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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Semaglutide; Drug: Semaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1407
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Kozloduy, Bulgaria, 3320
    • Medical centre "Zdrave 1" OOD
  • Lukovit, Bulgaria, 5770
    • Medical center Hippocrates-Lukovit
  • Petrich, Bulgaria, 2850
    • Individual Practice for medical care -Dr Elizabeta Dimitrova
  • Smolyan, Bulgaria, 4700
    • "Medical center Smolyan clinical research" OOD
  • Sofia, Bulgaria, 1202
    • Diagnostic Consulting Center Ascendent
  • Sofia, Bulgaria, 1330
    • Specialized gynaecology hospital for active treatment Dr Shterev
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic MHAT Tokuda Department of Endocrinology
  • Sofia, Bulgaria, 1618
    • Medical centre "Medical arts medico-dental centre"
  • Varna, Bulgaria, 9000
    • "Medical Center Medical Plus" Eood
  • Varna, Bulgaria, 9010
    • "Ambulatory for individual practice and specialized medical care Dr. Evelina Zlatanova" EOOD
• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3Z 2N6
      • Ocean West Research Clinic
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Health Authority
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Hlth Halifax
  • Ontario
    • Hamilton, Ontario, Canada, L8L 5G8
      • Wharton Med Clin Trials
    • Hamilton, Ontario, Canada, L8M 1K7
      • Hamilton Med Res Group
    • London, Ontario, Canada, N5W 6A2
      • Milestone Research
• Czechia
  • Benátky Na Jizerou, Czechia, 29471
    • Ordinace praktického lékaře
  • Broumov, Czechia, 550 01
    • Edumed Broumov
  • Praha, Czechia, 160 00
    • Fledip s.r.o.
  • Praha 10, Czechia, 10034
    • Fakultní nemocnice Královské Vinohrady_Praha 10
  • Praha 4, Czechia, 14021
    • Institut Klinicke a Experimentalni Mediciny
  • Praha 4, Czechia, 140 00
    • Endocare
  • Praha 4, Czechia, 149 00
    • Poliklinika Michnova - Obezitologie
• Germany
  • Berlin, Germany, 13597
    • Medizinisches Versorgungszentrum Am Bahnhof Spandau GbR
  • Elsterwerda, Germany, 04910
    • Zentrum fuer klinische Studien Suedbrandenburg GmbH
  • Essen, Germany, 45136
    • InnoDiab Forschung GmbH
  • Essen, Germany, 45219
    • Praxis Dr. med. M. Esser
  • Falkensee, Germany, 14612
    • Zentrum für klinische Forschung, Dr. med. Lüdemann
  • Münster, Germany, 48153
    • MedicalCenter am Clemenshospital
  • Oldenburg in Holstein, Germany, 23758
    • RED-Institut für medizinische Forschung und Fortbildung GmbH
  • Rehlingen-Siersburg, Germany, 66780
    • Praxis Dr. med. Wenzl-Bauer
  • Wangen, Germany, 88239
    • Zentrum für klinische Studien Allgäu Oberschwaben
  • Witten, Germany, 58455
    • Forschungszentrum Ruhr KliFoCenter GmbH, Dr. med. Kahrmann
• Greece
  • Athens, Greece, GR-15125
    • Iatriko Athinon (Athens Medical Canter)
  • Athens, Greece, GR-17562
    • Iatriko Athinon 'Palaiou Falirou'
  • Athens, Greece, GR-11527
    • Gen Hospital of Athens Laiko,1st Dpt. of Propaedeutic Inter
  • Haidari-Athens, Greece, GR-12462
    • University Hospital of Athens ATTIKON
  • Lamia, Greece, GR35100
    • General Hospital of Lamia
  • Thessaloniki, Greece, GR-54635
    • General Hospital of Thessaloniki 'G. Gennimatas
  • Thessaloniki, Greece, GR-57001
    • "Thermi" Private Hosital
  • Thessaloniki, Greece, GR-54636
    • AHEPA General University Hospital
  • Thessaloniki, Greece, GR-54642
    • "Ippokrateio" G.H. of Thessaloniki
• Hungary
  • Budapest, Hungary, 1106
    • Bajcsy-Zsilinszky Kórház
  • Budapest, Hungary, 1089
    • ClinDiab Egészségügyi Szolgáltató és Kereskedelmi Kft.
  • Budapest, Hungary, 1132
    • MED-TIMA Kft.
  • Székesfehérvár, Hungary, 8000
    • Fejér Megyei Szent György Oktatókórház
  • Bács-Kiskun Vármegye
    • Baja, Bács-Kiskun Vármegye, Hungary, 6500
      • Lausmed Kft.
  • Hajdu-Bihar Varmegye
    • Debrecen, Hajdu-Bihar Varmegye, Hungary, 4025
      • Belinus Bt.
  • Szabolcs-Szatmar Varmegye
    • Nyíregyháza, Szabolcs-Szatmar Varmegye, Hungary, 4405
      • Borbánya Praxis E.Ü. Kft.
• Norway
  • Hamar, Norway, 2317
    • Falck Norge AS
  • Oslo, Norway, 0373
    • Oslo universitetssykehus HF Aker
  • Tønsberg, Norway, 3116
    • Sykehuset i Vestfold HF, Tønsberg
• Poland
  • Katowice, Poland, 40-752
    • Uniwersyteckie Centrum Kliniczne SUM w Katowicach
  • Warszawa, Poland, 02-507
    • Panstwowy Instytut Medyczny MSWiA
  • Warszawa, Poland, 00-710
    • NBR Polska Tomasz Klodawski
  • Lubelski
    • Lublin, Lubelski, Poland, 20-538
      • NZOZ Przychodnia Specjalistyczna Medica
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-044
      • NZOZ "CenterMed Lublin" Sp. z o.o.
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-261
      • Med. Cent. Diabet. Endo. Metabol. DIAB-ENDO-MET
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-481
      • Kresmed Sp. z o. o.
  • Pomorskie
    • Gdynia, Pomorskie, Poland, 81-338
      • Centrum Medyczne Pratia Gdynia
• Portugal
  • Lisboa, Portugal, 1250-230
    • APDP - Associação Protectora dos Diabéticos de Portugal
  • Matosinhos, Portugal, 4464-513
    • Unidade Local de Saúde de Matosinhos
  • Porto, Portugal, 4200-319
    • Centro Hospitalar de São João
• Slovakia
  • Bratislava, Slovakia, 821 01
    • MUDr. Dagmar Prokesova, Endokrinologicka ambulancia
  • Bratislava, Slovakia, 842 31
    • MEDIMAD, s.r.o., Endokrinologicka ambulancia
  • Lucenec, Slovakia, 984 01
    • Diabetologicka ambulancia IN-DIA s.r.o.
  • Malacky, Slovakia, 901 01
    • SIN AZUCAR s.r.o.
  • Martin, Slovakia, 036 01
    • MED-CENTRUM, s.r.o.
  • Presov, Slovakia, 080 01
    • SVAJDLEROVA, s.r.o.
  • Zilina, Slovakia, 010 01
    • MEDIVASA, s.r.o., Angiologicka ambulancia
  • Zilina, Slovakia, 01001
    • Dom srdca, s.r.o.
• South Africa
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6001
      • Phoenix Pharma
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Medi-Clinic Bloemfontein
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1820
      • Deepak Lakha
    • Johannesburg, Gauteng, South Africa, 1827
      • Hemant Makan
    • Johannesburg, Gauteng, South Africa, 2013
      • Wits Bara Clinical Trial Site
    • Johannesburg, Gauteng, South Africa, 1818
      • Soweto Clinical Trial Centre
  • KwaZulu Natal
    • Durban, KwaZulu Natal, South Africa, 4093
      • Dr N.K. Gounden Medical Centre
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4001
      • Maxwell Centre
    • Umkomaas, KwaZulu-Natal, South Africa, 4170
      • Dr T Padayachee
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Univ of Alabama Birmingham
    • Montgomery, Alabama, United States, 36106
      • Healthscan Clinical Trials,LLC.
  • California
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Ctr for Clin Res
    • Orlando, Florida, United States, 32825
      • Florida Institute For Clinical Research LLC
    • Orlando, Florida, United States, 32825
      • Florida Inst For Clin Res LLC
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East West Med Res Inst
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Inst For Clin Res
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest Life Sciences LLC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Amarillo, Texas, United States, 79106
      • Amarillo Med Spec LLP
    • Austin, Texas, United States, 78704
      • Elligo Clin Res Centre
    • Dallas, Texas, United States, 75230
      • Velocity Clin Res, Dallas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center-CRU
    • Longview, Texas, United States, 75605
      • DCOL Ctr for Clin Res
    • Sugar Land, Texas, United States, 77479
      • Sugar Lakes Family Practice PA
  • Virginia
    • Richmond, Virginia, United States, 23294
      • National Clin Res Inc.
    • Winchester, Virginia, United States, 22601-3834
      • Selma Medical Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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, 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.; 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.
Experimental: 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.	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, 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.; 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.
Placebo Comparator: Placebo; Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Semaglutide 7.2 mg versus Placebo: Relative change in body weight	Measured in percentage (%).	From baseline (week 0) to 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)	Measured as count of participants.	From baseline (week 0) to end of treatment (week 72)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2023
• Primary Completion (Estimated): September 20, 2024
• Study Completion (Estimated): November 22, 2024

Study Registration Dates

• First Submitted: December 2, 2022
• First Submitted That Met QC Criteria: December 2, 2022
• First Posted (Actual): December 12, 2022

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Glucagon-Like Peptide-1 Receptor Agonists; Semaglutide
• Other Study ID Numbers: NN9536-4999; U1111-1274-4259 (Other Identifier: World Health Organization (WHO)); 2022-000790-94 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisktrials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No