A Research Study to Look Into How Well Semaglutide Medicine Works at Different Doses in People With Type 2 Diabetes and Overweight

Investigation of Once-weekly Semaglutide S.C. Dose-Response in Patients With Type 2 Diabetes and Overweight - a Participant- and Investigator-blinded and Sponsor Open-label Study

This study compares how three doses of semaglutide work in participants with type 2 diabetes (T2D) and overweight who are taking metformin. The study will look mainly at how well participant's blood sugar and participant's body weight are controlled when they are taking the study medicine at different doses. Participants will either get semaglutide [2 milligrams (mg), 8 mg, or 16 mg] or semaglutide placebo (a dummy medicine). Participants will take the study medicine with an injection pen called NovoPen®4. The injection pen is a medical tool with a needle used to inject the study medicine under the skin. The study will last for about 52 weeks. Participants will have 13 clinic visits and 4 phone calls.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 245
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11528
    • Alexandra General Hospital, Therapeutic Clinic
  • Athens, Greece, 115 25
    • Iatriko Psychicou Private Clinic
  • 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'
  • Larissa, Greece, 41110
    • Univ Gen Hospital Larisa
  • Thessaloniki, Greece, 54642
    • 'Ippokrateio' General Hospital of Thessaloniki
  • Thessaloniki, Greece, 57001
    • "Thermi" Private Hosital
  • Thessaloniki, Greece, 54635
    • General Hospital of Thessaloniki 'G. Gennimatas
  • Thessaloniki, Greece, 57010
    • General Hospital of Thessaloniki "G.Papanikolaou"
  • Thessaloniki, Greece, 54645
    • EUROMEDICA Gen Clinic The/ki, Endocrin,Metabolism,Diabetes
  • 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, 1032
    • Szent Margit Rendelőintézet Nonprofit Kft.
  • Budapest, Hungary, 1134
    • Mh Egészségügyi Központ
  • Nagykanizsa, Hungary, 8800
    • Kanizsai Dorottya Korhaz
  • Szombathely, Hungary, 9700
    • Vas Varmegyei Markusovszky Egyetemi Oktatokorhaz
  • Csongrád-Csanád
    • Szeged, Csongrád-Csanád, Hungary, 6725
      • Szegedi Tudomanyegyetem St Györgyi Albert Klinikai Központ
  • Komárom-Esztergom
    • Komárom, Komárom-Esztergom, Hungary, 2900
      • Komaromi Selye Janos Korhaz
• Poland
  • Staszów, Poland, 28-200
    • KO-MED Centra Kliniczne Staszow
  • Warsaw, Poland, 00-710
    • NBR Polska Tomasz Klodawski
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 00-465
      • NBR Polska
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-879
      • NZOZ Vita-Diabetica Malgorzata Buraczyk
    • Bialystok, Podlaskie Voivodeship, Poland, 15-435
      • NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-648
      • Pro Familia Altera Sp. z o.o.
  • Łódź Voivodeship
    • Skierniewice, Łódź Voivodeship, Poland, 96-100
      • Clinmedica Research Sp. Z O.O.
  • Świętokrzyskie Voivodeship
    • Staszów, Świętokrzyskie Voivodeship, Poland, 28-200
      • Velocity Nova Sp. z o.o.
• Puerto Rico
  • Manatí, Puerto Rico, 00674
    • Manati Ctr For Clin Research
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham
    • Birmingham, Alabama, United States, 35294
      • Univ of Alabama Birmingham
  • California
    • Banning, California, United States, 92220
      • Velocity Clinical Res-Banning
    • Chula Vista, California, United States, 91911
      • Velocity Clin Res-Chula Vista
    • Coronado, California, United States, 92118
      • Southern California Res Ctr
    • Encino, California, United States, 91436
      • Cedars-Sinai Medical Group
    • Gardena, California, United States, 90247
      • Velocity Clin Res Gardena
    • Huntington Park, California, United States, 90255
      • Nat Res Inst Huntington Park
    • La Jolla, California, United States, 92037
      • Scripps Whittier Diabetes Inst
    • Lancaster, California, United States, 93534
      • First Valley Med Grp Lancaster
    • Los Angeles, California, United States, 90017
      • Velocity Clin Res Los Angeles
    • Orange, California, United States, 92868
      • Diabetes Assoc. Med Group
    • Pomona, California, United States, 91766
      • Western University of Health Sciences
    • San Diego, California, United States, 92111
      • San Diego Family Care_San Diego
    • San Mateo, California, United States, 94401
      • Mills-Peninsula Hlth Services
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research_Spring Valley
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Colorado
    • Colorado Springs, Colorado, United States, 80906
      • Optumcare Clinical Trials,LLC-Golden
  • Florida
    • Clearwater, Florida, United States, 33761
      • Tampa Bay Medical Research
    • Clearwater, Florida, United States, 33756
      • Innovative Research of W FL
    • Coral Gables, Florida, United States, 33134
      • Alliance for Multispec Res
    • DeLand, Florida, United States, 32720
      • University Clin Res-Deland
    • Fleming Island, Florida, United States, 32003
      • Northeast Research Institute
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center Inc.
    • Jacksonville, Florida, United States, 32204
      • Northeast Res Inst. Inc.
    • Miami, Florida, United States, 33174
      • Reyes Clinical Research, Inc
    • Miami, Florida, United States, 33130
      • New Life Medical
    • Miami, Florida, United States, 33155
      • Genesis Research Center, LLC
    • Miami, Florida, United States, 33173
      • Suncoast Clinical Research, Inc.
    • Miami Lakes, Florida, United States, 33014
      • San Marcus Res Clin Miami Lakes
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solution
    • Oviedo, Florida, United States, 32765
      • Oviedo Medical Research, LLC
    • Pembroke Pines, Florida, United States, 33026
      • Family Clinical Trials
    • Saint Augustine, Florida, United States, 32080
      • Northeast Research Institute
    • Saint Augustine, Florida, United States, 32086
      • St Johns Center for Clin. Res
  • Georgia
    • Adairsville, Georgia, United States, 30103
      • Appalachian Clinical Res LLC
    • Marietta, Georgia, United States, 30067
      • Urban Family Practice Assoc
    • Suwanee, Georgia, United States, 30024
      • Herman Clinical Research LLC
  • Idaho
    • Idaho Falls, Idaho, United States, 83404-7596
      • Rocky Mt Clin Res, LLC
    • Meridian, Idaho, United States, 83646
      • Solaris Clinical Research
    • Meridian, Idaho, United States, 83642
      • Velocity Clinical Res Boise
  • Illinois
    • Addison, Illinois, United States, 60101
      • Biofortis Clinical Research
    • Chicago, Illinois, United States, 60607
      • Cedar-Crosse Research Center
  • Iowa
    • Council Bluffs, Iowa, United States, 51501
      • West Broadway Clinic
    • West Des Moines, Iowa, United States, 50266
      • Iowa Diab & Endo Res Center
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Diab & Endo Ctr
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • The Research Group of Lexington LLC
    • Louisville, Kentucky, United States, 40218
      • Norton Healthcare Research Office
  • Louisiana
    • Natchitoches, Louisiana, United States, 71457
      • Barnum Medical Research Inc.
  • Maryland
    • Hyattsville, Maryland, United States, 20782
      • MedStar Community Clin Res Ctr
    • Oxon Hill, Maryland, United States, 20745
      • MD Medical Research
    • Rockville, Maryland, United States, 20852
      • Endo And Metab Cons
  • Massachusetts
    • Boston, Massachusetts, United States, 02115-5804
      • Brigham & Women's Hospital
  • Michigan
    • Flint, Michigan, United States, 48504
      • Aa Mrc Llc
    • Flint, Michigan, United States, 48532
      • Elite Research Center
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare, PLC
    • Troy, Michigan, United States, 48098
      • Arcturus HC PLC Troy Med Res
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research LLC
  • New Jersey
    • Trenton, New Jersey, United States, 08611
      • Premier Research Inc.
  • New York
    • Albany, New York, United States, 12203
      • AMC Community Endocrinology
    • New Windsor, New York, United States, 12553
      • Mid Hudson Med Res-New Windsor
    • Northport, New York, United States, 11768
      • Northport VA Med Ctr Northport
    • West Seneca, New York, United States, 14224
      • Southgate Medical Group, LLP
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Eastowne Clinical Research Unit
    • Wilmington, North Carolina, United States, 28401
      • Accellacare
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Lillestol Research LLC
  • Ohio
    • Dayton, Ohio, United States, 45439
      • Providence Health Partners Ctr
    • Maumee, Ohio, United States, 43537
      • Advanced Med Res Maumee
  • Oregon
    • Grants Pass, Oregon, United States, 97527
      • Velocity Clin Res Grants Pass
    • Medford, Oregon, United States, 97504
      • Velocity Clinical Res Medford
  • Pennsylvania
    • Jersey Shore, Pennsylvania, United States, 17740
      • Lycoming Internal Medicine, Inc.
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson Univ Di Rsrch Ctr
    • Philadelphia, Pennsylvania, United States, 19140
      • CORE - Temple University
    • West Reading, Pennsylvania, United States, 19611
      • Tower Health
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Velocity Clinical Research Columbia
    • Greenville, South Carolina, United States, 29615
      • Velocity Clinical Research Greenville
    • Mt. Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Res Ctr
    • Myrtle Beach, South Carolina, United States, 29572
      • Trial Management Associates
    • Summerville, South Carolina, United States, 29485
      • Palmetto Clinical Research
    • Union, South Carolina, United States, 29379
      • Velocity Clinical Research Union
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Medical Research, LLC
    • Humboldt, Tennessee, United States, 38343
      • Murphy Research Center
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions
  • Texas
    • Amarillo, Texas, United States, 79106
      • Amarillo Med Spec LLP
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Res-Dallas
    • Dallas, Texas, United States, 75390-9302
      • UT Southwestern Med Cntr
    • San Antonio, Texas, United States, 78209
      • Quality Research Inc
    • San Antonio, Texas, United States, 78230
      • VIP Trials
    • San Antonio, Texas, United States, 78224
      • Briggs Clinical Research, LLC
    • San Antonio, Texas, United States, 78258
      • DCT-Stone Oak
    • Shavano Park, Texas, United States, 78231
      • Consano Clinical Research, LLC
    • Sugar Land, Texas, United States, 77479
      • Dwayne O. Williams, M.D., P.A.
    • Waco, Texas, United States, 76708
      • Hillcrest Family Health Center
  • Virginia
    • Herndon, Virginia, United States, 20171
      • Nova Health Management & Research Group, PC
    • Richmond, Virginia, United States, 23219
      • Dominion Medical Associates
    • Winchester, Virginia, United States, 22601
      • Amherst Family Practice P.C.
  • Washington
    • Spokane, Washington, United States, 99203
      • Velocity Clinical Research Spokane
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54303
      • St. Vincent Hosp-Prevea Health
    • Kenosha, Wisconsin, United States, 53144
      • Clinical Investigation Spec. Kenosha

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female.
• Aged 18-64 years (both inclusive) at the time of signing informed consent.
• Diagnosed with type 2 diabetes mellitus greater than equal to (≥) 180 days prior to the day of screening.
• Glycosylated haemoglobin (HbA1c) of 7.0 - 10.5 percentage (%) [53 - 91 millimoles per mole (mmol/mol)] (both inclusive).
• Body Mass Index (BMI) ≥ 27.0 kilograms per meter square (kg/m^2).
• Stable daily dose(s) ≥ 90 days prior to the day of screening of any metformin formulations.

Exclusion Criteria:

• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to day of screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
• Renal impairment measured as estimated glomerular filtration rate (eGFR) value of less than (<) 30 milliliters per minute (mL/min)/1.73 meter square (m^2) at screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide 2 mg; Participants will receive once-weekly semaglutide 2 mg subcutaneous (s.c.) injection.	Drug: Semaglutide; Semaglutide s.c. injection once-weekly for 40 weeks. Dose gradually increased over 24 weeks, followed by a 16 week maintenance period.
Placebo Comparator: Semaglutide placebo 2 mg; Participants will receive once-weekly semaglutide placebo 2 mg s.c. injection.	Drug: Placebo; Semaglutide placebo s.c. injection once-weekly for 40 weeks. Dose gradually increased over 24 weeks, followed by a 16 week maintenance period.
Experimental: Semaglutide 8 mg; Participants will receive once-weekly semaglutide 8 mg s.c. injection.	Drug: Semaglutide; Semaglutide s.c. injection once-weekly for 40 weeks. Dose gradually increased over 24 weeks, followed by a 16 week maintenance period.
Placebo Comparator: Semaglutide placebo 8 mg; Participants will receive once-weekly semaglutide placebo 8 mg s.c. injection.	Drug: Placebo; Semaglutide placebo s.c. injection once-weekly for 40 weeks. Dose gradually increased over 24 weeks, followed by a 16 week maintenance period.
Experimental: Semaglutide 16 mg; Participants will receive once-weekly semaglutide 16 mg s.c. injection.	Drug: Semaglutide; Semaglutide s.c. injection once-weekly for 40 weeks. Dose gradually increased over 24 weeks, followed by a 16 week maintenance period.
Placebo Comparator: Semaglutide placebo 16 mg; Participants will receive once-weekly semaglutide placebo 16 mg s.c. injection.	Drug: Placebo; Semaglutide placebo s.c. injection once-weekly for 40 weeks. Dose gradually increased over 24 weeks, followed by a 16 week maintenance period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycated Haemoglobin (HbA1c)	Change in HbA1c from baseline (week 0) to end of treatment (week 40) is presented.	Baseline (week 0) and End of treatment (week 40)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight	Change in body weight from baseline (week 0) to end of treatment (week 40) is presented.	Baseline (week 0) and End of treatment (week 40)
Number of Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a clinical study participant that is temporally associated with use of investigational medicinal products (IMP), whether or not considered related to IMP. AE can therefore be any unfavourable & unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with use of IMP. TEAE was defined as event that had onset date (or increase in severity) during on-treatment observation period. On treatment observation period data are presented. On-treatment observation period is defined as time points from first drug date until first date of end of data point sets (DPS1) or last administration of randomised treatment +63 days. DPS1 in trial is defined as all observed data points from randomisation until first date of end of study visit or date of death or date of withdrawal of informed consent or contact as defined by investigator for participants that are lost to follow up.	From baseline (week 0) up to end of study (week 49)
Number of Treatment-emergent Severe Hypoglycaemic Episodes	Number of treatment-emergent severe Hypoglycaemic episodes are presented. Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. On treatment observation period data are presented. On-treatment oberservation period is defined as time points from first drug date until the first date of end of data point sets (DPS1) or last administration of randomised treatment +63 days. DPS1 in trial is defined as all observed data points from randomisation until the first date of end of study visit or date of death or date of withdrawal of informed consent or date of last contact as defined by investigator for participants that are lost to follow up.	From baseline (week 0) up to end of study (week 49)

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): August 8, 2022
• Primary Completion (Actual): October 12, 2023
• Study Completion (Actual): December 13, 2023

Study Registration Dates

• First Submitted: July 31, 2022
• First Submitted That Met QC Criteria: July 31, 2022
• First Posted (Actual): August 3, 2022

Study Record Updates

• Last Update Posted (Actual): December 12, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide
• Other Study ID Numbers: NN9535-4984; U1111-1271-9209 (Other Identifier: World Health Organization (WHO)); 2022-000882-41 (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 novonordisk-trials.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