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

NCT05646706 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: NN9536-4999U1111-1274-42592022-000790-94
• Study Type: interventional
• Target: 1,407
• Locations: 12 countries
• Sites: 107

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

Outcome Measures

Primary Outcomes (2)

• Semaglutide 7.2 mg Versus Placebo: Relative Change in Body Weight

  Relative change in body weight from baseline (week 0) to end of treatment (week 72) is presented.

  Baseline (week 0), End of treatment (week 72)

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

  Number of participants who achieve body weight reduction \>=5% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction \>=5% and "no" defines participants who did not achieve body weight reduction \>=5%.

  At week 72

Secondary Outcomes (44)

• Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=10% (Yes/no)

  At week 72

• Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=15% (Yes/no)

  At week 72

• Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=20% (Yes/no)

  At week 72

• Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=25% (Yes/no)

  At week 72

• Semaglutide 7.2 mg Versus Placebo: Change in Waist Circumference

  Baseline (week 0), End of treatment (week 72)

Study Arms (3)

Semaglutide 7.2 mg

EXPERIMENTAL

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.

Drug: Semaglutide

Semaglutide 2.4 mg

EXPERIMENTAL

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.

Drug: Semaglutide

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Placebo 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.

Placebo

Semaglutide 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 7.2 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (107)

Univ of Alabama Birmingham

Birmingham, Alabama, 35294, United States

Location

Chambliss Clinical Trials, LLC

Montgomery, Alabama, 36106, United States

Location

Healthscan Clinical Trials,LLC.

Montgomery, Alabama, 36106, United States

Location

Diablo Clinical Research, Inc.

Walnut Creek, California, 94598, United States

Location

Jacksonville Ctr For Clin Res

Jacksonville, Florida, 32216, United States

Location

Florida Inst For Clin Res LLC

Orlando, Florida, 32825, United States

Location

Florida Institute For Clinical Research LLC

Orlando, Florida, 32825, United States

Location

East West Med Res Inst

Honolulu, Hawaii, 96814, United States

Location

Midwest Inst For Clin Res

Indianapolis, Indiana, 46260, United States

Location

AMC Community Endocrinology

Albany, New York, 12203, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

PharmQuest Life Sciences LLC

Greensboro, North Carolina, 27408, United States

Location

Medical University Of South Carolina

Charleston, South Carolina, 29425, United States

Location

Amarillo Med Spec LLP

Amarillo, Texas, 79106, United States

Location

Elligo Clin Res Centre

Austin, Texas, 78704, United States

Location

Velocity Clin Res, Dallas

Dallas, Texas, 75230, United States

Location

UT Southwestern Medical Center-CRU

Dallas, Texas, 75390, United States

Location

DCOL Ctr for Clin Res

Longview, Texas, 75605, United States

Location

Sugar Lakes Family Practice PA

Sugar Land, Texas, 77479, United States

Location

National Clin Res Inc.

Richmond, Virginia, 23294, United States

Location

Selma Medical Associates

Winchester, Virginia, 22601-3834, United States

Location

Medical centre Zdrave 1 OOD

Kozloduy, 3320, Bulgaria

Location

Medical center Hippocrates Lukovit EOOD

Lukovit, 5770, Bulgaria

Location

IPMC - Dr. Elizabeta Dimitrova

Petrich, 2850, Bulgaria

Location

Medical center Smolyan clinical research OOD

Smolyan, 4700, Bulgaria

Location

DCC Ascendent OOD

Sofia, 1202, Bulgaria

Location

SGHAT Dr. Shterev EOOD

Sofia, 1330, Bulgaria

Location

Acibadem City Clinic UMHAT Tokuda EAD, Endocrinology

Sofia, 1407, Bulgaria

Location

Medical Centre Medical Arts Medico-dental centre

Sofia, 1618, Bulgaria

Location

Medical Center Medical Plus EOOD

Varna, 9000, Bulgaria

Location

AIPSMC Dr. Evelina Zlatanova EOOD

Varna, 9010, Bulgaria

Location

Ocean West Research Clinic

Surrey, British Columbia, V3Z 2N6, Canada

Location

Nova Scotia Health Authority

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Nova Scotia Hlth Halifax

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Premier Clinical Trial Research Network (PCTRN)

Hamilton, Ontario, L8L 5G4, Canada

Location

Wharton Med Clin Trials

Hamilton, Ontario, L8L 5G8, Canada

Location

Wharton Medical Clinic Clinical Trials (Hamilton)

Hamilton, Ontario, L8L 5G8, Canada

Location

Hamilton Med Res Group

Hamilton, Ontario, L8M 1K7, Canada

Location

Milestone Research

London, Ontario, N5W 6A2, Canada

Location

Ordinace praktického lékaře

Benátky Na Jizerou, 29471, Czechia

Location

Edumed Broumov

Broumov, 550 01, Czechia

Location

Fakultní nemocnice Královské Vinohrady_Praha 10

Prague, 10034, Czechia

Location

Endocare

Prague, 140 00, Czechia

Location

Institut klinické a experimentalni mediciny

Prague, 14021, Czechia

Location

Poliklinika Michnova - Obezitologie

Prague, 149 00, Czechia

Location

Fledip s.r.o.

Prague, 160 00, Czechia

Location

Medizinisches Versorgungszentrum Am Bahnhof Spandau GbR

Berlin, 13597, Germany

Location

Zentrum fuer klinische Studien Suedbrandenburg GmbH

Elsterwerda, 04910, Germany

Location

InnoDiab Forschung GmbH

Essen, 45136, Germany

Location

Praxis Dr. med. M. Esser

Essen, 45219, Germany

Location

Zentrum für klinische Forschung, Dr. med. Lüdemann

Falkensee, 14612, Germany

Location

MedicalCenter am Clemenshospital - Schwerpunktpraxis für Diabetologie und Ernährungsmedizin

Münster, 48153, Germany

Location

RED-Institut für medizinische Forschung und Fortbildung GmbH

Oldenburg in Holstein, 23758, Germany

Location

Praxis Dr. med. Wenzl-Bauer

Rehlingen-Siersburg, 66780, Germany

Location

Zentrum für klinische Studien Allgäu Oberschwaben

Wangen, 88239, Germany

Location

Forschungszentrum Ruhr KliFoCenter GmbH, Kahrmann

Witten, 58455, Germany

Location

University Hospital of Athens ATTIKON

Athens, Attica, 12462, Greece

Location

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

Athens, 11527, Greece

Location

Iatriko Athinon (Athens Medical Canter)

Athens, 15125, Greece

Location

Iatriko Athinon 'Palaiou Falirou'

Athens, 17562, Greece

Location

General Hospital of Lamia

Lamia, 35100, Greece

Location

General Hospital of Thessaloniki 'G. Gennimatas

Thessaloniki, 54635, Greece

Location

AHEPA General University Hospital

Thessaloniki, 54636, Greece

Location

"Ippokrateio" G.H. of Thessaloniki

Thessaloniki, 54642, Greece

Location

"Thermi" Private Hosital

Thessaloniki, 57001, Greece

Location

Lausmed Kft.

Baja, Bács-Kiskun county, 6500, Hungary

Location

Belinus Bt.

Debrecen, Hajdú-Bihar, 4025, Hungary

Location

Borbánya Praxis E.Ü. Kft.

Nyíregyháza, Szabolcs-Szatmar Varmegye, 4405, Hungary

Location

ClinDiab Egészségügyi Szolgáltató és Kereskedelmi Kft.

Budapest, 1089, Hungary

Location

Bajcsy-Zsilinszky Kórház

Budapest, 1106, Hungary

Location

MED-TIMA Kft.

Budapest, 1132, Hungary

Location

Fejér Megyei Szent György Oktatókórház

Székesfehérvár, 8000, Hungary

Location

Falck Norge AS

Hamar, 2317, Norway

Location

Oslo universitetssykehus HF Aker

Oslo, 0373, Norway

Location

Sykehuset i Vestfold HF, Tønsberg

Tønsberg, 3116, Norway

Location

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

Krakow, Lesser Poland Voivodeship, 31-261, Poland

Location

NZOZ Przychodnia Specjalistyczna Medica

Lublin, Lubelski, 20-538, Poland

Location

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

Lublin, Lublin Voivodeship, 20-044, Poland

Location

Kresmed Sp. z o. o.

Bialystok, Podlaskie Voivodeship, 15-481, Poland

Location

Centrum Medyczne Pratia Gdynia

Gdynia, Pomeranian Voivodeship, 81-338, Poland

Location

Uniwersyteckie Centrum Kliniczne SUM w Katowicach

Katowice, 40-752, Poland

Location

NBR Polska Tomasz Klodawski

Warsaw, 00-710, Poland

Location

PANSTWOWY INSTYTUT MEDYCZNY MSWiA

Warsaw, 02-507, Poland

Location

ULS De Matosinhos E.P.E.- Hospital Pedro Hispano

Senhora Da Hora, Matosinhos, Matosinhos, 4464-513, Portugal

Location

APDP - Associação Protectora dos Diabéticos de Portugal

Lisbon, 1250-230, Portugal

Location

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

Lisbon, 1349-019, Portugal

Location

Hospital da Luz Lisboa, S.A.

Lisbon, 1500-650, Portugal

Location

ULS De São João, E.P.E. - Hospital de São João

Porto, 4200-319, Portugal

Location

Hospital da Luz Arrabida, S.A.

Vila Nova de Gaia, 4400-346, Portugal

Location

MUDr. Dagmar Prokesova, Endokrinologicka ambulancia

Bratislava, 821 01, Slovakia

Location

MEDIMAD, s.r.o., Endokrinologicka ambulancia

Bratislava, 842 31, Slovakia

Location

IN-DIA s.r.o.

Lučenec, 984 01, Slovakia

Location

SIN AZUCAR s.r.o.

Malacky, 901 01, Slovakia

Location

MED-CENTRUM, s.r.o.

Martin, 036 01, Slovakia

Location

SVAJDLEROVA, s.r.o.

Prešov, 080 01, Slovakia

Location

MEDIVASA, s.r.o., Angiologicka ambulancia

Žilina, 010 01, Slovakia

Location

Dom srdca, s.r.o.

Žilina, 01001, Slovakia

Location

Phoenix Pharma

Port Elizabeth, Eastern Cape, 6001, South Africa

Location

Medi-Clinic Bloemfontein

Bloemfontein, Free State, 9301, South Africa

Location

Soweto Clinical Trial Centre

Johannesburg, Gauteng, 1818, South Africa

Location

Deepak Lakha

Johannesburg, Gauteng, 1820, South Africa

Location

Hemant Makan

Johannesburg, Gauteng, 1827, South Africa

Location

Wits Bara Clinical Trial Site

Johannesburg, Gauteng, 2013, South Africa

Location

Precise Clinical Solutions (Pty) Ltd

Durban, KwaZulu-Natal, 4092, South Africa

Location

Dr N.K. Gounden Medical Centre

Durban, KwaZulu-Natal, 4093, South Africa

Location

Lenmed Shifa Private Hospital

Durban, KwaZulu-Natal, 4901, South Africa

Location

Dr T Padayachee

eMkhomazi, KwaZulu-Natal, 4170, South Africa

Location

Related Publications (1)

• 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.

  PMID: 40961952 DERIVED

MeSH Terms

Conditions

Obesity

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Reporting Office (2834)
• Organization: Novo Nordisk A/S

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2022
• First Posted: December 12, 2022
• Study Start: January 4, 2023
• Primary Completion: October 30, 2024
• Study Completion: November 26, 2024
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (10); PT (6); SL (8); HU (7); CA (8); US (21); CZ (7); PL (8); ZA (10); NO (3); GR (9); BU (10)