← Trials/Trial dossier/NCT03548935

STEP 1

CompletedPhase 3Results posted

STEP 1: 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

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Subcutaneous · GLP-1 agonist

Listed sites

128

Recruiting sites

—

Enrollment

1,961

actual

Study population

Obesity / overweight

Key I/E criterion

•BMI ≥30

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 IDNCT03548935

Org study IDNN9536-4373

Secondary ID2017-003436-36European Medicines Agency (EudraCT)

Secondary IDU1111-1200-8053World Health Organization (WHO)

Timeline

Milestones

Study start2018-06-04actual

Study first posted2018-06-07actual

Primary completion2020-03-30actual

Study completion2021-03-05actual

Results first posted2021-08-11actual

Last update posted2021-11-19actual

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

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

Endpoints (84)

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

32 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 point	95% CI
Semaglutide 2.4 mgIn-trial observation period	-15.6	—
On-treatment observation period	-16.9	—
PlaceboIn-trial observation period	-2.8	—
On-treatment observation period	-3.1	—

Treatment difference-12.4495% CI-13.37 – -11.51p<.0001ANCOVA

Treatment policy estimand

Treatment difference-14.4295% CI-15.29 – -13.55p<0.0001ANCOVA

Hypothetical estimand

Primary/registry result

Participants Who Achieve 5 or More Percent Body Weight Reduction (Yes/no)

Time frame:After week 68

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgIn-trial observation period	1047	—
In-trial observation period	165	—
On-treatment observation period	978	—
On-treatment observation period	81	—
PlaceboIn-trial observation period	182	—
In-trial observation period	395	—
On-treatment observation period	165	—
On-treatment observation period	334	—

Odds Ratio (OR)11.2295% CI8.88 – 14.19p<0.0001Regression, Logistic

Treatment policy estimand

Odds Ratio (OR)37.0395% CI28.02 – 48.95p<0.0001Regression, Logistic

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 5 or More Percent Body Weight Reduction (Yes/no)

Time frame:After week 68

≥5% weight-loss responders

threshold achievement, improvement

Secondary/registry result

Subjects Who Achieve 10 or More Percent Body Weight Reduction (Yes/no)

Time frame:Week 68

≥10% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	838	—
No	374	—
PlaceboYes	69	—
No	508	—

Secondary/registry result

Participants Who Achieve 15 or More Percent Body Weight Reduction (Yes/no)

Time frame:Week 68

≥15% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	612	—
No	600	—
PlaceboYes	28	—
No	549	—

Secondary/registry result

Participants Who Achieve 20 or More Percent Body Weight Reduction (Yes/no)

Time frame:Week 68

≥20% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes	388	—
No	824	—
PlaceboYes	10	—
No	567	—

Secondary/registry result

Change in Waist Circumference (cm)

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	-14.1	—
Placebo	-4.4	—

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	-16.1	—
Placebo	-2.9	—

Secondary/registry result

Change in Body Mass Index (BMI) (kg/m2)

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	-5.8	—
Placebo	-1.0	—

Secondary/registry result

Change in Body Composition (Total Fat Mass) (%)

Time frame:Baseline (week 0) to week 68

Total fat mass

change from baseline, improvement

Posted result

Group	Value (mean), Percentage point	95% CI
Semaglutide 2.4 mg	-3.9	—
Placebo	-0.3	—

Secondary/registry result

Change in Body Composition (Total Fat Mass) (kg)

Time frame:Baseline (week 0) to week 68

Total fat mass

change from baseline, improvement

Posted result

Group	Value (mean), Kilograms	95% CI
Semaglutide 2.4 mg	-9.3	—
Placebo	-1.5	—

Secondary/registry result

Change in Body Composition (Lean Body Mass) (%)

Time frame:Baseline (week 0) to week 68

Lean mass

change from baseline, improvement

Posted result

Group	Value (mean), Percentage point	95% CI
Semaglutide 2.4 mg	3.4	—
Placebo	0.2	—

Secondary/registry result

Change in Body Composition (Lean Body Mass) (kg)

Time frame:Baseline (week 0) to week 68

Lean mass

change from baseline, improvement

Posted result

Group	Value (mean), Kilograms	95% CI
Semaglutide 2.4 mg	-5.8	—
Placebo	-1.8	—

Secondary/registry result

Change in Body Composition (Visceral Fat Mass) (%)

Time frame:Baseline (week 0) to week 68

Visceral fat, change

change from baseline, improvement

Posted result

Group	Value (mean), Percentage point	95% CI
Semaglutide 2.4 mg	-2.2	—
Placebo	-0.1	—

Secondary/registry result

Change in Body Composition (Visceral Fat Mass) (kg)

Time frame:Baseline (week 0) to week 68

Visceral fat, change

change from baseline, improvement

Posted result

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

Secondary/registry result

Change in Body Weight (%) - DEXA Subpopulation

Time frame:Baseline (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	-15.8	—
Placebo	-3.4	—

Secondary/registry result

Change in Body Weight (kg) - DEXA Subpopulation

Time frame:Baseline (week 0) to week 68

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (mean), Kilograms	95% CI
Semaglutide 2.4 mg	-15.5	—
Placebo	-3.2	—

Secondary/protocol endpoint

Subjects Who Achieve 10 or More Percent Body Weight Reduction (Yes/no)

Time frame:Week 68

≥10% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Participants Who Achieve 15 or More Percent Body Weight Reduction (Yes/no)

Time frame:Week 68

≥15% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Participants Who Achieve 20 or More Percent Body Weight Reduction (Yes/no)

Time frame:Week 68

≥20% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Change in Waist Circumference (cm)

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 (BMI) (kg/m2)

Time frame:Baseline (week 0) to week 68

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Composition (Total Fat Mass) (%)

Time frame:Baseline (week 0) to week 68

Total fat mass

percent change from baseline, improvement

Secondary/protocol endpoint

Change in Body Composition (Total Fat Mass) (kg)

Time frame:Baseline (week 0) to week 68

Total fat mass

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Composition (Lean Body Mass) (%)

Time frame:Baseline (week 0) to week 68

Lean mass

percent change from baseline, improvement

Secondary/protocol endpoint

Change in Body Composition (Lean Body Mass) (kg)

Time frame:Baseline (week 0) to week 68

Lean mass

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Composition (Visceral Fat Mass) (%)

Time frame:Baseline (week 0) to week 68

Visceral fat, change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in Body Composition (Visceral Fat Mass) (kg)

Time frame:Baseline (week 0) to week 68

Visceral fat, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight (%) - DEXA Subpopulation

Time frame:Baseline (week 0) to week 68

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight (kg) - DEXA Subpopulation

Time frame:Baseline (week 0) to week 68

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	-0.2	—

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), millimoles per mole (mmol/mol)	95% CI
Semaglutide 2.4 mg	-5.1	—
Placebo	-1.8	—

Secondary/registry result

Change in Fasting Plasma Glucose (FPG) (mg/dL)

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	-9.2	—
Placebo	-0.4	—

Secondary/registry result

Change in Fasting Serum Insulin (mIU/L) - Ratio to Baseline

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	0.73	—
Placebo	0.92	—

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 (FPG) (mg/dL)

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 (mIU/L) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

ratio, improvement

Cardiometabolic biomarkers

26 endpoints

Secondary/registry result

Change in Systolic Blood Pressure (mmHg)

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	-7	—
Placebo	-1	—

Secondary/registry result

Change in Diastolic Blood Pressure (mmHg)

Time frame:Baseline (week 0) to week 68

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Posted result

Group	Value (mean), Millimeters of mercury (mmHg)	95% CI
Semaglutide 2.4 mg	-3	—
Placebo	-1	—

Secondary/registry result

Change in Total Cholesterol (mg/dL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Posted result

Group	Value (geometric_mean), Ratio of total cholesterol	95% CI
Semaglutide 2.4 mg	0.96	—
Placebo	1.00	—

Secondary/registry result

Change in High-density Lipoproteins (HDL) (mg/dL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

HDL-C, change

ratio, improvement

LOINC 2085-9

Posted result

Group	Value (geometric_mean), Ratio of HDL cholesterol	95% CI
Semaglutide 2.4 mg	1.05	—
Placebo	1.02	—

Secondary/registry result

Change in Low-density Lipoproteins (LDL) (mg/dL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

LDL-C, change

ratio, improvement

LOINC 13457-7

Posted result

Group	Value (geometric_mean), Ratio of LDL cholesterol	95% CI
Semaglutide 2.4 mg	0.97	—
Placebo	1.01	—

Secondary/registry result

Change in Very Low-density Lipoproteins (VLDL) (mg/dL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

VLDL, change

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of VLDL cholesterol	95% CI
Semaglutide 2.4 mg	0.77	—
Placebo	0.92	—

Secondary/registry result

Change in Free Fatty Acids (mg/dL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

Free fatty acids, change

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of free fatty acids	95% CI
Semaglutide 2.4 mg	0.83	—
Placebo	0.93	—

Secondary/registry result

Change in Triglycerides (mg/dL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

Triglycerides, change

ratio, improvement

LOINC 2571-8

Posted result

Group	Value (geometric_mean), Ratio of triglycerides	95% CI
Semaglutide 2.4 mg	0.77	—
Placebo	0.92	—

Secondary/registry result

Change in High Sensitivity C-Reactive Protein (hsCRP) - (mg/L) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

hs-CRP, change

ratio, improvement

LOINC 30522-7

Posted result

Group	Value (geometric_mean), Ratio of hsCRP	95% CI
Semaglutide 2.4 mg	0.45	—
Placebo	0.84	—

Secondary/registry result

Change in Plasminogen Activator Inhibitor-1 (PAI-1) Activity (AU/ml) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of PAI-1	95% CI
Semaglutide 2.4 mg	1.15	—
Placebo	1.53	—

Secondary/registry result

Change in Soluble Leptin Receptor (ng/mL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of soluble leptin receptor	95% CI
Semaglutide 2.4 mg	1.07	—
Placebo	1.02	—

Secondary/registry result

Change in Leptin (ng/mL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

Leptin, change

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of leptin	95% CI
Semaglutide 2.4 mg	0.52	—
Placebo	0.87	—

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	-1	—

Secondary/protocol endpoint

Change in Systolic Blood Pressure (mmHg)

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 (mmHg)

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 (mg/dL) - Ratio to Baseline

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) (mg/dL) - Ratio to Baseline

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) (mg/dL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in Very Low-density Lipoproteins (VLDL) (mg/dL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

VLDL, change

ratio, improvement

Secondary/protocol endpoint

Change in Free Fatty Acids (mg/dL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

Free fatty acids, change

ratio, improvement

Secondary/protocol endpoint

Change in Triglycerides (mg/dL) - Ratio to Baseline

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 (hsCRP) - (mg/L) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

hs-CRP, change

ratio, improvement

LOINC 30522-7

Secondary/protocol endpoint

Change in Plasminogen Activator Inhibitor-1 (PAI-1) Activity (AU/ml) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

ratio, improvement

Secondary/protocol endpoint

Change in Soluble Leptin Receptor (ng/mL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

ratio, improvement

Secondary/protocol endpoint

Change in Leptin (ng/mL) - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

Leptin, change

ratio, improvement

Secondary/protocol endpoint

Change in Pulse

Time frame:Baseline (week 0) to week 68

Heart rate, change

change from baseline, improvement

Patient-reported / QoL

8 endpoints

Secondary/registry result

Change in Short Form 36 (SF-36)

Time frame:Baseline (week 0) to week 68

SF-36 total

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)	2.3	—
Change in SF-36 (role-physical score)	1.1	—
Change in SF-36 (bodily pain score)	0.5	—
Change in SF-36 (general health score)	2.0	—
Change in SF-36 (vitality score)	0.7	—
Change in SF-36 (social functioning score)	-0.3	—
Change in SF-36 (role-emotional score)	-0.9	—
Change in SF-36 (mental health score)	-0.8	—
Change in SF-36 (physical component summary)	2.4	—
Change in SF-36 (mental component summary)	-1.5	—
PlaceboChange in physical functioning score (SF-36)	0.4	—
Change in SF-36 (role-physical score)	-0.2	—
Change in SF-36 (bodily pain score)	-1.3	—
Change in SF-36 (general health score)	-0.6	—
Change in SF-36 (vitality score)	-1.3	—
Change in SF-36 (social functioning score)	-1.4	—
Change in SF-36 (role-emotional score)	-1.5	—
Change in SF-36 (mental health score)	-1.7	—
Change in SF-36 (physical component summary)	0.2	—
Change in SF-36 (mental component summary)	-2.1	—

Secondary/registry result

Change in Impact of Weight on Quality of Life-Lite for Clinical Trial (IWQoL-Lite for CT) Score

Time frame:Baseline (week 0) to week 68

IWQOL-Lite total

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Semaglutide 2.4 mgChange in physical function domain score	15.0	—
Change in physical domain score	14.0	—
Change in psychosocial domain score	17.4	—
Change in total score	16.2	—
PlaceboChange in physical function domain score	6.0	—
Change in physical domain score	5.0	—
Change in psychosocial domain score	6.9	—
Change in total score	6.3	—

Secondary/registry result

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

Time frame:After week 68

SF-36 physical

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes (with threshold 4.3)	318	—
No (with threshold 4.3)	877	—
Yes (with threshold 3.7)	478	—
No (with threshold 3.7)	717	—
PlaceboYes (with threshold 4.3)	97	—
No (with threshold 4.3)	469	—
Yes (with threshold 3.7)	153	—
No (with threshold 3.7)	413	—

Secondary/registry result

Participants Who Achieve "Responder Definition Value" (Yes/no) for IWQoL-Lite for CT Physical Function Domain (5-items) Score

Time frame:After week 68

IWQOL-Lite physical

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Semaglutide 2.4 mgYes (with threshold 20)	473	—
No (with threshold 20)	720	—
Yes (with threshold 14.6)	611	—
No (with threshold 14.6)	582	—
PlaceboYes (with threshold 20)	145	—
No (with threshold 20)	421	—
Yes (with threshold 14.6)	186	—
No (with threshold 14.6)	380	—

Secondary/protocol endpoint

Change in Short Form 36 (SF-36)

Time frame:Baseline (week 0) to week 68

SF-36 total

change from baseline, improvement

Secondary/protocol endpoint

Change in Impact of Weight on Quality of Life-Lite for Clinical Trial (IWQoL-Lite for CT) Score

Time frame:Baseline (week 0) to week 68

IWQOL-Lite total

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:After week 68

SF-36 physical

threshold achievement, improvement

Secondary/protocol endpoint

Participants Who Achieve "Responder Definition Value" (Yes/no) for IWQoL-Lite for CT Physical Function Domain (5-items) Score

Time frame:After week 68

IWQOL-Lite physical

threshold achievement, improvement

Safety / tolerability / PK

10 endpoints

Secondary/registry result

Number of Treatment Emergent Adverse Events (TEAEs)

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	9658	—
Placebo	3302	—

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	164	—
Placebo	53	—

Secondary/registry result

Change in Amylase - Ratio to Baseline

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	1.14	—
Placebo	1.03	—

Secondary/registry result

Change in Lipase - Ratio to Baseline

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	1.41	—
Placebo	0.97	—

Secondary/registry result

Change in Calcitonin - Ratio to Baseline

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	0.99	—
Placebo	0.95	—

Secondary/protocol endpoint

Number of Treatment Emergent Adverse Events (TEAEs)

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 - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

ratio, descriptive

Secondary/protocol endpoint

Change in Lipase - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

ratio, descriptive

Secondary/protocol endpoint

Change in Calcitonin - Ratio to Baseline

Time frame:Baseline (week 0) to week 68

Thyroid event

ratio, event

Publications (12)

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

Proteomic signatures reflect effects of semaglutide treatment for MASH.
JHEP reports : innovation in hepatology2025 Oct (month)PMID40980163doi:10.1016/j.jhepr.2025.101521via clinicaltrials gov reference derived + pubmed nct search
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
The Correlation Between Body Mass Index and Health-Related Quality of Life: Data from Two Weight Loss Intervention Studies.
Advances in therapy2024 Nov (month)PMID39316288doi:10.1007/s12325-024-02932-8via 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
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 Apr (month)PMID36876594doi:10.1002/oby.23732via 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
Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.
Diabetes, obesity & metabolism2022 Aug (month)PMID35441470doi:10.1111/dom.14725via clinicaltrials gov reference derived + pubmed nct search
Confirmatory psychometric evaluations of the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT).
Clinical obesity2021 Oct (month)PMID34296522doi:10.1111/cob.12477via pubmed nct search
Once-Weekly Semaglutide in Adults with Overweight or Obesity.
The New England journal of medicine2021 Mar 18PMID33567185doi:10.1056/NEJMoa2032183via 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.