Phase 3 · Semaglutide

STEP 5 trial results

Two-year Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity

Participants: 304
Status: completed
Completed: 2021-03-23
Sponsor: Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT03693430), updated at source Jul 6, 2023. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What STEP 5 measured first

Percentage Change From Baseline (Week 0) to Week 104 in Body Weightpercentage change · From Baseline (Week 0) to Week 104 · mean

Measure	Semaglutide 2.4 mgn=144	Placebon=128
In-trial observation period	-15.9(12.3)	-1.9(8.9)
On-treatment observation period	-17.3(11.9)	-2.0(8.6)

Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5%Participants · At Week 104 · count of participants

Measure	Semaglutide 2.4 mgn=144	Placebon=128
In-trial observation period: Yes	111	44
In-trial observation period: No	33	84
On-treatment observation period: Yes	110	38
On-treatment observation period: No	22	71

Side effects by arm

Side effects in STEP 5

Percent of participants affected, From Baseline (Week 0) to Week 111. The most common events the registry lists.

Event	Semaglutide 2.4 mg	Placebo
Any serious event	7.9%	11.8%
Nausea	53.3%	21.7%
Diarrhoea	34.9%	23.7%
Constipation	30.9%	11.2%
Vomiting	30.3%	4.6%
Nasopharyngitis	15.8%	15.1%
Upper respiratory tract infection	13.2%	15.1%
Abdominal pain upper	14.5%	6.6%
Abdominal pain	13.2%	2.6%
Dyspepsia	13.2%	4.6%
Flatulence	13.2%	6.6%
Gastroenteritis	13.2%	2.6%
Influenza	13.2%	10.5%
Back pain	9.9%	12.5%
Decreased appetite	11.2%	3.9%
Eructation	11.2%	0.7%
Headache	10.5%	10.5%
Abdominal distension	9.9%	5.9%
COVID-19	9.9%	3.9%
Gastrooesophageal reflux disease	9.9%	3.9%
Arthralgia	9.2%	7.2%
Hypertension	3.9%	9.2%
Dizziness	8.6%	5.3%
Urinary tract infection	7.9%	3.9%
Anxiety	5.3%	7.2%
Fatigue	7.2%	5.3%

Secondary outcomes

What else it measured

Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%Participants · At Week 104 · count of participants

Measure	Semaglutide 2.4 mgn=144	Placebon=128
Yes	89	17
No	55	111

Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%Participants · At Week 104 · count of participants

Measure	Semaglutide 2.4 mgn=144	Placebon=128
Yes	75	9
No	69	119

Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%Participants · At Week 104 · count of participants

Measure	Semaglutide 2.4 mgn=144	Placebon=128
Yes	52	3
No	92	125

Change From Baseline (Week 0) to Week 104 in Waist Circumferencecentimeter (cm) · From Baseline (Week 0) to Week 104 · mean

Semaglutide 2.4 mgn=143	Placebon=126
-15.2(12.4)	-4.3(9.1)

Change From Baseline (Week 0) to Week 104 in Body Weight (kg)kilogram · From Baseline (Week 0) to Week 104 · mean

Semaglutide 2.4 mgn=144	Placebon=128
-16.9(14.0)	-2.1(9.5)

Change From Baseline (Week 0) to Week 104 in Body Mass Index (BMI)kilogram per square meter (kg/m^2) · From Baseline (Week 0) to Week 104 · mean

Semaglutide 2.4 mgn=144	Placebon=128
-6.2(5.3)	-0.7(3.5)

Change From Baseline (Week 0) to Week 104 in Systolic Blood Pressuremillimeter of mercury (mmHg) · From Baseline (Week 0) to Week 104 · mean

Semaglutide 2.4 mgn=142	Placebon=125
-6(13)	-1(15)

Change From Baseline (Week 0) to Week 104 in Diastolic Blood PressuremmHg · From Baseline (Week 0) to Week 104 · mean

Semaglutide 2.4 mgn=142	Placebon=125
-4(10)	-1(9)

Change in Total Cholesterol-ratio to BaselineRatio of total cholesterol · From Baseline (Week 0) to Week 104 · geometric mean

Semaglutide 2.4 mgn=141	Placebon=121
0.96(15.3)	1.02(13.5)

Change in High Density Lipoprotein (HDL) Cholesterol-ratio to BaselineRatio of HDL cholesterol · From Baseline (Week 0) to Week 104 · geometric mean

Semaglutide 2.4 mgn=141	Placebon=120
1.09(19.1)	1.08(15.4)

Change in Low Density Lipoprotein (LDL) Cholesterol-ratio to BaselineRatio of LDL cholesterol · From Baseline (Week 0) to Week 104 · geometric mean

Semaglutide 2.4 mgn=141	Placebon=121
0.93(23.8)	0.99(19.1)

Change in Very Low Density Lipoprotein (VLDL) Cholesterol-ratio to BaselineRatio of VLDL cholesterol · From Baseline (Week 0) to Week 104 · geometric mean

Semaglutide 2.4 mgn=141	Placebon=121
0.79(42.3)	1.03(35.1)

The trial

How STEP 5 was run

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.

Semaglutide: Participants will receive semaglutide 2.4 mg during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity.
Placebo: Participants will receive placebo (semaglutide) during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity.

Who could join the trial

Inclusion Criteria: * 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 Exclusion criteria: * 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

Published papers

Papers from STEP 5

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.