20%

Time frame:After 68 weeks

≥20% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Change in Waist Circumference

Time frame:Baseline (week 0) to week 68

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight (Kg)

Time frame:Baseline (week 0) to week 68

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Mass Index

Time frame:Baseline (week 0) to week 68

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight

Time frame:Baseline (week 0) to week 8

Body weight, absolute change (kg)

change from baseline, improvement

Glycemic / diabetes

8 endpoints

Secondary/registry result

Change in HbA1c (%)

Time frame:Baseline (week 0) 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	-0.5	—
Placebo	-0.3	—

Secondary/registry result

Change in HbA1c (mmol/Mol)

Time frame:Baseline (week 0) 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	-5.8	—
Placebo	-3.1	—

Secondary/registry result

Change in Fasting Plasma Glucose

Time frame:Baseline (week 0) to week 68

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (mean), milligrams per deciliter (mg/dL)	95% CI
Semaglutide 2.4 mg	-7.3	—
Placebo	-1.1	—

Secondary/registry result

Change in Fasting Serum Insulin

Time frame:Baseline (week 0) to week 68

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of fasting serum insulin	95% CI
Semaglutide 2.4 mg	0.68	—
Placebo	0.84	—

Secondary/protocol endpoint

Change in HbA1c (%)

Time frame:Baseline (week 0) to week 68

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in HbA1c (mmol/Mol)

Time frame:Baseline (week 0) to week 68

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in Fasting Plasma Glucose

Time frame:Baseline (week 0) to week 68

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in Fasting Serum Insulin

Time frame:Baseline (week 0) to week 68

ratio, improvement

Cardiometabolic biomarkers

21 endpoints

Secondary/registry result

Change in Systolic Blood Pressure

Time frame:Baseline (week 0) 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	-6	—
Placebo	-2	—

Secondary/registry result

Change in Diastolic Blood Pressure

Time frame:Baseline (week 0) 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	-3	—
Placebo	-1	—

Secondary/registry result

Change in Total Cholesterol

Time frame:Baseline (week 0) 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	0.96	—
Placebo	1.01	—

Secondary/registry result

Change in High-density Lipoproteins (HDL)

Time frame:Baseline (week 0) 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	1.06	—
Placebo	1.05	—

Secondary/registry result

Change in Low-density Lipoproteins (LDL)

Time frame:Baseline (week 0) 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	0.96	—
Placebo	1.01	—

Secondary/registry result

Change in Very Low Density Lipoprotein (VLDL)

Time frame:Baseline (week 0) to week 68

VLDL, change

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of fasting VLDL cholesterol	95% CI
Semaglutide 2.4 mg	0.77	—
Placebo	0.91	—

Secondary/registry result

Change in Free Fatty Acids

Time frame:Baseline (week 0) 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	0.86	—
Placebo	1.08	—

Secondary/registry result

Change in Triglycerides

Time frame:Baseline (week 0) 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	0.77	—
Placebo	0.91	—

Secondary/registry result

Change in High Sensitivity C-reactive Protein

Time frame:Baseline (week 0) to week 68

hs-CRP, change

change from baseline, improvement

LOINC 30522-7

Posted result

Group	Value (geometric_mean), milligrams per litre (mg/L)	95% CI
Semaglutide 2.4 mg	0.40	—
Placebo	0.76	—

Secondary/registry result/low confidence

Change in Plasminogen Activator Inhibitor-1 Activity

Time frame:Baseline (week 0) to week 68

change from baseline, improvement

Posted result

Group	Value (geometric_mean), Arbritary units per milliliter (AU/ml)	95% CI
Semaglutide 2.4 mg	0.92	—
Placebo	1.26	—

Secondary/registry result

Change in Pulse

Time frame:Baseline (week 0) to week 68

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (mean), beats per minute (bpm)	95% CI
Semaglutide 2.4 mg	3	—
Placebo	2	—

Secondary/protocol endpoint

Change in Systolic Blood Pressure

Time frame:Baseline (week 0) to week 68

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Change in Diastolic Blood Pressure

Time frame:Baseline (week 0) to week 68

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Secondary/protocol endpoint

Change in Total Cholesterol

Time frame:Baseline (week 0) to week 68

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Secondary/protocol endpoint

Change in High-density Lipoproteins (HDL)

Time frame:Baseline (week 0) to week 68

HDL-C, change

ratio, improvement

LOINC 2085-9

Secondary/protocol endpoint

Change in Low-density Lipoproteins (LDL)

Time frame:Baseline (week 0) to week 68

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in Very Low Density Lipoprotein (VLDL)

Time frame:Baseline (week 0) to week 68

VLDL, change

ratio, improvement

Secondary/protocol endpoint

Change in Free Fatty Acids

Time frame:Baseline (week 0) to week 68

Free fatty acids, change

ratio, improvement

Secondary/protocol endpoint

Change in Triglycerides

Time frame:Baseline (week 0) to week 68

Triglycerides, change

ratio, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change in High Sensitivity C-reactive Protein

Time frame:Baseline (week 0) to week 68

hs-CRP, change

change from baseline, improvement

LOINC 30522-7

Secondary/protocol endpoint

Change in Pulse

Time frame:Baseline (week 0) to week 68

Heart rate, change

change from baseline, improvement

Patient-reported / QoL

4 endpoints

Secondary/registry result

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

Time frame:Baseline (week 0) to week 68

SF-36 physical

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Semaglutide 2.4 mgChange in physical functioning score (SF-36)	2.5	—
Change in SF-36: Role-Physical score	1.6	—
Change in SF-36: Bodily Pain score	1.3	—
Change in SF-36: General Health score	3.4	—
Change in SF-36: Vitality score	2.0	—
Change in SF-36: Social Functioning score	0.1	—
Change in SF-36: Mental Health score	-0.5	—
Change in SF-36: Physical component summary	3.2	—
Change in SF-36: Mental component summary	-0.9	—
Change in SF-36: Role-Emotional score	-0.6	—
PlaceboChange in physical functioning score (SF-36)	1.7	—
Change in SF-36: Role-Physical score	1.5	—
Change in SF-36: Bodily Pain score	0.6	—
Change in SF-36: General Health score	1.9	—
Change in SF-36: Vitality score	0.9	—
Change in SF-36: Social Functioning score	-1.2	—
Change in SF-36: Mental Health score	-1.5	—
Change in SF-36: Physical component summary	2.6	—
Change in SF-36: Mental component summary	-2.2	—
Change in SF-36: Role-Emotional score	-1.5	—

Secondary/registry result

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

Time frame:After 68 weeks

SF-36 physical

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes (with threshold 4.3)	86	—
No (with threshold 4.3)	278	—
Yes (with threshold 3.7)	133	—
No (with threshold 3.7)	231	—
PlaceboYes (with threshold 4.3)	36	—
No (with threshold 4.3)	145	—
Yes (with threshold 3.7)	51	—
No (with threshold 3.7)	130	—

Secondary/protocol endpoint

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

Time frame:Baseline (week 0) to week 68

SF-36 physical

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:After 68 weeks

SF-36 physical

threshold achievement, improvement

Safety / tolerability / PK

10 endpoints

Secondary/registry result

Number of Treatment-emergent Adverse Events (AEs)

Time frame:Baseline (week 0) to week 75

Treatment-emergent AEs (any)

event count, event

Posted result

Group	Value (number), events	95% CI
Semaglutide 2.4 mg	4035	—
Placebo	1325	—

Secondary/registry result

Number of Serious Adverse Events (SAEs)

Time frame:Baseline (week 0) to week 75

Serious AEs (any)

event count, event

Posted result

Group	Value (number), events	95% CI
Semaglutide 2.4 mg	55	—
Placebo	7	—

Secondary/registry result

Change in Amylase

Time frame:Baseline (week 0) to week 68

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of amylase	95% CI
Semaglutide 2.4 mg	1.12	—
Placebo	1.07	—

Secondary/registry result

Change in Lipase

Time frame:Baseline (week 0) to week 68

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of lipase	95% CI
Semaglutide 2.4 mg	1.31	—
Placebo	0.94	—

Secondary/registry result

Change in Calcitonin

Time frame:Baseline (week 0) to week 68

Thyroid event

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of calcitonin	95% CI
Semaglutide 2.4 mg	0.93	—
Placebo	0.94	—

Secondary/protocol endpoint

Number of Treatment-emergent Adverse Events (AEs)

Time frame:Baseline (week 0) to week 75

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

Number of Serious Adverse Events (SAEs)

Time frame:Baseline (week 0) to week 75

Serious AEs (any)

event count, event

Secondary/protocol endpoint

Change in Amylase

Time frame:Baseline (week 0) to week 68

ratio, descriptive

Secondary/protocol endpoint

Change in Lipase

Time frame:Baseline (week 0) to week 68

ratio, descriptive

Secondary/protocol endpoint

Change in Calcitonin

Time frame:Baseline (week 0) to week 68

Thyroid event

ratio, event

Other (unclassified)

1 endpoint

Secondary/protocol endpoint/low confidence

Change in Plasminogen Activator Inhibitor-1 Activity

Time frame:Baseline (week 0) to week 68

change from baseline, improvement

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

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 medicine2024 Nov 1PMID39226070doi:10.1001/jamainternmed.2024.4346via clinicaltrials gov reference derived + pubmed nct search
Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials.
Diabetes care2023 Apr 1PMID36801984doi:10.2337/dc22-1889via 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 Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial.
JAMA2021 Apr 13PMID33625476doi:10.1001/jama.2021.1831via 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.