Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes and Moderate Renal Impairment

Diabetes Mellitus, Type 2 Clinical Trial

— PIONEER 5  

Official title:

Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes and Moderate Renal Impairment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02827708
• Other study ID #: NN9924-4234
• Secondary ID: 2015-005326-19U1
• Status: Completed
• Phase: Phase 3
• Start date: September 20, 2016
• Est. completion date: May 15, 2018

Study information

• Verified date: February 2020
• 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 this trial is to investigate efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes and moderate renal impairment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 324
• Est. completion date: May 15, 2018
• Est. primary completion date: April 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial

• Male or female, age above or equal to 18 years at the time of signing informed consent

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

• HbA1c (glycosylated haemoglobin) of 7.0-9.5% (53-80 mmol/mol) (both inclusive)

• Moderate renal impairment defined as estimated glomerular filtration rate of 30-59 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula

• Stable daily dose(s) within 90 days prior to the day of screening of any of the following treatment regimens:

• 1-2 of the following oral anti-diabetic drugs:

• Metformin equal or above 1500 mg or maximum tolerated dose documented in the subject medical record),

• Sulfonylurea (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)

• Basal insulin alone (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin) or

• Metformin (equal or above 1500 mg or maximum tolerated dose documented in the subject medical record) in combination with basal insulin (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin)

Exclusion Criteria:

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

• Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol

• Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma

• 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 hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation

• Subjects presently classified as being in New York Heart Association Class IV

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

• Subjects with alanine aminotransferase above 2.5 x upper normal limit

• Rapidly progressing renal disease (e.g. such as acute glomerulonephritis) as judged by the investigator or known nephrotic albuminuria (above 2200 mg/24 hours or above 2200 mg/g)

• Use of systemic immunosuppressive treatment within 90 days prior to screening

• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 14 days

• Known hypoglycaemic unawareness and/or recurrent severe hypoglycaemic episodes as judged by the investigator

• Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• semaglutide
Oral administration once daily.
• placebo
Oral administration once daily.

Locations

Country	Name	City	State
Denmark	Novo Nordisk Investigational Site	Aalborg
Denmark	Novo Nordisk Investigational Site	Århus C
Denmark	Novo Nordisk Investigational Site	Gentofte
Denmark	Novo Nordisk Investigational Site	Hvidovre
Denmark	Novo Nordisk Investigational Site	København S
Denmark	Novo Nordisk Investigational Site	Køge
Denmark	Novo Nordisk Investigational Site	Svendborg
Finland	Novo Nordisk Investigational Site	Ähtäri
Finland	Novo Nordisk Investigational Site	Espoo
Finland	Novo Nordisk Investigational Site	Helsinki
Finland	Novo Nordisk Investigational Site	Kerava
Finland	Novo Nordisk Investigational Site	Kuopio
Finland	Novo Nordisk Investigational Site	Oulu
Finland	Novo Nordisk Investigational Site	Turku
Israel	Novo Nordisk Investigational Site	Haifa
Israel	Novo Nordisk Investigational Site	Haifa
Israel	Novo Nordisk Investigational Site	Jerusalem
Israel	Novo Nordisk Investigational Site	Kfar Saba
Israel	Novo Nordisk Investigational Site	Rehovot
Israel	Novo Nordisk Investigational Site	Tel Hashomer
Israel	Novo Nordisk Investigational Site	Tel-Aviv
Poland	Novo Nordisk Investigational Site	Poznan
Poland	Novo Nordisk Investigational Site	Zabrze
Russian Federation	Novo Nordisk Investigational Site	Barnaul
Russian Federation	Novo Nordisk Investigational Site	Barnaul
Russian Federation	Novo Nordisk Investigational Site	Belgorod
Russian Federation	Novo Nordisk Investigational Site	Chelyabinsk
Russian Federation	Novo Nordisk Investigational Site	Dzerzhinskiy
Russian Federation	Novo Nordisk Investigational Site	Kazan
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Penza
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Tomsk
Russian Federation	Novo Nordisk Investigational Site	Ulianovsk
Russian Federation	Novo Nordisk Investigational Site	Volgograd
Russian Federation	Novo Nordisk Investigational Site	Voronezh
Russian Federation	Novo Nordisk Investigational Site	Yaroslavl
Russian Federation	Novo Nordisk Investigational Site	Yoshkar-Ola
Sweden	Novo Nordisk Investigational Site	Göteborg
Sweden	Novo Nordisk Investigational Site	Lund
Sweden	Novo Nordisk Investigational Site	Örebro
Sweden	Novo Nordisk Investigational Site	Skövde
Sweden	Novo Nordisk Investigational Site	Uppsala
Sweden	Novo Nordisk Investigational Site	Vindeln
United Kingdom	Novo Nordisk Investigational Site	Bexhill-on-Sea
United Kingdom	Novo Nordisk Investigational Site	Doncaster
United Kingdom	Novo Nordisk Investigational Site	Edinburgh
United Kingdom	Novo Nordisk Investigational Site	Glasgow
United Kingdom	Novo Nordisk Investigational Site	Hull
United Kingdom	Novo Nordisk Investigational Site	Milton Keynes
United Kingdom	Novo Nordisk Investigational Site	Rothwell
United Kingdom	Novo Nordisk Investigational Site	Sheffield
United Kingdom	Novo Nordisk Investigational Site	Wellingborough
United States	Novo Nordisk Investigational Site	Albany	New York
United States	Novo Nordisk Investigational Site	Amarillo	Texas
United States	Novo Nordisk Investigational Site	Asheboro	North Carolina
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Avon	Indiana
United States	Novo Nordisk Investigational Site	Baltimore	Maryland
United States	Novo Nordisk Investigational Site	Baltimore	Maryland
United States	Novo Nordisk Investigational Site	Bermuda Dunes	California
United States	Novo Nordisk Investigational Site	Buckley	Michigan
United States	Novo Nordisk Investigational Site	Clearwater	Florida
United States	Novo Nordisk Investigational Site	Concord	California
United States	Novo Nordisk Investigational Site	Cooper City	Florida
United States	Novo Nordisk Investigational Site	Costa Mesa	California
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Danbury	Connecticut
United States	Novo Nordisk Investigational Site	Dayton	Ohio
United States	Novo Nordisk Investigational Site	Delaware	Ohio
United States	Novo Nordisk Investigational Site	Fargo	North Dakota
United States	Novo Nordisk Investigational Site	Franklin	Ohio
United States	Novo Nordisk Investigational Site	Franklin	Indiana
United States	Novo Nordisk Investigational Site	Fresno	California
United States	Novo Nordisk Investigational Site	Gurnee	Illinois
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Kingsport	Tennessee
United States	Novo Nordisk Investigational Site	La Jolla	California
United States	Novo Nordisk Investigational Site	Lawrenceville	Georgia
United States	Novo Nordisk Investigational Site	Lebanon	New Hampshire
United States	Novo Nordisk Investigational Site	Marietta	Georgia
United States	Novo Nordisk Investigational Site	Miami Lakes	Florida
United States	Novo Nordisk Investigational Site	Midland	Texas
United States	Novo Nordisk Investigational Site	Murrells Inlet	South Carolina
United States	Novo Nordisk Investigational Site	Myrtle Beach	South Carolina
United States	Novo Nordisk Investigational Site	Nashua	New Hampshire
United States	Novo Nordisk Investigational Site	New Hyde Park	New York
United States	Novo Nordisk Investigational Site	New Port Richey	Florida
United States	Novo Nordisk Investigational Site	Norman	Oklahoma
United States	Novo Nordisk Investigational Site	Northport	New York
United States	Novo Nordisk Investigational Site	Norwalk	Connecticut
United States	Novo Nordisk Investigational Site	Olympia	Washington
United States	Novo Nordisk Investigational Site	Omaha	Nebraska
United States	Novo Nordisk Investigational Site	Orlando	Florida
United States	Novo Nordisk Investigational Site	Palm Harbor	Florida
United States	Novo Nordisk Investigational Site	Pembroke Pines	Florida
United States	Novo Nordisk Investigational Site	Richmond	Virginia
United States	Novo Nordisk Investigational Site	Roswell	Georgia
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	San Ramon	California
United States	Novo Nordisk Investigational Site	Slidell	Louisiana
United States	Novo Nordisk Investigational Site	Teaneck	New Jersey
United States	Novo Nordisk Investigational Site	Tuscumbia	Alabama
United States	Novo Nordisk Investigational Site	Waterbury	Connecticut
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
United States	Novo Nordisk Investigational Site	Winchester	Virginia
United States	Novo Nordisk Investigational Site	Winchester	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Denmark,  Finland,  Israel,  Poland,  Russian Federation,  Sweden,  United Kingdom, 

References & Publications (1)

Mosenzon O, Blicher TM, Rosenlund S, Eriksson JW, Heller S, Hels OH, Pratley R, Sathyapalan T, Desouza C; PIONEER 5 Investigators. Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placeb — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c	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 (kg)	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 FPG	Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 26. 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
Secondary	Change in Body Weight (%)	Relative change from baseline (week 0) in body weight (kg) was evaluated at week 26. 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
Secondary	Change in BMI	Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26. 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
Secondary	Change in Waist Circumference	Change from baseline (week 0) in waist circumference was evaluated at week 26. 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
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 week 26. 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
Secondary	Participants Who Achieve HbA1c =6.5% (48 mmol/Mol), AACE Target (Yes/no)	Participants who achieved HbA1c =6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no), was evaluated at week 26. 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
Secondary	Participants Who Achieve Weight Loss =5% (Yes/no)	Participants who achieved weight loss =5% of their baseline body weight (yes/no) was evaluated at week 26. 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
Secondary	Participants Who Achieve Weight Loss =10% (Yes/no)	Participants who achieved weight loss of =10% of their baseline body weight (yes/no) was evaluated at week 26. 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
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 <7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) was evaluated at week 26. 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
Secondary	Participants Who Achieve HbA1c Reduction =1% (10.9 mmol/Mol) and Weight Loss =3% (Yes/no)	Participants who achieved HbA1c reduction =1% and weight loss of =3% (yes/no) was evaluated at week 26. 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
Secondary	Change in Total Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in total cholesterol (mmol/L) at week 26 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
Secondary	Change in LDL Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at week 26 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
Secondary	Change in HDL Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at week 26 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
Secondary	Change in Triglycerides (Ratio to Baseline)	Change from baseline (week 0) in triglycerides (mmol/L) at week 26 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
Secondary	Change in CRP (Ratio to Baseline)	Change from baseline (week 0) in C-reactive protein (CRP) (mg/L) at week 26 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
Secondary	Time to Additional Anti-diabetic Medication	Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the period, from week 0 to week 26. 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 26), 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 0-26
Secondary	Time to Rescue Medication	Presented results are the number of participants who had taken rescue medication anytime during the period, from week 0 to week 26. 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 0-26
Secondary	Number of TEAEs	Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.	Weeks 0-31
Secondary	Number of 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 31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the first dose of trial product until last dose of trial product were considered treatment -emergent. Severe or BG-confirmed symptomatic hypoglycaemia was defined as an episode, that is severe according to the ADA classification or BG-confirmed by a plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. 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.	Weeks 0-31
Secondary	Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)	Number of participants with treatment emergent severe or BG-confirmed symptomatic hypoglycaemic episodes was recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the first dose of trial product until last dose of trial product were considered treatment -emergent. Severe or BG-confirmed symptomatic hypoglycaemia was defined as an episode, that is severe according to the ADA classification or BG-confirmed by a plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. 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.	Weeks 0-31
Secondary	Change in Amylase (Ratio to Baseline)	Change from baseline (week 0) in amylase (units/litre (U/L)) at week 26 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
Secondary	Change in Lipase (Ratio to Baseline)	Change from baseline (week 0) in lipase (U/L) at week 26 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
Secondary	Change in Pulse Rate	Change from baseline (week 0) in pulse rate was evaluated at week 26. 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
Secondary	Change in Blood Pressure (Systolic and Diastolic Blood Pressure)	Change from baseline (week 0) in systolic and diastolic blood pressure was evaluated at week 26. 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
Secondary	Change in Urinary Albumin to Creatinine Ratio (Ratio to Baseline)	Change from baseline (week 0) in urinary albumin to creatinine ratio (mg/mmol) at week 26 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
Secondary	Change in ECG	Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at week 26. 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. 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
Secondary	Change in Physical Examination	Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (week [wk] -2) and wk 26 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) Nervous system (central and peripheral); 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 26
Secondary	Change in Eye Examination	Participants with eye examination findings, normal, abnormal NCS and abnormal CS at baseline (week -2) and week 26 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 26
Secondary	Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)	This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide binding antibodies anytime during post-baseline visits (weeks 0-31) 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 0-31
Secondary	Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)	This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies anytime during post-baseline visits (weeks 0-31) 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 0-31
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 14 mg treatment arm. 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 0-31) 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 0-31
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 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies cross reacting with native GLP-1 anytime during post-baseline visits (weeks 0-31) 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 0-31
Secondary	Anti-semaglutide Binding Antibody Levels	This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. It is based on the data from participants who were measured with anti-semaglutide antibodies anytime during post-baseline visits (weeks 0-31). 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 0-31
Secondary	Semaglutide Plasma Concentrations for Population PK Analyses	This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Semaglutide plasma concentrations were measured at weeks 4, 8, 14 and 26. 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.	Weeks 0-26
Secondary	SNAC Plasma Concentrations	This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Sodium N-[8-(2-hydroxybenzoyl) amino]caprylate (SNAC) plasma concentrations were measured after 25 and 40 minutes post-dose at weeks 4, 14 and 26. 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.	Weeks 0-26
Secondary	Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (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 week 26. 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
Secondary	Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)	Change from baseline (week 0) in Diabetes Treatment Satisfaction Questionnaire - status version (DTSQs) was evaluated at week 26. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of hyperglycaemia and hypoglycaemia, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score has a minimum of 0 and a maximum of 36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction.	Week 0, week 26
Secondary	Change in Urinalysis	Participants with urinalysis, "leukocytes and erythrocytes" findings, negative, trace, small, moderate or large at baseline (week [wk] 0) and wk 26 are presented. Participants with urinalysis, "nitrit" findings, negative or positive at baseline (wk 0) and wk 26 are presented. 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 -2, week 26

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