Research Study to Investigate How Well Semaglutide Tablets Taken Once Daily Work in People Who Are Overweight or Living With Obesity (OASIS 1) (OASIS 1)

Efficacy and Safety of Oral Semaglutide 50 mg Once Daily in Subjects With Overweight or Obesity (OASIS 1)

This study is being conducted to see if semaglutide tablets can be used as a treatment to help people living with overweight or obesity lose weight.

This study will look at the change in participants body weight. Participants will either get semaglutide tablets (new medicine) or placebo tablets ('dummy' medicine that looks like semaglutide but has no effect on the body). For a fair comparison, people are divided into two groups at random by a computer. This process is called randomisation.

Semaglutide tablets are new medicine being tested to treat overweight and obesity. Doctors in many countries can already prescribe semaglutide tablets at lower doses to treat type 2 diabetes.

Participants will get semaglutide or placebo tablets for 68 weeks and will need to take 1 tablet every morning

In addition to taking the medicine, participants will have talks with study staff about:

• healthy food choices
• how to be more physically active
• what participants can do to lose weight The study will last for about 1½ year.Participants will have 14 clinic visits and 7 phone calls with the study doctor. Blood samples will be taken at 10 visits.

Participants will have a test to check their heart done at 3 visits. Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period. If participant is a woman and is able to become pregnant, participant will be checked for pregnancy via urine tests.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight
• Intervention / Treatment: Drug: Oral semaglutide; Drug: Placebo (semaglutide)

• Study Type: Interventional
• Enrollment (Actual): 667
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3Z 2N6
      • Ocean West Research Clinic
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G 1A7
      • G.A. Research Associates Ltd.
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Health Authority
  • Ontario
    • Hamilton, Ontario, Canada, L8M 1K7
      • Premier Clinical Trial Research Network (PCTRN)
    • Hamilton, Ontario, Canada, L8L 5G8
      • Wharton Medical Clinic Clinical Trials (Hamilton)
• Denmark
  • Hellerup, Denmark, 2900
    • Gentofte Hospital - Center for Klinisk Metabolisk Forskning
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital Endokrinologisk forsknings afsnit 159
  • Slagelse, Denmark, 4200
    • Slagelse Sygehus Ambulatorium for hjertesygdomme
  • Region Sjælland
    • Køge, Region Sjælland, Denmark, 4600
      • Sjællands Universitetshospital, Køge - Medicinsk Afdeling
• Finland
  • Helsinki, Finland, 00014
    • Obesity Research Unit
  • Jyväskylä, Finland, 40620
    • StudyCor
  • Seinäjoki, Finland, 60220
    • Seinäjoen keskussairaala
• France
  • Le Coudray, France, 28630
    • Les Hopitaux de Chartres-Hopital Louis Pasteur
  • Le Creusot, France, 71200
    • Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-2
  • Le Creusot, France, 71200
    • Fondation Hôtel-Dieu
  • Pessac, France, 33600
    • Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-2
  • Saint-Herblain, France, 44800
    • Centre Hospitalier Universitaire de Nantes-Hopital Nord Laennec
  • Toulouse, France, 31054
    • Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-2
  • Vénissieux, France, 69200
    • Centre de Recherche Clinique Portes Du Sud
• Germany
  • Essen, Germany, 45136
    • InnoDiab Forschung Gmbh
  • Essen, Germany, 45219
    • Praxis Dr. med. M. Esser
  • Hamburg, Germany, 22041
    • Diabetes Zentrum Wandsbek Berufsausuebungsgemeinschaft GbR
  • Hohenmölsen, Germany, 06679
    • Dr. Milek medikum
  • Oldenburg in Holstein, Germany, 23758
    • RED-Institut für medizinische Forschung und Fortbildung GmbH
  • Rehlingen-Siersburg, Germany, 66780
    • Praxis Dr. med. Wenzl-Bauer
  • Stuttgart, Germany, 70378
    • MZM Praxis Drs. Erlinger
  • Wangen, Germany, 88239
    • Zentrum für klinische Studien Allgäu Oberschwaben
• Japan
  • Chiba-shi, Chiba, Japan, 260-8677
    • Chiba University Hospital_Diabetes, Metabolism and Endocrinology
  • Chiyoda-ku, Tokyo, Japan, 101-0065
    • Suidoubashi Medical Clinic_Internal Medicine
  • Tokyo, Japan, 169-0072
    • Higashi-Shinjuku Clinic
• Poland
  • Lodz, Poland, 90-338
    • Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.
  • Lubelski
    • Lublin, Lubelski, Poland, 20-538
      • NZOZ Przychodnia Specjalistyczna Medica
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-281
      • Gabinet Leczenia Otylosci i Chorob Dietozaleznych
  • Pomeranian Voivodeship
    • Gdynia, Pomeranian Voivodeship, Poland, 81-338
      • Centrum Medyczne Pratia Gdynia
  • Wielkopolskie Voivodeship
    • Poznan, Wielkopolskie Voivodeship, Poland, 60-589
      • Centrum Zdrowia Metabolicznego Paweł Bogdański
• Russia
  • Dzerzhinskiy, Russia, 140091
    • LLC "Clinic of new technologies in Medicine"
  • Moscow, Russia, 117292
    • FSBI 'I.I. Dedov National Medical Research Center of Endocrinology' of the MH of Russia
  • Moscow, Russia, 119034
    • Endocrinological Dispensary of Department of healthcare ser.
  • Moscow, Russia, 127486
    • Federal Bureau for Medical and Social Expertise
  • Saint Petersburg, Russia, 194291
    • Leningrad Regional Clinical Hospital
  • Saint Petersburg, Russia, 190013
    • Joint Stock Company "Polyclinic Complex"
  • Yekaterinburg, Russia, 620075
    • Joint Stock Company "Medical technologies"
  • Russia
    • Tyumen, Russia, Russia, 625023
      • Tumen State Medical University
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Univ of Alabama Birmingham
  • California
    • Los Angeles, California, United States, 90017
      • Velocity Clin Res Los Angeles
  • Florida
    • Kissimmee, Florida, United States, 34744
      • The Chappel Group Research
    • Plantation, Florida, United States, 33324
      • Clinical Trial Res Assoc,Inc
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East West Med Res Inst
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Inst For Clin Res
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Accellacare
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-3317
      • The University of Penn Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Res-Dallas
  • Virginia
    • Arlington, Virginia, United States, 22206
      • Washington Cntr Weight Mgmt
    • Winchester, Virginia, United States, 22601-3834
      • Selma Medical Associates
  • Washington
    • Olympia, Washington, United States, 98502
      • Capital Clin Res Ctr,LLC

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 greater than or equal to 18 years at the time of signing informed consent
• Body mass index (BMI):

greater than or equal to 27.0 kg/m^2 with the presence of at least one of the following weight-related complications (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease OR greater than or equal to 30.0 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 6.5% (48 mmol/mol) as measured by the central laboratory at screening
• A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral semaglutide; Participants will receive once daily semaglutide tables in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12), 25 mg (week 13-16) and 50 mg (week 17-68)	Drug: Oral semaglutide; Participants will receive a daily dose of oral semaglutide.
Placebo Comparator: Oral semaglutide placebo; All participants are given once daily dose for 68 weeks	Drug: Placebo (semaglutide); Oral placebo (semaglutide) once daily. Planned treatment duration will be 68 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Body Weight	Percentage change in body weight from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Number of Participants Who Achieved Weight Loss Greater Than or Equal (≥) 5% (Yes/No)	Number of participants who achieved weight loss greater than or equal to 5% of their baseline body weight (yes/no) at end-of-treatment (week 68) is presented.	At end-of-treatment (week 68)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved Weight Loss Greater Than or Equal (≥) 10% (Yes/No)	Number of participants who achieved weight loss greater than or equal ≥10% (Yes/No) at end-of-treatment (week 68) is presented.	At end-of-treatment (week 68)
Number of Participants Who Achieved Weight Loss Greater Than or Equal (≥) 15% (Yes/No)	Number of participants who achieved weight loss greater than or equal (≥) 15% (Yes/No) at end-of-treatment (week 68) is presented.	At end-of-treatment (week 68)
Number of Participants Who Achieved Weight Loss Greater Than or Equal (≥) 20% (Yes/No)	Number of participants who achieved weight loss greater than or equal (≥) 20% (Yes/No) at end-of-treatment (week 68) is presented.	At end-of-treatment (week 68)
Change in Waist Circumference	Change in waist circumference from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in Body Mass Index (BMI)	Change in BMI from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function	The IWQOL-Lite-CT is a 20-item, obesity-specific patient-reported outcome (PRO) instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items), and psychosocial (13 items). A 5-item subset of the physical domain, the physical-function composite is also supported. Items in the physical-function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency ("never" to "always") scale or a 5-point truth ("not at all true" to "completely true") scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better quality of life.	Baseline (week 0), end-of-treatment (week 68)
Change in Short Form 36 v2.0 Acute (SF-36) Physical Functioning Domain	Change in SF-36 v2.0 physical functioning domain from baseline (week 0) to end of treatment (week 68) is presented. The SF-36 form, assesses participants' health-related quality of life (HRQoL) on eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). The scores for SF-36v2 Acute (SF-36) are norm-based scores, i.e., scores transformed to a scale where the 2009 US general population has a mean of 50 (indicates population mean) with a SD of 10. The range of possible scores for the SF-36 Physical Functioning score is 19.03-57.60. Higher scores indicate better physical functioning. A positive change score indicates an improvement since baseline.	Baseline (week 0), end-of-treatment (week 68)
Change in Systolic Blood Pressure	Change in systolic blood pressure from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in Diastolic Blood Pressure	Change in diastolic blood pressure from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in Glycosylated Haemoglobin (HbA1c)	Change in HbA1c from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in Fasting Plasma Glucose (FPG)	Change in FPG from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in Fasting Serum Insulin (Pmol/L) - Ratio to Baseline	Change in fasting serum insulin (measured in picomoles per liter (pmol/L)) from baseline (week 0) to end-of-treatment (week 68) is presented as ratio to baseline.	Baseline (week 0), end-of-treatment (week 68)
Change in Total Cholesterol (mg/dL) - Ratio to Baseline	Change in total cholesterol (measured in milligrams per deciliter (mg/dL)) from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in High Density Lipoprotein (HDL) Cholesterol (mg/dL) - Ratio to Baseline	Change in high density lipoprotein (HDL) cholesterol (measured in milligrams per deciliter (mg/dL)) from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in Low Density Lipoprotein (LDL) Cholesterol (mg/dL) - Ratio to Baseline	Change in low density lipoprotein (LDL) cholesterol (measured in milligrams per deciliter (mg/dL)) from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in Very Low Density Lipoprotein (VLDL) Cholesterol (mg/dL) - Ratio to Baseline	Change in very low density lipoprotein (VLDL) cholesterol (measured in milligrams per deciliter (mg/dL)) from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in Triglycerides (mg/dL) - Ratio to Baseline	Change in triglycerides (measured in milligrams per deciliter (mg/dL)) from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in Free Fatty Acids (mg/dL) - Ratio to Baseline	Change in free fatty acids (measured in milligrams per deciliter (mg/dL)) from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Change in High Sensitivity C-reactive Protein (hsCRP) (mg/L) - Ratio to Baseline	Change in high sensitivity C-reactive protein (measured in Milligrams per liter (mg/L)) from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Number of Treatment Emergent Adverse Events	Number of treatment emergent adverse events from baseline (week 0) to end-of-study (week 75) is presented. An adverse event is any untoward medical occurrence in a clinical trial participant that is temporally associated with the use of an investigational medicinal product (IMP), whether or not considered related to the IMP. Treatment emergent adverse events (TEAEs): events that had onset date during on-treatment period. It is the time period in which participant was considered exposed to trial product.	From baseline (week 0) to end-of-study (week 75)
Number of Serious Adverse Events	Number of serious adverse events from baseline (week 0) to end-of-study (week 75) is presented. A serious adverse event (SAE) was defined as any event that resulted in any of the following: death, life-threatening experience, in-patient hospitalisation or prolongation of existing hospitalisation, persistent or significant disability or incapacity, congenital anomaly or birth defect or important medical event.	From baseline (week 0) to end-of-study (week 75)
Change in Body Weight - Kilogram (Kg)	Change in body weight from baseline (week 0) to end-of-treatment (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Number of Participants With Body Mass Index (BMI) Greater Than or Equal (≥) 30 at Baseline and BMI Lesser Than (<) 30 at Week 68 (Yes/no)	Number of participants who's body mass index (BMI) greater than or equal (≥) 30 at baseline and BMI lesser than (<) 30 at week 68 (yes/no) from (week 0) to end-of-treatment (week 68) is presented.	At end-of-treatment (week 68)
Change in Pulse	Change in pulse from baseline (week 0) to end-of-study (week 68) is presented.	Baseline (week 0), end-of-treatment (week 68)
Number of Participants at Baseline and End of Treatment in Glycaemic Category (Normo-glycaemia, Pre-diabetes, Type 2 Diabetes)	Number of participants in glycaemic categories, "normo-glycaemia, pre-diabetes and type 2 diabetes" at baseline (week 0) and end-of-treatment (week 68) are presented. These categories were set as per the following criteria: 1) Normo-glycaemia: glycated haemoglobin (HbA1c) less than (<) 5.7%; 2) Pre-diabetes: HbA1c 5.7 - 6.4% (both inclusive); 3) Type 2 diabetes: HbA1c greater than or equal to (>=) 6.5%.	Baseline (week 0), end-of-treatment (week 68)
Number of Participants With Change in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT) Physical Function Domain (PFD) Greater Than or Equal (≥) 14.6 (Yes/No)	The IWQOL-Lite-CT (measured as score on a scale) is a 20-item, obesity-specific PRO instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items), and psychosocial (13 items). A 5-item subset of the physical domain, the physical-function composite is also supported. Items in the physical-function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency ("never" to "always") scale or a 5-point truth ("not at all true" to "completely true") scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better quality of life.	At end-of-treatment (week 68)
Number of Participants With Change in Short Form 36 v2.0 Acute (SF-36) Physical Functioning Score Greater Than or Equal (≥) 3.7 (Yes/No)	Number of participants with change in SF-36 v2.0 physical functioning score ≥ 3.7 (yes/no) is presented. The SF-36 form, assesses participants' health-related quality of life (HRQoL) on eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). A positive change score indicates an improvement since baseline. The scores for SF-36v2 Acute (SF-36) are norm-based scores, i.e., scores transformed to a scale where the 2009 US general population has a mean of 50 and an SD of 10. The range of possible scores for the SF-36 Physical Functioning score is 19.03-57.60. Higher scores indicate better physical functioning.	From baseline (week 0) to end-of-treatment (week 68)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 1452), Novo Nordisk A/S

Publications and helpful links

General Publications

• Knop FK, Aroda VR, do Vale RD, Holst-Hansen T, Laursen PN, Rosenstock J, Rubino DM, Garvey WT; OASIS 1 Investigators. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Aug 26;402(10403):705-719. doi: 10.1016/S0140-6736(23)01185-6. Epub 2023 Jun 26.

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2021
• Primary Completion (Actual): March 24, 2023
• Study Completion (Actual): May 12, 2023

Study Registration Dates

• First Submitted: August 30, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Glucagon-Like Peptide-1 Receptor Agonists; semaglutide
• Other Study ID Numbers: NN9932-4737; U1111-1253-1670 (Other Identifier: World Health Organization (WHO)); 2020-002953-11 (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