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: Completed
• 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 EOOD
  • Petrich, Bulgaria, 2850
    • IPMC - Dr. Elizabeta Dimitrova
  • Smolyan, Bulgaria, 4700
    • Medical center Smolyan clinical research OOD
  • Sofia, Bulgaria, 1202
    • DCC Ascendent OOD
  • Sofia, Bulgaria, 1330
    • SGHAT Dr. Shterev EOOD
  • Sofia, Bulgaria, 1618
    • Medical Centre Medical Arts Medico-dental centre
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic UMHAT Tokuda EAD, Endocrinology
  • Varna, Bulgaria, 9010
    • AIPSMC Dr. Evelina Zlatanova EOOD
  • Varna, Bulgaria, 9000
    • Medical Center Medical Plus 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
    • Hamilton, Ontario, Canada, L8L 5G4
      • Premier Clinical Trial Research Network (PCTRN)
    • Hamilton, Ontario, Canada, L8L 5G8
      • Wharton Medical Clinic Clinical Trials (Hamilton)
    • London, Ontario, Canada, N5W 6A2
      • Milestone Research
• Czechia
  • Benátky Na Jizerou, Czechia, 29471
    • Ordinace praktického lékaře
  • Broumov, Czechia, 550 01
    • Edumed Broumov
  • Prague, Czechia, 160 00
    • Fledip s.r.o.
  • Prague, Czechia, 10034
    • Fakultní nemocnice Královské Vinohrady_Praha 10
  • Prague, Czechia, 140 00
    • Endocare
  • Prague, Czechia, 14021
    • Institut klinicke a experimentalni mediciny
  • Prague, 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 - Schwerpunktpraxis für Diabetologie und Ernährungsmedizin
  • 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, Kahrmann
• Greece
  • Athens, Greece, 11527
    • Gen Hospital of Athens Laiko,1st Dpt. of Propaedeutic Inter
  • Athens, Greece, 15125
    • Iatriko Athinon (Athens Medical Canter)
  • Athens, Greece, 17562
    • Iatriko Athinon 'Palaiou Falirou'
  • Lamia, Greece, 35100
    • General Hospital of Lamia
  • Thessaloniki, Greece, 54636
    • AHEPA General University Hospital
  • Thessaloniki, Greece, 57001
    • "Thermi" Private Hosital
  • Thessaloniki, Greece, 54642
    • "Ippokrateio" G.H. of Thessaloniki
  • Thessaloniki, Greece, 54635
    • General Hospital of Thessaloniki 'G. Gennimatas
  • Attica
    • Athens, Attica, Greece, 12462
      • University Hospital of Athens ATTIKON
• 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 county
    • Baja, Bács-Kiskun county, Hungary, 6500
      • Lausmed Kft.
  • Hajdú-Bihar
    • Debrecen, Hajdú-Bihar, 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
  • Warsaw, Poland, 00-710
    • NBR Polska Tomasz Klodawski
  • Warsaw, Poland, 02-507
    • PANSTWOWY INSTYTUT MEDYCZNY MSWiA
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-261
      • Med. Cent. Diabet. Endo. Metabol. DIAB-ENDO-MET
  • Lubelski
    • Lublin, Lubelski, Poland, 20-538
      • NZOZ Przychodnia Specjalistyczna Medica
  • Lublin Voivodeship
    • Lublin, Lublin Voivodeship, Poland, 20-044
      • NZOZ "CenterMed Lublin" Sp. z o.o.
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-481
      • Kresmed Sp. z o. o.
  • Pomeranian Voivodeship
    • Gdynia, Pomeranian Voivodeship, Poland, 81-338
      • Centrum Medyczne Pratia Gdynia
• Portugal
  • Lisbon, Portugal, 1250-230
    • APDP - Associação Protectora dos Diabéticos de Portugal
  • Lisbon, Portugal, 1349-019
    • Unidade Local De Saúde De Lisboa Ocidental E.P.E. - Hospital Egas Moniz
  • Lisbon, Portugal, 1500-650
    • Hospital da Luz Lisboa, S.A.
  • Porto, Portugal, 4200-319
    • ULS De São João, E.P.E. - Hospital de São João
  • Vila Nova de Gaia, Portugal, 4400-346
    • Hospital da Luz Arrabida, S.A.
  • Matosinhos
    • Senhora Da Hora, Matosinhos, Matosinhos, Portugal, 4464-513
      • ULS De Matosinhos E.P.E.- Hospital Pedro Hispano
• Slovakia
  • Bratislava, Slovakia, 821 01
    • MUDr. Dagmar Prokesova, Endokrinologicka ambulancia
  • Bratislava, Slovakia, 842 31
    • MEDIMAD, s.r.o., Endokrinologicka ambulancia
  • Lučenec, Slovakia, 984 01
    • IN-DIA s.r.o.
  • Malacky, Slovakia, 901 01
    • SIN AZUCAR s.r.o.
  • Martin, Slovakia, 036 01
    • MED-CENTRUM, s.r.o.
  • Prešov, Slovakia, 080 01
    • SVAJDLEROVA, s.r.o.
  • Žilina, Slovakia, 010 01
    • MEDIVASA, s.r.o., Angiologicka ambulancia
  • Žilina, 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, 4092
      • Precise Clinical Solutions (Pty) Ltd
    • Durban, KwaZulu-Natal, South Africa, 4901
      • Lenmed Shifa Private Hospital
    • Durban, KwaZulu-Natal, South Africa, 4093
      • Dr N.K. Gounden Medical Centre
    • eMkhomazi, 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.
    • Montgomery, Alabama, United States, 36106
      • Chambliss 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
  • New York
    • Albany, New York, United States, 12203
      • AMC Community Endocrinology
  • 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	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 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)	Number of participants who achieve body weight reduction >=10% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction >=10% and "no" defines participants who did not achieve body weight reduction >=10%.	At week 72
Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=15% (Yes/no)	Number of participants who achieve body weight reduction >=15% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction >=15% and "no" defines participants who did not achieve body weight reduction >=15%.	At week 72
Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=20% (Yes/no)	Number of participants who achieve body weight reduction >=20% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction >=20% and "no" defines participants who did not achieve body weight reduction >=20%.	At week 72
Semaglutide 7.2 mg Versus Placebo: Number of Participants Who Achieve Body Weight Reduction >=25% (Yes/no)	Number of participants who achieve body weight reduction >=25% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction >=25% and "no" defines participants who did not achieve body weight reduction >=25%.	At week 72
Semaglutide 7.2 mg Versus Placebo: Change in Waist Circumference	Change in waist circumference 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 Semaglutide 2.4 mg: 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 Semaglutide 2.4 mg: Number of Participants Who Achieve Body Weight Reduction >=20% (Yes/no)	Number of participants who achieve body weight reduction >=20% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction >=20% and "no" defines participants who did not achieve body weight reduction >=20%.	At week 72
Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of Participants Who Achieve Body Weight Reduction >=25% (Yes/no)	Number of participants who achieve body weight reduction >=25% from baseline (week 0) is presented in categories as "yes" or "no" where "yes" defines participants who achieved body weight reduction >=25% and "no" defines participants who did not achieve body weight reduction >=25%.	At week 72
Semaglutide 7.2 mg Versus Placebo: Change in Body Weight	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: Change in Body Mass Index (BMI)	Change in BMI 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 Semaglutide 2.4 mg: Change in Body Weight	Change in body weight from baseline (week 0) to end of treatment (week 72) is presented.	Baseline (week 0), End of treatment (week 72)
Pooled Semaglutide Versus Placebo: Change in Total Fat Volume (%)	Change in total fat volume (%) from baseline (week 0) to end of treatment (week 72) is presented.	Baseline (week 0), End of treatment (week 72)
Pooled Semaglutide Versus Placebo: Change in Total Fat Volume (Liters)	Change in total fat volume (liters) from baseline (week 0) to end of treatment (week 72) is presented.	Baseline (week 0), End of treatment (week 72)
Pooled Semaglutide Versus Placebo: Change in Lean Body Volume (%)	Change in lean body volume (%) from baseline (week 0) to end of treatment (week 72) is presented.	Baseline (week 0), End of treatment (week 72)
Pooled Semaglutide Versus Placebo: Change in Lean Body Volume (Liters)	Change in lean body volume (liters) from baseline (week 0) to end of treatment (week 72) is presented.	Baseline (week 0), End of treatment (week 72)
Pooled Semaglutide Versus Placebo: Change in Visceral Fat Volume (%)	Change in visceral fat volume (%) from baseline (week 0) to end of treatment (week 72) is presented.	Baseline (week 0), End of treatment (week 72)
Pooled Semaglutide Versus Placebo: Change in Visceral Fat Volume (Liters)	Change in visceral fat volume (liters) from baseline (week 0) to end of treatment (week 72) is presented.	Baseline (week 0), End of treatment (week 72)
Pooled Semaglutide Versus Placebo: Change in Body Weight (%)	Change in body weight (%) from baseline (week 0) to end of treatment (week 72) is presented.	Baseline (week 0), End of treatment (week 72)
Pooled Semaglutide Versus Placebo: Change in Body Weight (Kg)	Change in body weight (Kg) 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: Change in Systolic Blood Pressure	Change in systolic blood pressure 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: Change in Diastolic Blood Pressure	Change in diastolic blood pressure 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: Change in Total Cholesterol (Milligram Per Deciliter [mg/dL]) - Ratio to Baseline	Change in total cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Change in Total Cholesterol (Millimoles Per Liter [mmol/L]) - Ratio to Baseline	Change in total cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Change in High-density Lipoprotein (HDL) Cholesterol (mg/dL) - Ratio to Baseline	Change in HDL cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Change in High-density Lipoprotein (HDL) Cholesterol (mmol/L) - Ratio to Baseline	Change in HDL cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Change in Low-density Lipoprotein (LDL) Cholesterol (mg/dL)- Ratio to Baseline	Change in LDL cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Change in Low-density Lipoprotein (LDL) Cholesterol (mmol/L)- Ratio to Baseline	Change in LDL cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Change in Very Low-density Lipoprotein (VLDL) Cholesterol (mg/dL) - Ratio to Baseline	Change in VLDL cholesterol in mg/dL from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Change in Very Low-density Lipoprotein (VLDL) Cholesterol (mmol/L) - Ratio to Baseline	Change in VLDL cholesterol in mmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Change in Triglycerides (mg/dL) - Ratio to Baseline	Change in triglycerides in mg/dL from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Change in Triglycerides (mmol/L) - Ratio to Baseline	Change in triglycerides in mmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Change in High-sensitivity C-reactive Protein (hsCRP) - Ratio to Baseline	Change in hsCRP (milligram per liter [mg/L]) from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Number of Participants With Change in Lipid-lowering Treatment (Decrease, no Change, Increase)	Number of participants with change in lipid-lowering treatment from baseline (week 0) is presented in categories as decrease, no change and increase.	At week 72
Semaglutide 7.2 mg Versus Placebo: Number of Participants With Change in Antihypertensive Treatment (Decrease, no Change, Increase)	Number of participants with change in antihypertensive treatment from baseline (week 0) is presented in categories as decrease, no change and increase.	At week 72
Semaglutide 7.2 mg Versus Placebo: Change in Glycated Haemoglobin (HbA1c)	Change in HbA1c 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: Change in Fasting Plasma Glucose	Change in fasting plasma glucose 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: Change in Fasting Serum Insulin (Picomoles Per Liter [Pmol/L]) - Ratio to Baseline	Change in fasting serum insulin in pmol/L from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Change in Fasting Serum Insulin (Milliinternational Units Per Milliliter [mIU/mL]) - Ratio to Baseline	Change in fasting serum insulin in mIU/ml from baseline (week 0) to end of treatment (week 72) is presented as ratio to baseline (week 0).	Baseline (week 0), End of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Number of Participants With Change in Glycaemic Category (Normo-glycaemia, Pre-diabetes)	Number of participants with change in glycaemic category from baseline (week 0) to the end of treatment (week 72) is presented. These categories were set as per the following criteria: 1) Normo-glycaemia: glycated haemoglobin (HbA1c) <5.7%; 2) Pre-diabetes: 5.7% <= HbA1c < 6.5%	Baseline (week 0), end of treatment (week 72)
Semaglutide 7.2 mg Versus Placebo: Number of Adverse Events (AEs)	Number of AEs is reported. An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP.	From baseline (week 0) to end of study (week 81)
Semaglutide 7.2 mg Versus Placebo: Number of Serious Adverse Events (SAEs)	Number of SAEs is reported. A SAE is any untoward medical occurrence that fulfils at least one of the following criteria: results in death, is life threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical event.	From baseline (week 0) to end of study (week 81)
Semaglutide 7.2 mg Versus Placebo: Change in Pulse	Change in pulse 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 Semaglutide 2.4 mg: Number of AEs	Number of AEs is reported. An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of IMP, whether or not considered related to the IMP.	From baseline (week 0) to end of study (week 81)
Semaglutide 7.2 mg Versus Semaglutide 2.4 mg: Number of SAEs	Number of SAEs is reported. A SAE is any untoward medical occurrence that fulfils at least one of the following criteria: results in death, is life threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical event.	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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2023
• Primary Completion (Actual): October 30, 2024
• Study Completion (Actual): November 26, 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 23, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; 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