Research Study to Investigate How Well Semaglutide Tablets Taken Once Daily Work in East Asian People Who Are Overweight or Living With Obesity (OASIS 2)

Efficacy and Safety of Oral Semaglutide 50 mg Once Daily in East Asian Participants With Overweight or Obesity

Novo Nordisk are doing this study 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 healthcare professional.

Blood samples will be taken at 12 visits. Women cannot take part if pregnant, breast-feeding or planning to get pregnant during the study period. If participants are a woman and are able to become pregnant, participants will be checked for pregnancy via urine tests.

Study Overview

• Status: Completed
• Conditions: Overweight and Obesity
• Intervention / Treatment: Drug: semaglutide 50 mg; Drug: placebo (semaglutide)

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Ibaraki, Japan, 311-0113
    • Naka Kinen Clinic_Internal medicine
  • Minato-ku, Tokyo, Japan, 105-8470
    • Toranomon Hospital, Endocrinology and Metabolism
  • Osaka, Japan, 569-1045
    • Takatsuki Red Cross Hospital
  • Osaka, Japan, 569-1045
    • Takatsuki Red Cross Hospital_Diabetes and Endocrine Div.
  • Osaka, Japan, 565-0871
    • The University of Osaka Hospital_Metabolic Medicine
  • Tokyo, Japan, 103-0028
    • Tokyo Center Clinic
  • Tokyo, Japan, 160-0008
    • ToCROM Clinic_Internal Medicine
  • Tokyo, Japan, 103-0028
    • Tokyo Center Clinic_Internal Medicine
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 004-0004
      • Shinsapporo Seiryou Hospital_General Clinical Department
  • Kanagawa
    • Yamato-shi, Kanagawa, Japan, 242-0004
      • Tsuruma Kaneshiro Diabetes Clinic_Internal medicine
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0853
      • OCROM Clinic_Internal medicine
• South Korea
  • Daegu, South Korea, 41944
    • Kyungpook National University Hospital
  • Incheon, South Korea, 21565
    • Gachon University Gil Medical Center
  • Seoul, South Korea, 03181
    • Kangbuk Samsung Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

Participants are eligible to be included in the study only if all the following criteria apply:

• Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
• Male or female, age above or equal to 18 years at the time of signing informed consent
• Body mass index (BMI) of greater than or equal to 27.0 kg/m^2 with greater than or equal to 2 weight related comorbidities (treated or untreated) according to the JASSO guideline or BMI greater than or equal to 35.0 kg/m^2 with greater than or equal to1 weight related comorbidity (treated or untreated) according to the JASSO guideline. At least one comorbidity should be hypertension, dyslipidaemia or type 2 diabetes (T2D)
• History of at least one self-reported unsuccessful dietary effort to lose body weight

For participants with T2D at screening the following inclusion criteria apply in addition to criteria 1-4:

• Diagnosed with T2D greater than or equal to 180 days prior to screening
• Treated with either diet and exercise alone or stable treatment (same drug(s), dose and dosing frequency) for at least 60 days prior to the day of screening with up to 3 oral antidiabetic drugs (OADs) alone or in any combination (metformin, α-glucosidase (AGI), sulphonylureas (SU), glinides, SGLT2i (sodium-glucose co-transporter 2 inhibitor) or thiazolidinediones)
• HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive) as measured by central laboratory at screening

Exclusion criteria:

Participants without T2D only:

• HbA1c greater than or equal to 6.5% (48 mmol/mol) 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 prior to screening
• Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR brlow 15 ml/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO) 2012 classification by the central laboratory at screening

Participants with T2D at screening only:

• Treatment with any medication for the indication of diabetes other than stated in the inclusion criteria within the past 60 days prior to screening
• Receipt of any other anti-diabetic investigational drug within 90 days prior to screening for this study, or receipt of any investigational drugs not affecting diabetes within 30 days prior to screening for this study
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to 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 eGFR value of below 30 mL/min/1.73 m^2 according to CKD EPI creatinine equation as defined by KDIGO 2012 classification by the central laboratory at screening
• In participants treated with SGLT2i, renal impairment measured as eGFR value of below 60 mL/min/1.73 m^2 according to CKD EPI creatinine equation as defined by KDIGO 2012 classification by the central laboratory at screening

The following criteria apply to all participants:

Obesity-related:

• Treatment with any medication indicated for weight management within 90 days prior to screening
• Previous or planned (during the study period) obesity treatment with surgery or a weight loss device. However, the following are allowed: (1) liposuction and/or abdominoplasty, if performed greater than 1 year prior to screening, (2) lap banding, if the band has been removed greater than 1 year prior to screening, (3) intragastric balloon, if the balloon has been removed greater than 1 year prior to screening or (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed greater than 1 year prior to screening
• Uncontrolled thyroid disease per investigators discretion
• 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 50 mg once daily; All participants will get semaglutide or placebo tablets, 1 tablet every morning.	Drug: semaglutide 50 mg; Participants will have semaglutide for 68 weeks and will have 1 tablet every morning. Dose gradually increased to 50 mg.
Placebo Comparator: oral semaglutide placebo once daily; All participants will get semaglutide or placebo tablets, 1 tablet every morning.	Drug: placebo (semaglutide); Participants will have placebo tablets for 68 weeks and will have 1 tablet every morning.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Body Weight	Percent change in body weight from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site.	Baseline (week 0), week 68
Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 5% (Yes/No)	Number of participants who achieved >=5% weight reduction at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 5% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 5% weight reduction. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site.	At week 68

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 10% (Yes/No)	Number of participants who achieved >=10% weight reduction at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 10% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 10% weight reduction. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site.	At week 68
Change From Baseline in Impact of Weight on Quality of Life-Lite for Clinical Trials (IWQOL-Lite for CT) - Physical Function Domain (5-items) Score	The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patient's quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. Results for Physical Function Domain are presented in this outcome measure. The outcome measure was evaluated based on the data from in-trial observation period which is the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site.	Baseline (week 0), week 68
Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 15% (Yes/No)	Number of participants who achieved >=15% weight reduction at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 15% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 15% weight reduction. The outcome measure was evaluated based on in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	At week 68
Number of Participants Who Achieved Body Weight Reduction Greater Than or Equal (>=) to 20% (Yes/No)	Number of participants who achieved >=20% weight reduction at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved greater than or equal to 20% weight reduction, whereas 'No' infers the number of participants who have not achieved greater than or equal to 20% weight reduction. The outcome measure was evaluated based on in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	At week 68
Change From Baseline in Body Mass Index (BMI)	Change in BMI from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in Waist Circumference Measured According to the JASSO (Japan Society for the Study of Obesity) Guideline	Change in waist circumference measured according to JASSO guideline from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in Visceral Fat Area (VFA) Measured by CT Scan in a Subset of the Japanese Study Population (%)	Change in VFA measured by CT Scan in a subset of the japanese study population from baseline (week 0) to week 68 is presented in %. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in Visceral Fat Area (VFA) Measured by CT Scan in a Subset of the Japanese Study Population (Centimeter Square [cm^2])	Change in VFA measured by CT Scan in a subset of the japanese study population from baseline (week 0) to week 68 is presented in cm^2. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in Systolic Blood Pressure	Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in Diastolic Blood Pressure	Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in Glycosylated Haemoglobin (HbA1c)	Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in Total Cholesterol: Ratio to Baseline	Change in total cholesterol measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in High-Density Lipoproteins (HDL): Ratio to Baseline	Change in HDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in Low-Density Lipoproteins (LDL): Ratio to Baseline	Change in LDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in Very Low-Density Lipoproteins (VLDL): Ratio to Baseline	Change in VLDL measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in Triglycerides: Ratio to Baseline	Change in triglycerides measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in Free Fatty Acids: Ratio to Baseline	Change in free fatty acids measured as milligrams per deciliter (mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site (week 75).	Baseline (week 0), week 68
Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) : Ratio to Baseline	Change in hsCRP measured as milligrams per liter (mg/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial: the uninterrupted time interval from the date of randomisation (week 0) to the date of last contact with the study site.	Baseline (week 0), week 68
Number of Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of an investigational medicinal product (IMP), whether or not considered related to the IMP. All AEs mentioned are treatment emergent adverse events (TEAE) defined as an event with onset during the on-treatment observation period. On-treatment: the date of first trial product administration (week 0) to the date of last trial product administration (week 68) excluding potential off-treatment time intervals of more than 3 consecutive days. For the evaluation of adverse events the lag time for each on-treatment time interval is 7 weeks.	Week 0 to week 75
Number of Serious Adverse Events (SAEs)	A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. SAE results occurred from week 0 to week 75 is presented based on the on-treatment observation, which was defined as the date of first trial product administration (week 0) to the date of last trial product administration (week 68) excluding potential off-treatment time intervals of more than 3 consecutive days. For the evaluation of adverse events the lag time for each on-treatment time interval is 7 weeks.	Week 0 to week 75

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

• Kadowaki T, Heftdal LD, Ko HJ, Overvad M, Shimomura I, Thamattoor UK, Kim KK; OASIS 2 Investigators. Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes: The OASIS 2 Randomized Clinical Trial. JAMA Intern Med. 2025 Oct 1;185(10):1206-1217. doi: 10.1001/jamainternmed.2025.3599.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2021
• Primary Completion (Actual): July 11, 2023
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: November 11, 2021
• First Submitted That Met QC Criteria: November 11, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: August 13, 2026
• Last Verified: August 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; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide
• Other Study ID Numbers: NN9932-4738; U1111-1258-7561 (Other Identifier: World Health Organization (WHO))

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
• product manufactured in and exported from the U.S.: Yes