Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— PIONEER 3  

Official title:

Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02607865
• Other study ID #: NN9924-4222
• Secondary ID: 2015-001351-71U1
• Status: Completed
• Phase: Phase 3
• Start date: February 15, 2016
• Est. completion date: March 28, 2018

Study information

• Verified date: July 2022
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted globally. The aim of the trial is to investigate efficacy and long-term safety of oral semaglutide versus sitagliptin in subjects with type 2 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1864
• Est. completion date: March 28, 2018
• Est. primary completion date: February 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female, age at least 18 years at the time of signing informed consent For Japan only: Male or female, age at least 20 years at the time of signing informed consent

• Diagnosed with T2DM (type 2 diabetes mellitus) for at least 90 days prior to day of screening

• HbA1c (glycosylated haemoglobin) 7.0-10.5 % (53-91 mmol/mol) (both inclusive).

• Stable daily dose of metformin (equal or above 1500 mg or maximum tolerated dose as documented in subject medical record) alone or in combination with SU (= half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record) within 90 days prior to the day of screening

Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice). For certain specific countries: Additional specific requirements apply

• Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN 2) or Medullary Thyroid Carcinoma (MTC)

• History of pancreatitis (acute or chronic)

• History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)

• Any of the following: myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischaemic attack within the past 180 days prior to the day of screening

• Subjects presently classified as being in New York Heart Association (NYHA) Class IV.

• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening.

• Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

• History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinomas)

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• semaglutide
Oral administration once-daily
• sitagliptin
Oral administration once-daily
• placebo
Oral administration once-daily

Locations

Country	Name	City	State
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Capital Federal
Argentina	Novo Nordisk Investigational Site	Cordoba
Argentina	Novo Nordisk Investigational Site	Córdoba
Brazil	Novo Nordisk Investigational Site	São Paulo	Sao Paulo
France	Novo Nordisk Investigational Site	Angers
France	Novo Nordisk Investigational Site	Chalons-en-Champagne Cedex
France	Novo Nordisk Investigational Site	DIJON cedex
France	Novo Nordisk Investigational Site	LA ROCHE-sur-YON cedex 9
France	Novo Nordisk Investigational Site	LA ROCHELLE cedex
France	Novo Nordisk Investigational Site	Le Creusot
France	Novo Nordisk Investigational Site	Limoges
France	Novo Nordisk Investigational Site	Marseille
France	Novo Nordisk Investigational Site	Nanterre
France	Novo Nordisk Investigational Site	Nantes
France	Novo Nordisk Investigational Site	Nantes Cedex 01
France	Novo Nordisk Investigational Site	Narbonne
France	Novo Nordisk Investigational Site	Paris
France	Novo Nordisk Investigational Site	Périgueux
France	Novo Nordisk Investigational Site	PERPIGNAN cedex
France	Novo Nordisk Investigational Site	Venissieux
Germany	Novo Nordisk Investigational Site	Bad Mergentheim
Germany	Novo Nordisk Investigational Site	Berlin
Germany	Novo Nordisk Investigational Site	Dresden
Germany	Novo Nordisk Investigational Site	Elsterwerda
Germany	Novo Nordisk Investigational Site	Essen
Germany	Novo Nordisk Investigational Site	Falkensee
Germany	Novo Nordisk Investigational Site	Friedrichsthal
Germany	Novo Nordisk Investigational Site	Hamburg
Germany	Novo Nordisk Investigational Site	Leipzig
Germany	Novo Nordisk Investigational Site	Münster
Germany	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach
Germany	Novo Nordisk Investigational Site	Stuttgart
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Bhubaneshwar	Orissa
India	Novo Nordisk Investigational Site	Chandigarh	Punjab
India	Novo Nordisk Investigational Site	Chennai	Tamil Nadu
India	Novo Nordisk Investigational Site	Chennai	Tamil Nadu
India	Novo Nordisk Investigational Site	Gurgaon	Haryana
India	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh
India	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh
India	Novo Nordisk Investigational Site	Jaipur	Rajasthan
India	Novo Nordisk Investigational Site	Jaipur	Rajasthan
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	New Dehli	New Delhi
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Vellore	Tamil Nadu
Israel	Novo Nordisk Investigational Site	Haifa
Israel	Novo Nordisk Investigational Site	Holon
Israel	Novo Nordisk Investigational Site	Jerusalem
Israel	Novo Nordisk Investigational Site	Kfar Saba
Israel	Novo Nordisk Investigational Site	Petah-Tikva
Israel	Novo Nordisk Investigational Site	Ra'anana
Israel	Novo Nordisk Investigational Site	Tel Aviv
Israel	Novo Nordisk Investigational Site	Tel-Aviv
Japan	Novo Nordisk Investigational Site	Asahikawa-shi, Hokkaido
Japan	Novo Nordisk Investigational Site	Gunma
Japan	Novo Nordisk Investigational Site	Hokkaido
Japan	Novo Nordisk Investigational Site	Ibaraki
Japan	Novo Nordisk Investigational Site	Iruma-shi, Saitama
Japan	Novo Nordisk Investigational Site	Kanagawa
Japan	Novo Nordisk Investigational Site	Kashiwara-shi, Osaka
Japan	Novo Nordisk Investigational Site	Kyoto-shi, Kyoto
Japan	Novo Nordisk Investigational Site	Kyoto-shi, Kyoto
Japan	Novo Nordisk Investigational Site	Miyazaki
Japan	Novo Nordisk Investigational Site	Osaka
Japan	Novo Nordisk Investigational Site	Shinjuku-ku, Tokyo
Japan	Novo Nordisk Investigational Site	Shizuoka-shi, Shizuoka
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Mexico	Novo Nordisk Investigational Site	Aguascalientes
Mexico	Novo Nordisk Investigational Site	Ciudad Madero	Tamaulipas
Mexico	Novo Nordisk Investigational Site	Guadalajara	Jalisco
Mexico	Novo Nordisk Investigational Site	San Luis Potosi
Mexico	Novo Nordisk Investigational Site	Toluca	Estado De México
Romania	Novo Nordisk Investigational Site	Baia Mare	Maramures
Romania	Novo Nordisk Investigational Site	Bucharest
Romania	Novo Nordisk Investigational Site	Bucharest
Romania	Novo Nordisk Investigational Site	Craiova	Dolj
Romania	Novo Nordisk Investigational Site	Iasi
Romania	Novo Nordisk Investigational Site	Iasi
Romania	Novo Nordisk Investigational Site	Oradea	Bihor
Romania	Novo Nordisk Investigational Site	Pitesti	Arges
Romania	Novo Nordisk Investigational Site	Ploiesti	Prahova
Romania	Novo Nordisk Investigational Site	Satu Mare
Romania	Novo Nordisk Investigational Site	Targu Mures	Mures
Romania	Novo Nordisk Investigational Site	Timisoara	Timis
Romania	Novo Nordisk Investigational Site	Timisoara
Russian Federation	Novo Nordisk Investigational Site	Barnaul
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Penza
Russian Federation	Novo Nordisk Investigational Site	Tomsk
Russian Federation	Novo Nordisk Investigational Site	Tomsk
Russian Federation	Novo Nordisk Investigational Site	Yaroslavl
South Africa	Novo Nordisk Investigational Site	Bloemfontein	Free State
South Africa	Novo Nordisk Investigational Site	Cape Town	Western Cape
South Africa	Novo Nordisk Investigational Site	Cape Town
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Krugersdorp	Gauteng
South Africa	Novo Nordisk Investigational Site	Port Elizabeth	Eastern Cape
South Africa	Novo Nordisk Investigational Site	Pretoria
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
Turkey	Novo Nordisk Investigational Site	Ankara
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Izmir
Turkey	Novo Nordisk Investigational Site	Samsun
Ukraine	Novo Nordisk Investigational Site	Cherkasy
Ukraine	Novo Nordisk Investigational Site	Ivano-Frankivsk
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Mykolaiv
Ukraine	Novo Nordisk Investigational Site	Odesa
Ukraine	Novo Nordisk Investigational Site	Ternopil
Ukraine	Novo Nordisk Investigational Site	Zaporizhia
Ukraine	Novo Nordisk Investigational Site	Zhytomyr
United Kingdom	Novo Nordisk Investigational Site	Basingstoke
United Kingdom	Novo Nordisk Investigational Site	Cardiff
United Kingdom	Novo Nordisk Investigational Site	Chester
United Kingdom	Novo Nordisk Investigational Site	Crewe
United Kingdom	Novo Nordisk Investigational Site	Doncaster
United Kingdom	Novo Nordisk Investigational Site	Leicester
United Kingdom	Novo Nordisk Investigational Site	Plymouth
United Kingdom	Novo Nordisk Investigational Site	Preston
United Kingdom	Novo Nordisk Investigational Site	Rotherham
United Kingdom	Novo Nordisk Investigational Site	Sidcup
United Kingdom	Novo Nordisk Investigational Site	Soham
United Kingdom	Novo Nordisk Investigational Site	Swansea
United Kingdom	Novo Nordisk Investigational Site	Taunton
United Kingdom	Novo Nordisk Investigational Site	Torquay
United Kingdom	Novo Nordisk Investigational Site	Wellingborough
United States	Novo Nordisk Investigational Site	Albuquerque	New Mexico
United States	Novo Nordisk Investigational Site	Amarillo	Texas
United States	Novo Nordisk Investigational Site	Anniston	Alabama
United States	Novo Nordisk Investigational Site	Avon	Indiana
United States	Novo Nordisk Investigational Site	Birmingham	Alabama
United States	Novo Nordisk Investigational Site	Bristol	Tennessee
United States	Novo Nordisk Investigational Site	Butte	Montana
United States	Novo Nordisk Investigational Site	Carmichael	California
United States	Novo Nordisk Investigational Site	Charlotte	North Carolina
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Columbus	Ohio
United States	Novo Nordisk Investigational Site	Columbus	Ohio
United States	Novo Nordisk Investigational Site	Coronado	California
United States	Novo Nordisk Investigational Site	Corvallis	Oregon
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Denver	Colorado
United States	Novo Nordisk Investigational Site	Encino	California
United States	Novo Nordisk Investigational Site	Fargo	North Dakota
United States	Novo Nordisk Investigational Site	Flint	Michigan
United States	Novo Nordisk Investigational Site	Franklin	Ohio
United States	Novo Nordisk Investigational Site	Fresno	California
United States	Novo Nordisk Investigational Site	Gaffney	South Carolina
United States	Novo Nordisk Investigational Site	Glendale	Arizona
United States	Novo Nordisk Investigational Site	Greer	South Carolina
United States	Novo Nordisk Investigational Site	Gurnee	Illinois
United States	Novo Nordisk Investigational Site	High Point	North Carolina
United States	Novo Nordisk Investigational Site	Honolulu	Hawaii
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Humboldt	Tennessee
United States	Novo Nordisk Investigational Site	Jackson	Tennessee
United States	Novo Nordisk Investigational Site	Jefferson City	Missouri
United States	Novo Nordisk Investigational Site	Jersey Shore	Pennsylvania
United States	Novo Nordisk Investigational Site	Kissimmee	Florida
United States	Novo Nordisk Investigational Site	Lexington	Kentucky
United States	Novo Nordisk Investigational Site	Little Rock	Arkansas
United States	Novo Nordisk Investigational Site	Longview	Texas
United States	Novo Nordisk Investigational Site	Los Alamitos	California
United States	Novo Nordisk Investigational Site	Louisville	Kentucky
United States	Novo Nordisk Investigational Site	Marietta	Georgia
United States	Novo Nordisk Investigational Site	Maumee	Ohio
United States	Novo Nordisk Investigational Site	McMurray	Pennsylvania
United States	Novo Nordisk Investigational Site	Meridian	Idaho
United States	Novo Nordisk Investigational Site	Metairie	Louisiana
United States	Novo Nordisk Investigational Site	Milwaukee	Wisconsin
United States	Novo Nordisk Investigational Site	Murray	Utah
United States	Novo Nordisk Investigational Site	Natchitoches	Louisiana
United States	Novo Nordisk Investigational Site	New Port Richey	Florida
United States	Novo Nordisk Investigational Site	New Windsor	New York
United States	Novo Nordisk Investigational Site	Norman	Oklahoma
United States	Novo Nordisk Investigational Site	Olympia	Washington
United States	Novo Nordisk Investigational Site	Paducah	Kentucky
United States	Novo Nordisk Investigational Site	Paducah	Kentucky
United States	Novo Nordisk Investigational Site	Palm Harbor	Florida
United States	Novo Nordisk Investigational Site	Palm Springs	California
United States	Novo Nordisk Investigational Site	Park City	Kansas
United States	Novo Nordisk Investigational Site	Pelzer	South Carolina
United States	Novo Nordisk Investigational Site	Peoria	Illinois
United States	Novo Nordisk Investigational Site	Peoria	Illinois
United States	Novo Nordisk Investigational Site	Perry	Georgia
United States	Novo Nordisk Investigational Site	Plano	Texas
United States	Novo Nordisk Investigational Site	Plantation	Florida
United States	Novo Nordisk Investigational Site	Port Charlotte	Florida
United States	Novo Nordisk Investigational Site	Poway	California
United States	Novo Nordisk Investigational Site	Renton	Washington
United States	Novo Nordisk Investigational Site	Richmond	Virginia
United States	Novo Nordisk Investigational Site	Rochester	New York
United States	Novo Nordisk Investigational Site	Rockville	Maryland
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	Shreveport	Louisiana
United States	Novo Nordisk Investigational Site	South Burlington	Vermont
United States	Novo Nordisk Investigational Site	Spokane	Washington
United States	Novo Nordisk Investigational Site	Spring Hill	Florida
United States	Novo Nordisk Investigational Site	Statesville	North Carolina
United States	Novo Nordisk Investigational Site	Sterling Heights	Michigan
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Summerville	South Carolina
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Teaneck	New Jersey
United States	Novo Nordisk Investigational Site	Toledo	Ohio
United States	Novo Nordisk Investigational Site	Trenton	New Jersey
United States	Novo Nordisk Investigational Site	Tuscumbia	Alabama
United States	Novo Nordisk Investigational Site	Waco	Texas
United States	Novo Nordisk Investigational Site	Walnut Creek	California
United States	Novo Nordisk Investigational Site	Waltham	Massachusetts
United States	Novo Nordisk Investigational Site	West Seneca	New York
United States	Novo Nordisk Investigational Site	Whiteville	North Carolina
United States	Novo Nordisk Investigational Site	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  France,  Germany,  India,  Israel,  Japan,  Mexico,  Romania,  Russian Federation,  South Africa,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (4)

Araki E, Terauchi Y, Watada H, Deenadayalan S, Christiansen E, Horio H, Kadowaki T. Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 trials. Diabetes Obes Metab. 2 — View Citation

Aroda VR, Bauer R, Christiansen E, Haluzík M, Kallenbach K, Montanya E, Rosenstock J, Meier JJ. Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. Diabetes Obes Metab. 2022 Jul;24(7):1338-1350 — View Citation

Eliasson B, Ericsson Å, Fridhammar A, Nilsson A, Persson S, Chubb B. Long-Term Cost Effectiveness of Oral Semaglutide Versus Empagliflozin and Sitagliptin for the Treatment of Type 2 Diabetes in the Swedish Setting. Pharmacoecon Open. 2022 May;6(3):343-35 — View Citation

Rosenstock J, Allison D, Birkenfeld AL, Blicher TM, Deenadayalan S, Jacobsen JB, Serusclat P, Violante R, Watada H, Davies M; PIONEER 3 Investigators. Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabet — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c: Week 26	Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.	Week 0, week 26
Secondary	Change in Body Weight: Week 26	Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.	Week 0, week 26
Secondary	Change in HbA1c: Weeks 52 and 78	Change from baseline (week 0) in HbA1c was evaluated at weeks 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 52, week 78
Secondary	Change in Body Weight (kg): Weeks 52 and 78	Change from baseline (week 0) in body weight was evaluated at weeks 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 52, week 78
Secondary	Change in Body Weight (%)	Relative change from baseline (week 0) in body weight (kg) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in FPG	Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in BMI	Change from baseline (week 0) in body mass index (BMI) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in Waist Circumference	Change from baseline (week 0) in waist circumference was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in Total Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in total cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in LDL Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in VLDL Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in very-low-density lipoprotein (VLDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in HDL Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in Triglycerides (Ratio to Baseline)	Change from baseline (week 0) in triglycerides (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in Free Fatty Acids (Ratio to Baseline)	Change from baseline (week 0) in free fatty acids (FFA) (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Because of an issue with the handling of the blood samples for FFA, all FFA data were considered invalid for this trial; thus, no conclusion with regards to FFA levels can be made based on the data presented here.	Week 0, week 26, week 52, week 78
Secondary	Change in SMPG - Mean 7-point Profile	Change from baseline (week 0) in mean 7-point self-measured plasma glucose (SMPG) profile. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in SMPG - Mean Postprandial Increment Over All Meals	Change from baseline (week 0) in the average of the post-prandial increments over all meals was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)	Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 26, week 52, week 78
Secondary	Participants Who Achieve HbA1c =6.5% (48 mmol/Mol) AACE Target (Yes/no)	Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 26, week 52, week 78
Secondary	Participants Who Achieve Weight Loss =5% (Yes/no)	Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 26, week 52, week 78
Secondary	Participants Who Achieve Weight Loss =10% (Yes/no)	Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 26, week 52, week 78
Secondary	Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)	Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at weeks 26, 52 and 78 are presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 26, week 52, week 78
Secondary	Participants Who Achieve HbA1c Reduction =1% (10.9 mmol/Mol) and Weight Loss =3% (Yes/no)	Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 26, week 52, week 78
Secondary	Time to Additional Anti-diabetic Medication	Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26, week 0 to week 52 and week 0 to week 78. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 78), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Weeks 0-78
Secondary	Time to Rescue Medication	Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26, week 0 to week 52 and week 0 to week 78. Rescue medication was defined as any new anti-diabetic medication used as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.	Weeks 0-78
Secondary	Number of TEAEs During Exposure to Trial Product	Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 83 (78-week treatment period plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.	Weeks 0-83
Secondary	Change in Amylase (Ratio to Baseline)	Change from baseline (week 0) in amylase (units/litre (U/L)) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.	Week 0, week 26, week 52, week 78
Secondary	Change in Lipase (Ratio to Baseline)	Change from baseline (week 0) in lipase (U/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.	Week 0, week 26, week 52, week 78
Secondary	Change in Pulse Rate	Change from baseline (week 0) in pulse rate was evaluated at weeks 26, 52 and 78. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.	Week 0, week 26, week 52, week 78
Secondary	Change in SBP and DBP	Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at weeks 26, 52 and 78. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.	Week 0, week 26, week 52, week 78
Secondary	Change in ECG Evaluation	Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at weeks 26, 52 and 78. Change from baseline results are presented as shift in findings (normal, abnormal and not clinically significant (NCS) and abnormal and clinically significant (CS)) from week 0 to week 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in Physical Examination	Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (weeks -2), weeks 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system; 2) Central and peripheral nervous system; 3) Gastrointestinal system, incl. mouth; 4) General appearance; 5) Head, ears, eyes, nose, throat, neck; 6) Lymph node palpation; 7) Musculoskeletal system; 8) Respiratory system; 9) Skin; 10) Thyroid gland.	Week -2, week 52, week 78
Secondary	Change in Eye Examination Category	Participants with eye examination (fundoscopy) findings, normal, abnormal NCS and abnormal CS at baseline (week -2), week 52 and week 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week -2, week 52, week 78
Secondary	Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide binding antibodies anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Weeks 0-83
Secondary	Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide neutralising antibodies anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Weeks 0-83
Secondary	Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no)	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Weeks 0-83
Secondary	Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide neutralising antibodies cross reacting with native GLP-1 anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Weeks 0-83
Secondary	Anti-semaglutide Binding Antibody Levels	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). It is based on the data from participants who were measured with anti-semaglutide antibodies anytime during post-baseline visits (weeks 0-83). Results are presented as percentage of bound radioactivity-labelled semaglutide /total added radioactivity-labelled semaglutide (%B/T). Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Weeks 0-83
Secondary	Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes	Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-83 (78-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.	Weeks 0-83
Secondary	Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes	Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded from week 0 to week 83 (78-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.	Weeks 0-83
Secondary	Semaglutide Plasma Concentration in a Subset of the Participants for Population PK Analyses	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Semaglutide plasma concentrations for participants in the pharmacokinetic (PK) subpopulation are presented. The PK subpopulation consisted of participants from sites in Germany, Japan and the United States receiving oral semaglutide (3 mg, 7 mg or 14 mg). Results are based on the data from the on-treatment observation period and follow-up period. The on-treatment observation period was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.	Weeks 0-83
Secondary	Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 26, 52 and 78. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.	Week 0, week 26, week 52, week 78
Secondary	Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains	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 patients' quality of life within the context of clinical trials. The items of the IWQOL-Lite-CT pertain to physical functioning (physical, physical function and pain/discomfort) and psychosocial domains and all items employ a 5-point graded response scale (never, rarely, sometimes, usually, always; or not at all true, a little true, moderately true, mostly true, completely true). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 0, week 26, week 52, week 78
Secondary	Change in CoEQ: Scores From the 4 Domains and the 19 Items	Change from baseline (week 0) in Control of Eating Questionnaire (CoEQ) was evaluated at weeks (wk) 26, 52 and 78. The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control' (items 9-12, 19), 'positive mood' (items 5-8), 'craving for savoury' (items 4, 16-18) and 'craving for sweet' (items 3, 13-15). The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the data from the in-trial observation period.	Week 0, week 26, week 52, week 78

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