A Research Study to See How Semaglutide Helps People With Excess Weight, Lose Weight (STEP UP)

NCT ID: NCT05646706

Last Updated: 2025-12-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1407 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-04
• Study Completion Date: 2024-11-26

Brief Summary

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.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Semaglutide

Intervention Type: DRUG

Participants will receive once-weekly s.c. injections of semaglutide in escalating doses (0.25 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. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.

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.

Group Type: EXPERIMENTAL

Semaglutide

Intervention Type: DRUG

Participants will receive once-weekly s.c. injections of semaglutide in escalating doses (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg) every fourth week. Treatment was continued on the maintenance dose of 2.4 mg once-weekly for an additional 52 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.

Placebo

Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.

Interventions

Semaglutide

Participants will receive once-weekly s.c. injections of semaglutide in escalating doses (0.25 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. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.

Intervention Type: DRUG

Semaglutide

Participants will receive once-weekly s.c. injections of semaglutide in escalating doses (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg) every fourth week. Treatment was continued on the maintenance dose of 2.4 mg once-weekly for an additional 52 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.

Intervention Type: DRUG

Placebo

Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Transparency (dept. 2834)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

Univ of Alabama Birmingham

Birmingham, Alabama, United States

Chambliss Clinical Trials, LLC

Montgomery, Alabama, United States

Healthscan Clinical Trials,LLC.

Montgomery, Alabama, United States

Diablo Clinical Research, Inc.

Walnut Creek, California, United States

Jacksonville Ctr For Clin Res

Jacksonville, Florida, United States

Florida Inst For Clin Res LLC

Orlando, Florida, United States

Florida Institute For Clinical Research LLC

Orlando, Florida, United States

East West Med Res Inst

Honolulu, Hawaii, United States

Midwest Inst For Clin Res

Indianapolis, Indiana, United States

AMC Community Endocrinology

Albany, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

PharmQuest Life Sciences LLC

Greensboro, North Carolina, United States

Medical University Of South Carolina

Charleston, South Carolina, United States

Amarillo Med Spec LLP

Amarillo, Texas, United States

Elligo Clin Res Centre

Austin, Texas, United States

Velocity Clin Res, Dallas

Dallas, Texas, United States

UT Southwestern Medical Center-CRU

Dallas, Texas, United States

DCOL Ctr for Clin Res

Longview, Texas, United States

Sugar Lakes Family Practice PA

Sugar Land, Texas, United States

National Clin Res Inc.

Richmond, Virginia, United States

Selma Medical Associates

Winchester, Virginia, United States

Medical centre Zdrave 1 OOD

Kozloduy, , Bulgaria

Medical center Hippocrates Lukovit EOOD

Lukovit, , Bulgaria

IPMC - Dr. Elizabeta Dimitrova

Petrich, , Bulgaria

Medical center Smolyan clinical research OOD

Smolyan, , Bulgaria

DCC Ascendent OOD

Sofia, , Bulgaria

SGHAT Dr. Shterev EOOD

Sofia, , Bulgaria

Acibadem City Clinic MHAT Tokuda Department of Endocrinology and Metabolic Diseases

Sofia, , Bulgaria

Medical Centre Medical Arts Medico-dental centre

Sofia, , Bulgaria

Medical Center Medical Plus EOOD

Varna, , Bulgaria

AIPSMC Dr. Evelina Zlatanova EOOD

Varna, , Bulgaria

Ocean West Research Clinic

Surrey, British Columbia, Canada

Nova Scotia Health Authority

Halifax, Nova Scotia, Canada

Nova Scotia Hlth Halifax

Halifax, Nova Scotia, Canada

Premier Clinical Trial Research Network (PCTRN)

Hamilton, Ontario, Canada

Wharton Med Clin Trials

Hamilton, Ontario, Canada

Hamilton Med Res Group

Hamilton, Ontario, Canada

Milestone Research

London, Ontario, Canada

Ordinace praktického lékaře

Benátky Na Jizerou, , Czechia

Edumed Broumov

Broumov, , Czechia

Fakultní nemocnice Královské Vinohrady_Praha 10

Prague, , Czechia

Endocare

Prague, , Czechia

Institut klinické a experimentalni mediciny

Prague, , Czechia

Poliklinika Michnova - Obezitologie

Prague, , Czechia

Fledip s.r.o.

Prague, , Czechia

Medizinisches Versorgungszentrum Am Bahnhof Spandau GbR

Berlin, , Germany

Zentrum fuer klinische Studien Suedbrandenburg GmbH

Elsterwerda, , Germany

InnoDiab Forschung GmbH

Essen, , Germany

Praxis Dr. med. M. Esser

Essen, , Germany

Zentrum für klinische Forschung, Dr. med. Lüdemann

Falkensee, , Germany

MedicalCenter am Clemenshospital - Schwerpunktpraxis für Diabetologie und Ernährungsmedizin

Münster, , Germany

RED-Institut für medizinische Forschung und Fortbildung GmbH

Oldenburg in Holstein, , Germany

Praxis Dr. med. Wenzl-Bauer

Rehlingen-Siersburg, , Germany

Zentrum für klinische Studien Allgäu Oberschwaben

Wangen, , Germany

Forschungszentrum Ruhr KliFoCenter GmbH, Kahrmann

Witten, , Germany

University Hospital of Athens ATTIKON

Athens, Attica, Greece

Gen Hospital of Athens Laiko,1st Dpt. of Propaedeutic Inter

Athens, , Greece

Iatriko Athinon (Athens Medical Canter)

Athens, , Greece

Iatriko Athinon 'Palaiou Falirou'

Athens, , Greece

General Hospital of Lamia

Lamia, , Greece

General Hospital of Thessaloniki 'G. Gennimatas

Thessaloniki, , Greece

AHEPA General University Hospital

Thessaloniki, , Greece

"Ippokrateio" G.H. of Thessaloniki

Thessaloniki, , Greece

"Thermi" Private Hosital

Thessaloniki, , Greece

Lausmed Kft.

Baja, Bács-Kiskun county, Hungary

Belinus Bt.

Debrecen, Hajdú-Bihar, Hungary

Borbánya Praxis E.Ü. Kft.

Nyíregyháza, Szabolcs-Szatmar Varmegye, Hungary

ClinDiab Egészségügyi Szolgáltató és Kereskedelmi Kft.

Budapest, , Hungary

Bajcsy-Zsilinszky Kórház

Budapest, , Hungary

MED-TIMA Kft.

Budapest, , Hungary

Fejér Megyei Szent György Oktatókórház

Székesfehérvár, , Hungary

Falck Norge AS

Hamar, , Norway

Oslo universitetssykehus HF Aker

Oslo, , Norway

Sykehuset i Vestfold HF, Tønsberg

Tønsberg, , Norway

Med. Cent. Diabet. Endo. Metabol. DIAB-ENDO-MET

Krakow, Lesser Poland Voivodeship, Poland

NZOZ Przychodnia Specjalistyczna Medica

Lublin, Lubelski, Poland

NZOZ "CenterMed Lublin" Sp. z o.o.

Lublin, Lublin Voivodeship, Poland

Kresmed Sp. z o. o.

Bialystok, Podlaskie Voivodeship, Poland

Centrum Medyczne Pratia Gdynia

Gdynia, Pomeranian Voivodeship, Poland

Uniwersyteckie Centrum Kliniczne SUM w Katowicach

Katowice, , Poland

NBR Polska Tomasz Klodawski

Warsaw, , Poland

PANSTWOWY INSTYTUT MEDYCZNY MSWiA

Warsaw, , Poland

Unidade Local De Saude De Matosinhos E.P.E.

Senhora Da Hora, Matosinhos, Matosinhos, Portugal

APDP - Associação Protectora dos Diabéticos de Portugal

Lisbon, , Portugal

Unidade Local De Saude De Lisboa Ocidental E.P.E. - Hospital Egas Moniz

Lisbon, , Portugal

Hospital Da Luz S.A.

Lisbon, , Portugal

Unidade Local de Saude de Sao Joao E.P.E

Porto, , Portugal

Hospital Luz Arrabida, S.A.

Vila Nova de Gaia, , Portugal

MUDr. Dagmar Prokesova, Endokrinologicka ambulancia

Bratislava, , Slovakia

MEDIMAD, s.r.o., Endokrinologicka ambulancia

Bratislava, , Slovakia

IN-DIA s.r.o.

Lučenec, , Slovakia

SIN AZUCAR s.r.o.

Malacky, , Slovakia

MED-CENTRUM, s.r.o.

Martin, , Slovakia

SVAJDLEROVA, s.r.o.

Prešov, , Slovakia

MEDIVASA, s.r.o., Angiologicka ambulancia

Žilina, , Slovakia

Dom srdca, s.r.o.

Žilina, , Slovakia

Phoenix Pharma

Port Elizabeth, Eastern Cape, South Africa

Medi-Clinic Bloemfontein

Bloemfontein, Free State, South Africa

Soweto Clinical Trial Centre

Johannesburg, Gauteng, South Africa

Deepak Lakha

Johannesburg, Gauteng, South Africa

Hemant Makan

Johannesburg, Gauteng, South Africa

Wits Bara Clinical Trial Site

Johannesburg, Gauteng, South Africa

Precise Clinical Solutions (Pty) Ltd

Durban, KwaZulu-Natal, South Africa

Dr N.K. Gounden Medical Centre

Durban, KwaZulu-Natal, South Africa

Lenmed Shifa Private Hospital

Durban, KwaZulu-Natal, South Africa

Dr T Padayachee

eMkhomazi, KwaZulu-Natal, South Africa

Countries

United States; Bulgaria; Canada; Czechia; Germany; Greece; Hungary; Norway; Poland; Portugal; Slovakia; South Africa

References

Wharton S, Freitas P, Hjelmesaeth J, Kabisch M, Kandler K, Lingvay I, Quiroga M, Rosenstock J, Garvey WT; STEP UP trial group. Once-weekly semaglutide 7.2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025 Nov;13(11):949-963. doi: 10.1016/S2213-8587(25)00226-8. Epub 2025 Sep 14.

Reference Type: DERIVED

PMID: 40961952 (View on PubMed)

Other Identifiers

U1111-1274-4259

Identifier Type: OTHER

Identifier Source: secondary_id

2022-000790-94

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NN9536-4999

Identifier Type: -

Identifier Source: org_study_id