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NCT03611582: STEP 3

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

Completed Phase 3 Results posted Last updated 11 November 2021
What this trial tests

Phase 3 trial testing Semaglutide in Overweight in 611 participants. Completed in 28 April 2020.

Timeline
1 August 2018
Primary endpoint
18 March 2020
28 April 2020

Quick facts

Lead sponsorNovo Nordisk A/S
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment611
Start date1 August 2018
Primary completion18 March 2020
Estimated completion28 April 2020
Sites41 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Novo Nordisk A/S — full company profile →

Who can join

18 and older, any sex, with Overweight or Obesity. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Body Weight (%) Primary · Baseline (week 0) to week 68

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 periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (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. Tem

In-trial observation period
GroupValue95% CI
Semaglutide 2.4 mg-16.5± 10.1
Placebo-5.8± 7.7
On-treatment observation period
GroupValue95% CI
Semaglutide 2.4 mg-17.6± 9.6
Placebo-6.1± 7.6
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% Primary · After 68 weeks

Number of participants who achieved greater than or equal to (≥) 5% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 5% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 5% weight loss. 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 i

In-trial observation period
GroupValue95% CI
Semaglutide 2.4 mg323
Placebo90
Semaglutide 2.4 mg50
Placebo99
On-treatment observation period
GroupValue95% CI
Semaglutide 2.4 mg300
Placebo82
Semaglutide 2.4 mg34
Placebo82
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10% Secondary · After 68 weeks

Number of participants who achieved greater than or equal to (≥) 10% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 10% weight loss whereas 'No' infers number of participants who have not achieved ≥ 10% weight loss. 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).

Yes
GroupValue95% CI
Semaglutide 2.4 mg281
Placebo51
No
GroupValue95% CI
Semaglutide 2.4 mg92
Placebo138
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15% Secondary · After 68 weeks

Number of participants who achieved greater than or equal to (≥) 15% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 15% weight loss whereas 'No' infers number of participants who have not achieved ≥ 15% weight loss. 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).

Yes
GroupValue95% CI
Semaglutide 2.4 mg208
Placebo25
No
GroupValue95% CI
Semaglutide 2.4 mg165
Placebo164
Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20% Secondary · After 68 weeks

Number of participants who achieved greater than or equal to (≥) 20% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 20% weight loss whereas 'No' infers number of participants who have not achieved ≥ 20% weight loss. 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).

Yes
GroupValue95% CI
Semaglutide 2.4 mg133
Placebo7
No
GroupValue95% CI
Semaglutide 2.4 mg240
Placebo182
Change in Waist Circumference Secondary · Baseline (week 0) to week 68

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 randomisation (week 0) to last trial-related subject-site contact (week 75).

GroupValue95% CI
Semaglutide 2.4 mg-15.2± 10.2
Placebo-6.1± 8.6
Change in Systolic Blood Pressure Secondary · Baseline (week 0) to week 68

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 randomisation (week 0) to last trial-related subject-site contact (week 75).

GroupValue95% CI
Semaglutide 2.4 mg-6± 14
Placebo-2± 15
Change in Short Form-36 (SF-36) - Physical Functioning Score Secondary · Baseline (week 0) to week 68

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). The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard devi

Change in physical functioning score (SF-36)
GroupValue95% CI
Semaglutide 2.4 mg2.5± 5.7
Placebo1.7± 5.7
Change in SF-36: Role-Physical score
GroupValue95% CI
Semaglutide 2.4 mg1.6± 6.5
Placebo1.5± 6.7
Change in SF-36: Bodily Pain score
GroupValue95% CI
Semaglutide 2.4 mg1.3± 7.1
Placebo0.6± 8.3
Change in SF-36: General Health score
GroupValue95% CI
Semaglutide 2.4 mg3.4± 6.6
Placebo1.9± 6.4
Change in SF-36: Vitality score
GroupValue95% CI
Semaglutide 2.4 mg2.0± 8.2
Placebo0.9± 7.8
Change in SF-36: Social Functioning score
GroupValue95% CI
Semaglutide 2.4 mg0.1± 6.6
Placebo-1.2± 8.0
Change in SF-36: Mental Health score
GroupValue95% CI
Semaglutide 2.4 mg-0.5± 6.0
Placebo-1.5± 7.1
Change in SF-36: Physical component summary
GroupValue95% CI
Semaglutide 2.4 mg3.2± 6.0
Placebo2.6± 6.5
Change in Body Weight (Kg) Secondary · Baseline (week 0) to week 68

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 randomisation (week 0) to last trial-related subject-site contact (week 75).

GroupValue95% CI
Semaglutide 2.4 mg-17.5± 11.4
Placebo-6.2± 8.6
Change in Body Mass Index Secondary · Baseline (week 0) to week 68

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 randomisation (week 0) to last trial-related subject-site contact (week 75).

GroupValue95% CI
Semaglutide 2.4 mg-6.2± 4.0
Placebo-2.2± 3.1
Change in HbA1c (%) Secondary · Baseline (week 0) to week 68

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 randomisation (week 0) to last trial-related subject-site contact (week 75).

GroupValue95% CI
Semaglutide 2.4 mg-0.5± 0.3
Placebo-0.3± 0.2
Change in HbA1c (mmol/Mol) Secondary · Baseline (week 0) to week 68

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 randomisation (week 0) to last trial-related subject-site contact (week 75).

GroupValue95% CI
Semaglutide 2.4 mg-5.8± 3.1
Placebo-3.1± 2.5

Adverse events — posted to ClinicalTrials.gov

Time frame: week 0 to week 75 Results are based on the SAS which included all participants who received at least one dose of semaglutide or placebo.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Semaglutide 2.4 mg
Serious: 37/407 (9%)
Deaths: 0/407
Placebo
Serious: 6/204 (3%)
Deaths: 0/204

Serious adverse events (46 terms)

ReactionSystemSemaglutide 2.4 mgPlacebo
CholelithiasisHepatobiliary disorders
AppendicitisInfections and infestations
Cholecystitis acuteHepatobiliary disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Cervical spinal stenosisMusculoskeletal and connective tissue disorders
CholecystitisHepatobiliary disorders
Abdominal abscessInfections and infestations
Abdominal painGastrointestinal disorders
AnxietyPsychiatric disorders
Back painMusculoskeletal and connective tissue disorders
Biliary dyskinesiaHepatobiliary disorders
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Castleman's diseaseNeoplasms benign, malignant and unspecified (incl cysts and polyps)
CellulitisInfections and infestations
Cerebral infarctionNervous system disorders
Deep vein thrombosisVascular disorders
Gastroenteritis viralInfections and infestations
Haemorrhoids thrombosedGastrointestinal disorders
Hip fractureInjury, poisoning and procedural complications
HydronephrosisRenal and urinary disorders
HypokalaemiaMetabolism and nutrition disorders
Incarcerated inguinal herniaGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders
Invasive lobular breast carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (27 terms — click to expand)

ReactionSystemSemaglutide 2.4 mgPlacebo
NauseaGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
Abdominal painGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
FatigueGeneral disorders
FlatulenceGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
Gastroenteritis viralInfections and infestations
Urinary tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
SinusitisInfections and infestations
DyspepsiaGastrointestinal disorders
EructationGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
Abdominal pain upperGastrointestinal disorders
GastroenteritisInfections and infestations
InfluenzaInfections and infestations
Gastrooesophageal reflux diseaseGastrointestinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Seasonal allergyImmune system disorders

Most-reported serious reactions: Cholelithiasis, Appendicitis, Cholecystitis acute, Osteoarthritis, Cervical spinal stenosis, Cholecystitis, Abdominal abscess, Abdominal pain.

Data from ClinicalTrials.gov NCT03611582 adverse events section.

Sponsor's own description

This study will look at the change in participant's body weight from the start to the end of the study. This is to compare the effect on body weight in people taking semaglutide (a new medicine) and people taking "dummy" medicine. Together with the medicine, the participant will also be part of an intensive lifestyle program where the participant will have talks with study staff about healthy food choices, what the participant can do to lose weight and be more physically active. The participant will either get semaglutide or "dummy" medicine - which treatment the participant gets is decided by chance. The participant 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. For the first 2 months the participant will be on a low calorie diet. The diet is made up of bars, shakes and 1 low calorie pre-prepared meal for each day. The study will last for about 1.5 years. The participant will have 32 clinic visits with the study doctor.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. 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.
    Wadden TA, Bailey TS, Billings LK, Davies M, et al · · 2021 · cited 711× · PMID 33625476 · DOI 10.1001/jama.2021.1831
  2. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5.
    Kushner RF, Calanna S, Davies M, Dicker D, et al · · 2020 · cited 185× · PMID 32441473 · DOI 10.1002/oby.22794
  3. Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss.
    Wharton S, Calanna S, Davies M, Dicker D, et al · · 2022 · cited 98× · PMID 34514682 · DOI 10.1111/dom.14551
  4. The Related Metabolic Diseases and Treatments of Obesity.
    Yang M, Liu S, Zhang C. · · 2022 · cited 89× · PMID 36141228 · DOI 10.3390/healthcare10091616
  5. Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review.
    Mahapatra MK, Karuppasamy M, Sahoo BM. · · 2022 · cited 84× · PMID 35650449 · DOI 10.1007/s11095-022-03302-1
  6. Use of GLP-1 Receptor Agonists and Occurrence of Thyroid Disorders: a Meta-Analysis of Randomized Controlled Trials.
    Hu W, Song R, Cheng R, Liu C, et al · · 2022 · cited 72× · PMID 35898463 · DOI 10.3389/fendo.2022.927859
  7. 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 HJL, Apperloo E, Davies M, Dicker D, et al · · 2023 · cited 64× · PMID 36801984 · DOI 10.2337/dc22-1889
  8. 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 TA, Brown GK, Egebjerg C, Frenkel O, et al · · 2024 · cited 57× · PMID 39226070 · DOI 10.1001/jamainternmed.2024.4346

Verify or expand the search:

Other trials of Semaglutide

Trials testing the same drug.

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Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03611582.

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