OverweightPhase 3STEP 5NCT03693430
Two-year Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity
A Phase 3 study testing Semaglutide in people with Overweight and Obesity, run by Novo Nordisk A/S at 41 sites in 5 countries.
Trial summary
This study will look at the change in body weight from the start to the end of the study. Researchers will compare the weight loss in people taking semaglutide (a new medicine) to people taking "dummy" medicine. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Overweight, Obesity
- What is being tested?
- Semaglutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 304 participants
- Where
- 41 sitesin 5 countries
- Study dates
- 5 Oct 2018to 23 Mar 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female, age more than or equal to 18 years at the time of signing informed consent
- Body mass index (BMI) 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
Who cannot join
- HbA1c 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
Trial locations and contacts
41 sites in 5 countries.
41 sites in 5 countries
United States15 sites
Novo Nordisk Investigational Site
Albany, New York, 12203
Novo Nordisk Investigational Site
Arlington, Virginia, 22206
Novo Nordisk Investigational Site
Aurora, Colorado, 80045
Novo Nordisk Investigational Site
Austin, Texas, 78731
Novo Nordisk Investigational Site
Birmingham, Alabama, 35222
Novo Nordisk Investigational Site
Butte, Montana, 59701
Novo Nordisk Investigational Site
City of Saint Peters, Missouri, 63303
Novo Nordisk Investigational Site
Golden, Colorado, 80401
Novo Nordisk Investigational Site
Jacksonville, Florida, 32205
Novo Nordisk Investigational Site
Kingsport, Tennessee, 37660
Novo Nordisk Investigational Site
Los Angeles, California, 90057
Novo Nordisk Investigational Site
Ocala, Florida, 34471
Novo Nordisk Investigational Site
Rochester, New York, 14609
Novo Nordisk Investigational Site
Round Rock, Texas, 78681
Novo Nordisk Investigational Site
Waterbury, Connecticut, 06708
Canada9 sites
Novo Nordisk Investigational Site
Halifax, Nova Scotia, B3H 1V7
Novo Nordisk Investigational Site
Hamilton, Ontario, L8L 5G8
Novo Nordisk Investigational Site
Hamilton, Ontario, L8M 1K7
Novo Nordisk Investigational Site
Moncton, New Brunswick, E1G 1A7
Novo Nordisk Investigational Site
Montreal, Quebec, H4N 2W2
Novo Nordisk Investigational Site
Québec, G1V 4G2
Novo Nordisk Investigational Site
Surrey, British Columbia, V3Z 2N6
Novo Nordisk Investigational Site
Toronto, Ontario, M4G 3E8
Novo Nordisk Investigational Site
Toronto, Ontario, M4P 1P2
Hungary6 sites
Novo Nordisk Investigational Site
Budapest, 1132
Novo Nordisk Investigational Site
Budapest, 1152
Novo Nordisk Investigational Site
Budapest, H-1134
Novo Nordisk Investigational Site
Debrecen, 4043
Novo Nordisk Investigational Site
Komárom, 2900
Novo Nordisk Investigational Site
Szekszárd, 7100
Spain6 sites
Novo Nordisk Investigational Site
Alcorcón, 28922
Novo Nordisk Investigational Site
Almería, 04009
Novo Nordisk Investigational Site
L'Hospitalet de Llobregat, 08907
Novo Nordisk Investigational Site
Pamplona, 31008
Novo Nordisk Investigational Site
Pozuelo de Alarcón, 28223
Novo Nordisk Investigational Site
Seville, 41010
Italy5 sites
Novo Nordisk Investigational Site
Bologna, 40138
Novo Nordisk Investigational Site
Palermo, 90127
Novo Nordisk Investigational Site
Pisa, 56124
Novo Nordisk Investigational Site
Rome, 00168
Novo Nordisk Investigational Site
Siena, 53100
About this study
Official title: Two-year Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity
This study will look at the change in body weight from the start to the end of the study. Researchers will compare the weight loss in people taking semaglutide (a new medicine) to people taking "dummy" medicine. In addition to taking the medicine, participants will also have talks with study staff about healthy food choices, how the participant can be more physically active and what participants can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment the participant gets 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 will last for about 2 years. The participants will have 19 clinic visits and 15 phone calls with the study doctor.
- Conditions
- Overweight, Obesity
- Being tested
- Semaglutide, Placebo (Semaglutide)
- Medical subject headings
- Overweight, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SemaglutideDrug
Subcutaneous (s.c., under the skin) injections of semaglutide once weekly at escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks
Placebo (Semaglutide)Drug
S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Semaglutide | Experimental | Participants will receive semaglutide 2.4 mg during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity. Receives: Drug: Semaglutide |
| Placebo | Placebo comparator | Participants will receive placebo (semaglutide) during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity. Receives: Drug: Placebo (Semaglutide) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change From Baseline (Week 0) to Week 104 in Body Weight
Percentage change in body weight for both in-trial and on-treatment observation period from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Measured: From Baseline (Week 0) to Week 104
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5%
Number of participants who achieved greater than or equal to (>=) 5% weight loss at 104 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 outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Measured: At Week 104
Secondary outcomes (35)
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%
Number of participants who achieved >=10% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: At Week 104
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%
Number of participants who achieved >=15% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: At Week 104
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%
Number of participants who achieved >=20% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: At Week 104
Change From Baseline (Week 0) to Week 104 in Waist Circumference
Change in waist circumference from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Body Weight (kg)
Change in body weight from baseline (week 0) to week 104 in kilogram (kg) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Body Mass Index (BMI)
Change in BMI from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Systolic Blood Pressure
Change in systolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Diastolic Blood Pressure
Change in diastolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change in Total Cholesterol-ratio to Baseline
Change in total cholesterol from baseline (week 0) to week 104 measured in milligrams per deciliter (mg/dL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change in High Density Lipoprotein (HDL) Cholesterol-ratio to Baseline
Change in HDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change in Low Density Lipoprotein (LDL) Cholesterol-ratio to Baseline
Change in LDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change in Very Low Density Lipoprotein (VLDL) Cholesterol-ratio to Baseline
Change in VLDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change in Free Fatty Acids-ratio to Baseline
Change in free fatty acids from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change in Triglycerides-ratio to Baseline
Change in triglycerides from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline
Change in hsCRP from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change in Glycated Haemoglobin (HbA1c) (Percent [%])
Change in HbA1c from baseline (week 0) to week 104 in % is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in HbA1c (mmol/Mol)
Change in HbA1c from baseline (week 0) to week 104 in millimole per mole (mmol/mol) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Fasting Plasma Glucose (FPG) (mmol/L)
Change in FPG from baseline (week 0) to week 104 in millimoles per liter (mmol/L) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in FPG (mg/dL)
Change in FPG from baseline (week 0) to week 104 in mg/dL is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change in Fasting Serum Insulin-ratio to Baseline (Pmol/L)
Change in fasting serum insulin from baseline (week 0) to week 104 measured in picomole per liter (pmol) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Change in Fasting Serum Insulin-ratio to Baseline (mIU/mL)
Change in fasting serum insulin from baseline (week 0) to week 104 measured in milli-international units per milliliter (mIU/mL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Measured: From Baseline (Week 0) to Week 104
Percentage Change From Baseline (Week 0) to Week 52 in Body Weight
Percentage change in body weight from baseline (week 0) to week 52 is presented.
Measured: From Baseline (Week 0) to Week 52
Change From Baseline (Week 0) to Week 52 in Body Weight (kg)
Change in body weight from baseline (week 0) to week 52 in kg is presented.
Measured: From Baseline (Week 0) to Week 52
Change From Baseline (Week 0) to Week 52 in Body Mass Index (BMI)
Change in BMI from baseline (week 0) to week 52 is presented.
Measured: From Baseline (Week 0) to Week 52
Change From Baseline (Week 0) to Week 52 in Waist Circumference
Change in waist circumference from baseline (week 0) to week 52 is presented.
Measured: From Baseline (Week 0) to Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5%
Number of participants who achieved >=5% weight loss at 52 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.
Measured: At Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%
Number of participants who achieved >=10% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss.
Measured: At Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%
Number of participants who achieved >=15% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss.
Measured: At Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%
Number of participants who achieved >=20% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss.
Measured: At Week 52
Number of Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).
Measured: From Baseline (Week 0) to Week 111
Number of Serious Adverse Events (SAEs)
A SAE was defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. The SAEs occurred from week 0 to week 111 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).
Measured: From Baseline (Week 0) to Week 111
Change From Baseline (Week 0) to Week 104 in Pulse
Change in pulse from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Measured: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Amylase
Change in amylase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Measured: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Lipase
Change in lipase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Measured: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Calcitonin
Change in calcitonin from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Measured: From Baseline (Week 0) to Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2018
- Study start5 Oct 2018
- Primary completion29 Jan 2021
- Study completion23 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for OverweightStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 304 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Reporting Anchor and Disclosure (1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03693430
- Sponsor's protocol ID
- NN9536-4378
- Other IDs
- 2017-003726-32, U1111-1202-1740, 2017
- Acronym
- STEP 5
- Status last verified
- Jul 2023
- First submitted
- 1 Oct 2018
- Last updated
- 6 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Publications
Kushner RF, Calanna S, Davies M, Dicker D, Garvey WT, Goldman B, Lingvay I, Thomsen M, Wadden TA, Wharton S, Wilding JPH, Rubino D. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring). 2020 Jun;28(6):1050-1061. doi: 10.1002/oby.22794.
PubMed 32441473Wharton S, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jodar E, Kandler K, Rigas G, Wadden TA, Garvey WT. Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/obesity: STEP 5. Obesity (Silver Spring). 2023 Mar;31(3):703-715. doi: 10.1002/oby.23673. Epub 2023 Jan 18.
PubMed 36655300Wadden TA, Brown GK, Egebjerg C, Frenkel O, Goldman B, Kushner RF, McGowan B, Overvad M, Fink-Jensen A. 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 Intern Med. 2024 Nov 1;184(11):1290-1300. doi: 10.1001/jamainternmed.2024.4346.
PubMed 39226070Wilkinson L, Holst-Hansen T, Laursen PN, Rinnov AR, Batterham RL, Garvey WT. Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity. Obesity (Silver Spring). 2023 Sep;31(9):2249-2259. doi: 10.1002/oby.23842.
PubMed 37605636Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jodar E, Kandler K, Rigas G, Wadden TA, Wharton S; STEP 5 Study Group. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022 Oct;28(10):2083-2091. doi: 10.1038/s41591-022-02026-4. Epub 2022 Oct 10.
PubMed 36216945
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Two-year Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity
- ClinicalTrials.gov ID
- NCT03693430
- Acronym / sponsor ID
- STEP 5 / NN9536-4378
- Conditions
- Overweight, Obesity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 304 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 5 Oct 2018 (actual)
- Primary completion
- 29 Jan 2021 (actual)
- Study completion
- 23 Mar 2021 (actual)
- First posted
- 3 Oct 2018 (actual)
- Results
- Posted 23 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will look at the change in body weight from the start to the end of the study. Researchers will compare the weight loss in people taking semaglutide (a new medicine) to people taking "dummy" medicine. In addition to taking the medicine, participants will also have talks with study staff about healthy food choices, how the participant can be more physically active and what participants can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment the participant gets 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 will last for about 2 years. The participants will have 19 clinic visits and 15 phone calls with the study doctor.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Semaglutide | Experimental | Drug: SemaglutideParticipants will receive semaglutide 2.4 mg during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity. |
| Placebo | Placebo comparator | Drug: Placebo (Semaglutide)Participants will receive placebo (semaglutide) during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female, age more than or equal to 18 years at the time of signing informed consent
- Body mass index (BMI) 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
Key exclusion criteria (2 listed)
- HbA1c 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SemaglutideSubcutaneous (s.c., under the skin) injections of semaglutide once weekly at escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks | Drug | Semaglutide |
| Placebo (Semaglutide)S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks | Drug | Placebo |
Primary outcome
Percentage Change From Baseline (Week 0) to Week 104 in Body Weight
Time frame: From Baseline (Week 0) to Week 104
Percentage change in body weight for both in-trial and on-treatment observation period from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5%
Time frame: At Week 104
Number of participants who achieved greater than or equal to (>=) 5% weight loss at 104 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 outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
35 secondary outcomes
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%
Time frame: At Week 104
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%
Time frame: At Week 104
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%
Time frame: At Week 104
Change From Baseline (Week 0) to Week 104 in Waist Circumference
Time frame: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Body Weight (kg)
Time frame: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Body Mass Index (BMI)
Time frame: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Systolic Blood Pressure
Time frame: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Diastolic Blood Pressure
Time frame: From Baseline (Week 0) to Week 104
Change in Total Cholesterol-ratio to Baseline
Time frame: From Baseline (Week 0) to Week 104
Change in High Density Lipoprotein (HDL) Cholesterol-ratio to Baseline
Time frame: From Baseline (Week 0) to Week 104
Change in Low Density Lipoprotein (LDL) Cholesterol-ratio to Baseline
Time frame: From Baseline (Week 0) to Week 104
Change in Very Low Density Lipoprotein (VLDL) Cholesterol-ratio to Baseline
Time frame: From Baseline (Week 0) to Week 104
Change in Free Fatty Acids-ratio to Baseline
Time frame: From Baseline (Week 0) to Week 104
Change in Triglycerides-ratio to Baseline
Time frame: From Baseline (Week 0) to Week 104
Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline
Time frame: From Baseline (Week 0) to Week 104
Change in Glycated Haemoglobin (HbA1c) (Percent [%])
Time frame: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in HbA1c (mmol/Mol)
Time frame: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Fasting Plasma Glucose (FPG) (mmol/L)
Time frame: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in FPG (mg/dL)
Time frame: From Baseline (Week 0) to Week 104
Change in Fasting Serum Insulin-ratio to Baseline (Pmol/L)
Time frame: From Baseline (Week 0) to Week 104
Change in Fasting Serum Insulin-ratio to Baseline (mIU/mL)
Time frame: From Baseline (Week 0) to Week 104
Percentage Change From Baseline (Week 0) to Week 52 in Body Weight
Time frame: From Baseline (Week 0) to Week 52
Change From Baseline (Week 0) to Week 52 in Body Weight (kg)
Time frame: From Baseline (Week 0) to Week 52
Change From Baseline (Week 0) to Week 52 in Body Mass Index (BMI)
Time frame: From Baseline (Week 0) to Week 52
Change From Baseline (Week 0) to Week 52 in Waist Circumference
Time frame: From Baseline (Week 0) to Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5%
Time frame: At Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%
Time frame: At Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%
Time frame: At Week 52
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%
Time frame: At Week 52
Number of Treatment-emergent Adverse Events (TEAEs)
Time frame: From Baseline (Week 0) to Week 111
Number of Serious Adverse Events (SAEs)
Time frame: From Baseline (Week 0) to Week 111
Change From Baseline (Week 0) to Week 104 in Pulse
Time frame: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Amylase
Time frame: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Lipase
Time frame: From Baseline (Week 0) to Week 104
Change From Baseline (Week 0) to Week 104 in Calcitonin
Time frame: From Baseline (Week 0) to Week 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32441473Kushner RF, Calanna S, Davies M, Dicker D, Garvey WT, Goldman B, Lingvay I, Thomsen M, Wadden TA, Wharton S, Wilding JPH, Rubino D. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring). 2020 Jun;28(6):1050-1061. doi: 10.1002/oby.22794.
- Background: PubMed 36655300Wharton S, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jodar E, Kandler K, Rigas G, Wadden TA, Garvey WT. Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/obesity: STEP 5. Obesity (Silver Spring). 2023 Mar;31(3):703-715. doi: 10.1002/oby.23673. Epub 2023 Jan 18.
- Derived from this study: PubMed 39226070Wadden TA, Brown GK, Egebjerg C, Frenkel O, Goldman B, Kushner RF, McGowan B, Overvad M, Fink-Jensen A. 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 Intern Med. 2024 Nov 1;184(11):1290-1300. doi: 10.1001/jamainternmed.2024.4346.
- Derived from this study: PubMed 37605636Wilkinson L, Holst-Hansen T, Laursen PN, Rinnov AR, Batterham RL, Garvey WT. Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity. Obesity (Silver Spring). 2023 Sep;31(9):2249-2259. doi: 10.1002/oby.23842.
- Derived from this study: PubMed 36216945Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jodar E, Kandler K, Rigas G, Wadden TA, Wharton S; STEP 5 Study Group. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022 Oct;28(10):2083-2091. doi: 10.1038/s41591-022-02026-4. Epub 2022 Oct 10.
- Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Reporting Anchor and Disclosure (1452) study director
Novo Nordisk A/S
41 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Semaglutide in people with Overweight and Obesity, run by Novo Nordisk A/S at 41 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, Canada, Hungary, Spain, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change From Baseline (Week 0) to Week 104 in Body Weight (time frame: From Baseline (Week 0) to Week 104). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03693430, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2023.