Phase 3 · Semaglutide

STEP UP trial results

Effect and Safety of Semaglutide 7.2 mg Once-weekly in Participants With Obesity

Semaglutide 7.2 mg Versus Placebo: Relative Change in Body Weight (Percentage (%) change in body weight), Baseline (week 0), End of treatment (week 72). Semaglutide 7.2 mg: -19.5; Placebo: -3.8.

Participants: 1,407
Status: completed
Completed: 2024-11-26
Sponsor: Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT05646706), updated at source Apr 23, 2026. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What STEP UP measured first

Semaglutide 7.2 mg Versus Placebo: Relative Change in Body WeightPercentage (%) change in body weight · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=950	Placebon=171
-19.5(10.6)	-3.8(7.1)

Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction Greater Than or Equal to (>=) 5% (Yes/no)Participants · At week 72 · count of participants

Measure	Semaglutide 7.2 mgn=950	Placebon=171
Yes	862	63
No	88	108

Side effects by arm

Side effects in STEP UP

Percent of participants affected, From baseline (week 0) to end of study (week 81). The most common events the registry lists.

Event	Semaglutide 7.2 mg	Semaglutide 2.4 mg	Placebo
Any serious event	7.3%	10.9%	5.5%
Nausea	43.7%	38.3%	13.4%
Diarrhoea	27.3%	27.9%	12.9%
Vomiting	24.8%	16.4%	7%
Constipation	23.3%	19.4%	9%
Nasopharyngitis	8.2%	7.5%	12.4%
COVID-19	11.4%	10.4%	11.9%
Fatigue	11.2%	9.5%	3.5%
Dyspepsia	10.3%	6%	3.5%
Headache	9.9%	8%	8.5%
Eructation	9.2%	8%	0.5%
Upper respiratory tract infection	6.1%	6.5%	7.5%
Decreased appetite	7.4%	5%	4.5%
Alopecia	7.2%	4%	1.5%
Sensitive skin	7.1%	0%	0%
Arthralgia	4.3%	7%	4.5%
Back pain	5.1%	7%	2%
Gastrooesophageal reflux disease	4.8%	6.5%	3%
Dizziness	6.3%	6%	1.5%
Abdominal pain	6.2%	6%	3%
Hypertension	1.8%	3.5%	6%
Sinusitis	3.5%	6%	4%
Abdominal pain upper	5.8%	2%	5%
Hyperaesthesia	5.5%	0.5%	0.5%

Secondary outcomes

What else it measured

Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=10% (Yes/no)Participants · At week 72 · count of participants

Measure	Semaglutide 7.2 mgn=950	Placebon=171
Yes	783	35
No	167	136

Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=15% (Yes/no)Participants · At week 72 · count of participants

Measure	Semaglutide 7.2 mgn=950	Placebon=171
Yes	632	13
No	318	158

Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=20% (Yes/no)Participants · At week 72 · count of participants

Measure	Semaglutide 7.2 mgn=950	Placebon=171
Yes	453	5
No	497	166

Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=25% (Yes/no)Participants · At week 72 · count of participants

Measure	Semaglutide 7.2 mgn=950	Placebon=171
Yes	296	0
No	654	171

Semaglutide 7.2 mg Versus Placebo: Change in Waist CircumferenceCentimeter (cm) · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=950	Placebon=171
-18.0(10.5)	-5.6(7.4)

Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Relative Change in Body WeightPercentage (%) change in body weight · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=950	Semaglutide 2.4 mgn=189
-19.5(10.6)	-16.4(9.2)

Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of Participants Who Achieve Body Weight Reduction >=20% (Yes/no)Participants · At week 72 · count of participants

Measure	Semaglutide 7.2 mgn=950	Semaglutide 2.4 mgn=189
Yes	453	63
No	497	126

Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of Participants Who Achieve Body Weight Reduction >=25% (Yes/no)Participants · At week 72 · count of participants

Measure	Semaglutide 7.2 mgn=950	Semaglutide 2.4 mgn=189
Yes	296	29
No	654	160

Semaglutide 7.2 mg Versus Placebo: Change in Body WeightKilograms (kg) · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=950	Placebon=171
-21.7(12.3)	-4.3(8.0)

Semaglutide 7.2 mg Versus Placebo: Change in Body Mass Index (BMI)kilogram per square meter (kg/m^2) · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=950	Placebon=171
-7.7(4.4)	-1.5(2.9)

Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Change in Body WeightKg · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=950	Semaglutide 2.4 mgn=189
-21.7(12.3)	-18.7(10.4)

Pooled Semaglutide Versus Placebo: Change in Total Fat Volume (%)% of total fat volume · Baseline (week 0), End of treatment (week 72) · mean

Pooled Semaglutide (7.2 mg + 2.4 mg)n=45	Placebon=5
-26.9(18.1)	-2.7(7.3)

The trial

How STEP UP was run

This study will look at how much weight participants will lose from the start to the end of the study. The weight loss in participants taking the investigational high dose of semaglutide will be compared to the weight loss in people taking "dummy" medicine and a lower dose of semaglutide. In addition to taking the medicine, participants will have talks with study staff about healthy food choices and how to be more physically active. Participants will either get semaglutide or "dummy" medicine. Which treatment participants get is decided by chance. Participants are more likely (4 out of 5) to get semaglutide than the "dummy" medicine. The study medicine will be injected briefly, under skin, with a thin needle, typically in the stomach, thighs, or upper arms. In the first part of the study, participants will get one injection once a week until they reach the planned dose. The second part of the study, which might last a couple of months, is a transition period, where participant will get three injections, taken right after each other, once a week. The duration of the study intervention (trial product and lifestyle intervention) will be 72 weeks followed by a 9-week follow-up period without study interventions.

Semaglutide 7.2 mg: Participants will receive once-weekly injection of semaglutide subcutaneously (s.c.) in 20 week dose escalation period with dose escalation (0.25 milligram \[mg\], 0.5 mg, 1.0 mg, 1.7 mg, 2.4 mg, and 7.2 mg) every fourth week. Treatment was continued on the maintenance dose of 7.2 mg once-weekly for an additional 52 weeks until week 72.
Semaglutide 2.4 mg: Participants will receive once-weekly s.c. injection of semaglutide in 20 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once-weekly for an additional 52 weeks until week 72.
Placebo: Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks.

Who could join the trial

Inclusion Criteria: * Male or female. * Age above or equal to 18 years at the time of signing informed consent. * Body mass index (BMI) greater than or equal to 30.0 kilogram per square meter (kg/m\^2). * History of at least one self-reported unsuccessful dietary effort to lose body weight. Exclusion Criteria: * HbA1c greater than or equal to 48 millimoles per mole (mmol/mol) (6.5 percent) as measured by the central laboratory at screening. * History of type 1 or type 2 diabetes. * Treatment with glucose-lowering agent(s) within 90 days before screening. * A self-reported change in body weight greater than 5 kilograms (kg) (11 pounds) within 90 days before screening irrespective of medical records. * Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.

Published papers

Papers from STEP UP

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

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