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

Phase 3

Completed

• Conditions: Obesity
• Interventions: Drug: Placebo; Drug: Semaglutide

• Registration Number: NCT05646706
• Lead Sponsor: Novo Nordisk A/S

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-02
• Study First Submitted QC: 2022-12-02
• Study First Posted: 2022-12-12
• Study Start: 2023-01-04
• Primary Completion: 2024-10-30
• Study Completion: 2024-11-26
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-23
• Last Update Posted: 2025-04-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1407

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks.
Semaglutide 7.2 mg	Semaglutide	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	Semaglutide	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.

Primary Outcome Measures

Name	Time	Method
Semaglutide 7.2 mg versus Placebo: Relative change in body weight	From baseline (week 0) to end of treatment (week 72)	Measured in percentage (%).
Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction greater than or equal to (>=) 5% (yes/no)	From baseline (week 0) to end of treatment (week 72)	Measured as count of participants.

Secondary Outcome Measures

Name	Time	Method
Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction >=10% (yes/no)	From baseline (week 0) to end of treatment (week 72)	Measured as count of participants.
Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Relative change in body weight	From baseline (week 0) to end of treatment (week 72)	Measured in percentage (%).
Semaglutide 7.2 mg versus Placebo: Change in diastolic blood pressure	From baseline (week 0) to end of treatment (week 72)	Measured in mmHg.
Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction >=20% (yes/no)	From baseline (week 0) to end of treatment (week 72)	Measured as count of participants.
Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction >=25% (yes/no)	From baseline (week 0) to end of treatment (week 72)	Measured as count of participants.
Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction >=15% (yes/no)	From baseline (week 0) to end of treatment (week 72)	Measured as count of participants.
Semaglutide 7.2 mg versus Placebo: Change in waist circumference	From baseline (week 0) to end of treatment (week 72)	Measured in centimeters (cm).
Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Number of participants who achieve body weight reduction >=25% (yes/no)	From baseline (week 0) to end of treatment (week 72)	Measured as count of participants.
Semaglutide 7.2 mg versus Placebo: Change in body weight	From baseline (week 0) to end of treatment (week 72)	Measured in kilograms (kg).
Semaglutide 7.2 mg versus Placebo: Change in high-density lipoprotein (HDL) cholesterol	From baseline (week 0) to end of treatment (week 72)	Measured in ratio to baseline.
Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Number of participants who achieve body weight reduction >=20% (yes/no)	From baseline (week 0) to end of treatment (week 72)	Measured as count of participants.
Semaglutide 7.2 mg versus Placebo: Change in body mass index (BMI)	From baseline (week 0) to end of treatment (week 72)	Measured in kilogram per square meter (kg/m\^2).
Semaglutide 7.2 mg versus Placebo: Change in total fat mass (%)	From baseline (week 0) to end of treatment (week 72)	Measured in percentage (%).
Semaglutide 7.2 mg versus Placebo: Change in lean body mass (%)	From baseline (week 0) to end of treatment (week 72)	Measured in percentage (%).
Semaglutide 7.2 mg versus Placebo: Change in visceral fat mass (%)	From baseline (week 0) to end of treatment (week 72)	Measured in percentage (%).
Semaglutide 7.2 mg versus Placebo: Change in low-density lipoprotein (LDL) cholesterol	From baseline (week 0) to end of treatment (week 72)	Measured in ratio to baseline.
Semaglutide 7.2 mg versus Placebo: Change in very low-density lipoprotein (VLDL) cholesterol	From baseline (week 0) to end of treatment (week 72)	Measured in ratio to baseline.
Semaglutide 7.2 mg versus Placebo: Change in total fat mass (liters)	From baseline (week 0) to end of treatment (week 72)	Measured in liters.
Semaglutide 7.2 mg versus Placebo: Change in lean body mass (liters)	From baseline (week 0) to end of treatment (week 72)	Measured in liters.
Semaglutide 7.2 mg versus Placebo: Change in visceral fat mass (liters)	From baseline (week 0) to end of treatment (week 72)	Measured in liters.
Semaglutide 7.2 mg versus Placebo: Change in systolic blood pressure	From baseline (week 0) to end of treatment (week 72)	Measured in millimeters of mercury (mmHg).
Semaglutide 7.2 mg versus Placebo: Change in total cholesterol	From baseline (week 0) to end of treatment (week 72)	Measured in ratio to baseline.
Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Number of AEs	From baseline (week 0) to end of study (week 81)	Measured as count of events.
Semaglutide 7.2 mg versus Placebo: Change in triglycerides	From baseline (week 0) to end of treatment (week 72)	Measured in ratio to baseline.
Semaglutide 7.2 mg versus Placebo: Change in free fatty acids	From baseline (week 0) to end of treatment (week 72)	Measured in ratio to baseline.
Semaglutide 7.2 mg versus Placebo: Change in high-sensitivity c reactive protein (hsCRP)	From baseline (week 0) to end of treatment (week 72)	Measured in ratio to baseline.
Semaglutide 7.2 mg versus Placebo: Number of adverse events (AEs)	From baseline (week 0) to end of study (week 81)	Measured as count of events.
Semaglutide 7.2 mg versus Placebo: Change in glycated haemoglobin (HbA1c)	From baseline (week 0) to end of treatment (week 72)	Measured in percentage (%).
Semaglutide 7.2 mg versus Placebo: Change in fasting serum insulin	From baseline (week 0) to end of treatment (week 72)	Measured in ratio to baseline.
Semaglutide 7.2 mg versus Placebo: Number of participants with change in lipid-lowering treatment (decrease, no change, increase)	From baseline (week 0) to end of treatment (week 72)	Measured as count of participants.
Semaglutide 7.2 mg versus Placebo: Change in fasting plasma glucose	From baseline (week 0) to end of treatment (week 72)	Measured in milligrams per deciliter (mg/dL).
Semaglutide 7.2 mg versus Placebo: Number of participants with change in antihypertensive treatment (decrease, no change, increase)	From baseline (week 0) to end of treatment (week 72)	Measured as count of participants.
Semaglutide 7.2 mg versus Placebo: Number of participants with change in glycaemic category (Normo-glycaemia, pre-diabetes, type 2 diabetes [T2D])	From baseline (week 0) to end of treatment (week 72)	Measured as count of participants.
Semaglutide 7.2 mg versus Placebo: Number of serious adverse events (SAEs)	From baseline (week 0) to end of study (week 81)	Measured as count of events.
Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Number of SAEs	From baseline (week 0) to end of study (week 81)	Measured as count of events.
Semaglutide 7.2 mg versus Placebo: Change in pulse	From baseline (week 0) to end of treatment (week 72)	Measured in beats per minute (bmp).

Trial Locations

Locations (100)

Acibadem City Clinic MHAT Tokuda Department of Endocrinology; 🇧🇬 Sofia, Bulgaria

Medical centre "Medical arts medico-dental centre"; 🇧🇬 Sofia, Bulgaria

"Medical Center Medical Plus" Eood; 🇧🇬 Varna, Bulgaria

PANSTWOWY INSTYTUT MEDYCZNY MSWiA; 🇵🇱 Warszawa, Poland

Institut klinické a experimentalni mediciny; 🇨🇿 Praha 4, Czechia

Poliklinika Michnova - Obezitologie; 🇨🇿 Praha 4, Czechia

Fledip s.r.o.; 🇨🇿 Praha, 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, Dr. med. 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 Vármegye, Hungary

Belinus Bt.; 🇭🇺 Debrecen, Hajdu-Bihar Varmegye, 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

NZOZ "CenterMed Lublin" Sp. z o.o.; 🇵🇱 Lublin, Lubelskie, Poland

NZOZ Przychodnia Specjalistyczna Medica; 🇵🇱 Lublin, Lubelski, Poland

Med. Cent. Diabet. Endo. Metabol. DIAB-ENDO-MET; 🇵🇱 Krakow, Malopolskie, Poland

Kresmed Sp. z o. o.; 🇵🇱 Bialystok, Podlaskie, Poland

Centrum Medyczne Pratia Gdynia; 🇵🇱 Gdynia, Pomorskie, Poland

Uniwersyteckie Centrum Kliniczne SUM w Katowicach; 🇵🇱 Katowice, Poland

NBR Polska Tomasz Klodawski; 🇵🇱 Warszawa, Poland

APDP - Associação Protectora dos Diabéticos de Portugal; 🇵🇹 Lisboa, Portugal

MUDr. Dagmar Prokesova, Endokrinologicka ambulancia; 🇸🇰 Bratislava, Slovakia

MEDIMAD, s.r.o., Endokrinologicka ambulancia; 🇸🇰 Bratislava, Slovakia

IN-DIA s.r.o.; 🇸🇰 Lucenec, Slovakia

SIN AZUCAR s.r.o.; 🇸🇰 Malacky, Slovakia

MED-CENTRUM, s.r.o.; 🇸🇰 Martin, Slovakia

SVAJDLEROVA, s.r.o.; 🇸🇰 Presov, Slovakia

MEDIVASA, s.r.o., Angiologicka ambulancia; 🇸🇰 Zilina, Slovakia

Dom srdca, s.r.o.; 🇸🇰 Zilina, 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

Dr N.K. Gounden Medical Centre; 🇿🇦 Durban, KwaZulu Natal, South Africa

Maxwell Centre; 🇿🇦 Durban, KwaZulu-Natal, South Africa

Dr T Padayachee; 🇿🇦 Umkomaas, KwaZulu-Natal, South Africa

Endocare; 🇨🇿 Praha 4, Czechia

Midwest Inst For Clin Res; 🇺🇸 Indianapolis, Indiana, 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; 🇧🇬 Lukovit, Bulgaria

Individual Practice for medical care -Dr Elizabeta Dimitrova; 🇧🇬 Petrich, Bulgaria

"Medical center Smolyan clinical research" OOD; 🇧🇬 Smolyan, Bulgaria

Diagnostic Consulting Center Ascendent; 🇧🇬 Sofia, Bulgaria

Specialized gynaecology hospital for active treatment Dr Shterev; 🇧🇬 Sofia, Bulgaria

Edumed Broumov; 🇨🇿 Broumov, Czechia

Fakultní nemocnice Královské Vinohrady_Praha 10; 🇨🇿 Praha 10, Czechia

Unidade Local De Saude De Matosinhos E.P.E.; 🇵🇹 Senhora Da Hora, Matosinhos, Matosinhos, Portugal

Unidade Local de Saude de Sao Joao E.P.E; 🇵🇹 Porto, Portugal

Univ of Alabama Birmingham; 🇺🇸 Birmingham, 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

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

"Ambulatory for individual practice and specialized medical care 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