Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

Short name STEP 1

NCTNCT03548935Other idNN9536-4373Other idU1111-1200-8053Other id2017-003436-36Other id2017

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 3
Enrollment: 1,961 participants (actual)
Sponsor: Novo Nordisk A/S · Industry
Design: Randomized · Quadruple masking
Countries: 17 countries
United States, Argentina, Belgium, Bulgaria, Canada, Denmark, Finland, France, Germany, India, Japan, Mexico, Poland, Puerto Rico, Russia, Taiwan, United Kingdom
Start: 4 Jun 2018
Primary completion: 30 Mar 2020
Completion: 5 Mar 2021
First posted: 7 Jun 2018
Last update posted: 19 Nov 2021
Conditions: Metabolism and Nutrition Disorder · Overweight or Obesity

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

20182019202020212022

Ph 3
STEP 1
NCT03548935
4 Jun 2018 to 5 Mar 2021

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

SemaglutideDrug
Placebo (semaglutide)Drug

Arms2

Experimental
Semaglutide s.c. 2.4 mg once weekly
Participants will receive semaglutide for 68 weeks.
Placebo comparator
Semaglutide placebo
Participants will receive semaglutide matching placebo for 68 weeks.

Primary outcomes2

Outcomes the sponsor listed as primary.

Change in Body Weight (%)
Time frame · Baseline (week 0) to week 68
Registry description
Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from date of randomization (week 0) to date of last contact with trial site (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Participants Who Achieve 5 or More Percent Body Weight Reduction (Yes/no)
Time frame · After week 68
Registry description
Number of participants who achieved weight loss more than or equal to 5% (yes/no) at week 68 are presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption.

Secondary outcomes(20)

Subjects Who Achieve 10 or More Percent Body Weight Reduction (Yes/no)
Time frame · Week 68
Registry description
Number of participants who achieved weight loss more than or equal to (≥) 10% at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from date of randomization (week 0) to date of last contact with trial site (week 75).
Participants Who Achieve 15 or More Percent Body Weight Reduction (Yes/no)
Time frame · Week 68
Registry description
Number of participants who achieved more than or equal to (≥) 15% weight loss at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Participants Who Achieve 20 or More Percent Body Weight Reduction (Yes/no)
Time frame · Week 68
Registry description
Number of participants who achieved more than or equal to (≥) 20% weight loss at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in Waist Circumference (cm)
Time frame · Baseline (week 0) to week 68
Registry description
Change in waist circumference from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to date of last contact with trial site (week 75).
Change in Systolic Blood Pressure (mmHg)
Time frame · Baseline (week 0) to week 68
Registry description
Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to date of last contact with trial site (week 75).
Change in Short Form 36 (SF-36)
Time frame · Baseline (week 0) to week 68
Registry description
SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation, respectively, for the 2009 US general population. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
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
Registry description
IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. It is used to assess the impact of body weight changes on patients' physical and psychosocial functioning in three composite scores (physical function, physical and psychosocial) and a total score. The scores range between 0-100 where higher scores indicate a better quality of life. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in Body Weight (kg)
Time frame · Baseline (week 0) to week 68
Registry description
Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in Body Mass Index (BMI) (kg/m2)
Time frame · Baseline (week 0) to week 68
Registry description
Change in body mass index from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in HbA1C (%)
Time frame · Baseline (week 0) to week 68
Registry description
Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in HbA1C (mmol/Mol)
Time frame · Baseline (week 0) to week 68
Registry description
Change in HbA1c from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in Fasting Plasma Glucose (FPG) (mg/dL)
Time frame · Baseline (week 0) to week 68
Registry description
Change in fasting plasma glucose from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in Fasting Serum Insulin (mIU/L) - Ratio to Baseline
Time frame · Baseline (week 0) to week 68
Registry description
Change in fasting serum insulin from week 0 to week 68 is presented as ratio to baseline. Fasting serum insulin was measured in milli-international units per milliliter (mIU/mL). The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in Diastolic Blood Pressure (mmHg)
Time frame · Baseline (week 0) to week 68
Registry description
Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in Total Cholesterol (mg/dL) - Ratio to Baseline
Time frame · Baseline (week 0) to week 68
Registry description
Change in fasting total cholesterol from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in High-density Lipoproteins (HDL) (mg/dL) - Ratio to Baseline
Time frame · Baseline (week 0) to week 68
Registry description
Change in fasting HDL from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in Low-density Lipoproteins (LDL) (mg/dL) - Ratio to Baseline
Time frame · Baseline (week 0) to week 68
Registry description
Change in fasting LDL from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in Very Low-density Lipoproteins (VLDL) (mg/dL) - Ratio to Baseline
Time frame · Baseline (week 0) to week 68
Registry description
Change in fasting VLDL from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in Free Fatty Acids (mg/dL) - Ratio to Baseline
Time frame · Baseline (week 0) to week 68
Registry description
Change in fasting free fatty acids from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Change in Triglycerides (mg/dL) - Ratio to Baseline
Time frame · Baseline (week 0) to week 68
Registry description
Change in fasting triglycerides from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Baseline (week 0) to week 68

Change in Body Weight (%)

Group	Value (Percentage point)	Spread
Semaglutide 2.4 mg	-15.6	10.1
Placebo	-2.8	6.5

Primary outcomeCount of participants· After week 68

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

Group	Value (Participants)
Semaglutide 2.4 mg	1047
Placebo	182

Secondary and other outcome results(6)

Secondary outcomeCount of participants· Week 68

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

Group	Value (Participants)
Semaglutide 2.4 mg	838
Placebo	69

Secondary outcomeCount of participants· Week 68

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

Group	Value (Participants)
Semaglutide 2.4 mg	612
Placebo	28

Secondary outcomeCount of participants· Week 68

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

Group	Value (Participants)
Semaglutide 2.4 mg	388
Placebo	10

Secondary outcomeMean· Baseline (week 0) to week 68

Change in Waist Circumference (cm)

Group	Value (Centimeter (cm))	Spread
Semaglutide 2.4 mg	-14.1	9.6
Placebo	-4.4	6.9

Secondary outcomeMean· Baseline (week 0) to week 68

Change in Systolic Blood Pressure (mmHg)

Group	Value (Millimeters of mercury (mmHg))	Spread
Semaglutide 2.4 mg	-7	14
Placebo	-1	13

Secondary outcomeMean· Baseline (week 0) to week 68

Change in Short Form 36 (SF-36)

Group	Value (Score on a scale)	Spread
Semaglutide 2.4 mg	2.3	6.6
Placebo	0.4	7.4

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Sema 2.4 mgParticipants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	1 / 1306	128 / 1306	1052 / 1306
PlaceboParticipants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	1 / 655	42 / 655	447 / 655

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies11

Studies that cite this trial.

Studies with results

5 studies on this page

Indexing hint: Randomized controlled trial · 2024

5 results

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.

Wadden et al. 2024JAMA internal medicinecited by 77

PMID 39226070PMC11372653DOI 10.1001/jamainternmed.2024.4346PUB-39226070

Free to read · publisher termsCC BY-NC-ND5 results

Read at source See results (5)

Indexing hint: Randomized controlled trial · 2023

4 results

Impact of BMI and comorbidities on efficacy of once-weekly semaglutide: Post hoc analyses of the STEP 1 randomized trial.

McGowan et al. 2023Obesity (Silver Spring, Md.)cited by 13

PMID 36876594DOI 10.1002/oby.23732PUB-36876594

Free to read · publisher termsCC BY-NC4 results

Read at source See results (4)

Indexing hint: Randomized controlled trial · 2022

4 results

Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.

Wilding et al. 2022Diabetes, obesity & metabolismcited by 874

PMID 35441470PMC9542252DOI 10.1111/dom.14725PUB-35441470

CC BY4 results

Download PDF See results (4)

Indexing hint: Randomized controlled trial · 2021

10 results

Once-Weekly Semaglutide in Adults with Overweight or Obesity.

Wilding et al. 2021The New England journal of medicinecited by 3,862

PMID 33567185DOI 10.1056/nejmoa2032183PUB-33567185

Full text at the publisher10 results

Publisher page See results (10)

Indexing hint: Randomized controlled trial · 2020

Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5.

Kushner et al. 2020Obesity (Silver Spring, Md.)cited by 209

PMID 32441473PMC7318657DOI 10.1002/oby.22794PUB-32441473

Free to read · publisher termsCC BY-NC

Read at source

Indexing hint: Randomized controlled trial · 2018

10 results

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.

O'Neil et al. 2018Lancet (London, England)cited by 615

PMID 30122305DOI 10.1016/s0140-6736(18)31773-2PUB-30122305

Full text at the publisher10 results

Publisher page See results (10)

More studies

5 studies on this page

PubMed tag: none · 2025

Proteomic signatures reflect effects of semaglutide treatment for MASH.

Schattenberg et al. 2025JHEP reports : innovation in hepatologycited by 6

PMID 40980163PMC12447996DOI 10.1016/j.jhepr.2025.101521PUB-40980163

CC BY

Download PDF

Indexing hint: Randomized controlled trial · 2024

Corrected

Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: Patient-reported outcomes from the STEP 1-4 trials.

Rubino et al. 2024Diabetes, obesity & metabolismcited by 38

PMID 38698650DOI 10.1111/dom.15620PUB-38698650

Full text at the publisher

Publisher page Read the notice

PubMed tag: none · 2023

Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses.

Kosiborod et al. 2023Diabetes, obesity & metabolismcited by 98

PMID 36200477PMC10092593DOI 10.1111/dom.14890PUB-36200477

Free to read · publisher termsCC BY-NC

Read at source

PubMed tag: none · 2023

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.

Heerspink et al. 2023Diabetes carecited by 74

PMID 36801984PMC10090901DOI 10.2337/dc22-1889PUB-36801984

Rights unknown

Source link

PubMed tag: none · 2022

Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program.

Perreault et al. 2022Diabetes carecited by 61

PMID 35724304PMC9862484DOI 10.2337/dc21-1785PUB-35724304

Rights unknown

Source link

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

DerivedKral P, Holst-Hansen T, Olivieri AV, Ivanescu C, Lamotte M, Larsen S. The Correlation Between Body Mass Index and Health-Related Quality of Life: Data from Two Weight Loss Intervention Studies. Adv Ther. 2024 Nov;41(11):4228-4247. doi: 10.1007/s12325-024-02932-8. Epub 2024 Sep 24. PMID 39316288

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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

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