Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus.

Diabetes Mellitus, Type 2 Clinical Trial

— PIONEER 7  

Official title:

Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02849080
• Other study ID #: NN9924-4257
• Secondary ID: 2015-005593-38U1
• Status: Completed
• Phase: Phase 3
• Start date: September 20, 2016
• Est. completion date: March 27, 2019

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 globally conducted. The aim of this trial is to investigate Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation versus Sitagliptin in Subjects with Type 2 Diabetes Mellitus.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 504
• Est. completion date: March 27, 2019
• Est. primary completion date: February 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Main phase (the inclusion criteria for the main phase are not reassessed for the extension phase):

• 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. For Korea only: Male or female, age above or equal to 19 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) 7.5-9.5% (58-80 mmol/mol) (both inclusive)

• Treatment target of HbA1c below 7.0% (53 mmol/mol), as judged by the investigator

• Stable daily dose(s) of 1-2 of the following anti-diabetic drugs within 90 days prior to the day of screening:

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

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

• Sodium glucose co-transporter 2 inhibitors

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

Extension phase:

• Informed consent for the extension phase obtained before any trial-related activities for the extension phase.

• On randomised treatment with or without rescue medication at week 52.

Exclusion Criteria:

Main phase (the exclusion criteria for the main phase are not reassessed for the extension phase):

• 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

• Renal impairment defined as Estimated Glomerular Filtration rate 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula

• 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

• 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)

• History of diabetic ketoacidosis

Extension phase: There are no new exclusion criteria for the extension phase

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

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

Locations

Country	Name	City	State
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Corrientes
Argentina	Novo Nordisk Investigational Site	Rosario
Austria	Novo Nordisk Investigational Site	Graz
Austria	Novo Nordisk Investigational Site	Saint Stefan
Austria	Novo Nordisk Investigational Site	Wien
Belgium	Novo Nordisk Investigational Site	Bonheiden
Belgium	Novo Nordisk Investigational Site	Boussu
Belgium	Novo Nordisk Investigational Site	Bruxelles
Belgium	Novo Nordisk Investigational Site	Edegem
Belgium	Novo Nordisk Investigational Site	Gent
Belgium	Novo Nordisk Investigational Site	Leuven
Belgium	Novo Nordisk Investigational Site	Liège
Brazil	Novo Nordisk Investigational Site	São Paulo	Sao Paulo
Egypt	Novo Nordisk Investigational Site	Alexandria
Egypt	Novo Nordisk Investigational Site	Cairo
Egypt	Novo Nordisk Investigational Site	Cairo
Korea, Republic of	Novo Nordisk Investigational Site	Gangwon-do
Korea, Republic of	Novo Nordisk Investigational Site	Gyeonggi-do
Korea, Republic of	Novo Nordisk Investigational Site	Pusan
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Seoul
Korea, Republic of	Novo Nordisk Investigational Site	Suwon
Norway	Novo Nordisk Investigational Site	Hamar
Norway	Novo Nordisk Investigational Site	Oslo
Norway	Novo Nordisk Investigational Site	Oslo
Norway	Novo Nordisk Investigational Site	Stavanger
Norway	Novo Nordisk Investigational Site	Trondheim
Switzerland	Novo Nordisk Investigational Site	Bern
Switzerland	Novo Nordisk Investigational Site	Einsiedeln
Switzerland	Novo Nordisk Investigational Site	Genève 14
Switzerland	Novo Nordisk Investigational Site	Luzern 16
Switzerland	Novo Nordisk Investigational Site	Olten
Switzerland	Novo Nordisk Investigational Site	St. Gallen
Switzerland	Novo Nordisk Investigational Site	St. Gallen
Switzerland	Novo Nordisk Investigational Site	Winterthur
Turkey	Novo Nordisk Investigational Site	Adana
Turkey	Novo Nordisk Investigational Site	Ankara
Turkey	Novo Nordisk Investigational Site	Antalya
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	Rize
United States	Novo Nordisk Investigational Site	Albuquerque	New Mexico
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Billings	Montana
United States	Novo Nordisk Investigational Site	Blackfoot	Idaho
United States	Novo Nordisk Investigational Site	Boynton Beach	Florida
United States	Novo Nordisk Investigational Site	Chapel Hill	North Carolina
United States	Novo Nordisk Investigational Site	Chesapeake	Virginia
United States	Novo Nordisk Investigational Site	Cleveland	Ohio
United States	Novo Nordisk Investigational Site	Corpus Christi	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Evanston	Illinois
United States	Novo Nordisk Investigational Site	Flint	Michigan
United States	Novo Nordisk Investigational Site	Glendale	Arizona
United States	Novo Nordisk Investigational Site	Greenfield	Indiana
United States	Novo Nordisk Investigational Site	Greensboro	North Carolina
United States	Novo Nordisk Investigational Site	Greenville	North Carolina
United States	Novo Nordisk Investigational Site	Henderson	Nevada
United States	Novo Nordisk Investigational Site	Kingsport	Tennessee
United States	Novo Nordisk Investigational Site	Lake Worth	Florida
United States	Novo Nordisk Investigational Site	Lancaster	California
United States	Novo Nordisk Investigational Site	Louisville	Kentucky
United States	Novo Nordisk Investigational Site	Mentor	Ohio
United States	Novo Nordisk Investigational Site	Metairie	Louisiana
United States	Novo Nordisk Investigational Site	Miami Lakes	Florida
United States	Novo Nordisk Investigational Site	Muncie	Indiana
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	Oxon Hill	Maryland
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania
United States	Novo Nordisk Investigational Site	Port Orange	Florida
United States	Novo Nordisk Investigational Site	Renton	Washington
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Wadsworth	Ohio
United States	Novo Nordisk Investigational Site	West Hills	California
United States	Novo Nordisk Investigational Site	Whiteville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Egypt,  Korea, Republic of,  Norway,  Switzerland,  Turkey, 

References & Publications (3)

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

Buse JB, Bode BW, Mertens A, Cho YM, Christiansen E, Hertz CL, Nielsen MA, Pieber TR; PIONEER 7 investigators. Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabe — View Citation

Pieber TR, Bode B, Mertens A, Cho YM, Christiansen E, Hertz CL, Wallenstein SOR, Buse JB; PIONEER 7 investigators. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 52. 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 52
Secondary	Change in Body Weight	Change from baseline (week 0) in body weight was evaluated at week 52. 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 52
Secondary	Change in HbA1c	Change from baseline (week 0) in HbA1c was evaluated at week 52. 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
Secondary	Change in FPG	Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 52. 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
Secondary	Change in Body Weight (%)	Relative change from baseline (week 0) in body weight (kg) was evaluated at week 52. 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
Secondary	Change in BMI	Change from baseline (week 0) in body mass index (BMI) was evaluated at week 52. 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
Secondary	Change in Waist Circumference	Change from baseline (week 0) in waist circumference was evaluated at week 52. 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
Secondary	Change in Total Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in total cholesterol (mmol/L) at week 52 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 52
Secondary	Change in LDL Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at week 52 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 52
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 52
Secondary	Change in Triglycerides (Ratio to Baseline)	Change from baseline (week 0) in triglycerides (mmol/L) at week 52 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 52
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 week 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.	Week 0, week 52
Secondary	Change in DTSQ	Change from baseline (week 0) in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 52. 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 high blood sugars and low blood sugars, 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 ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.	Week 0, Week 52
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 week 52 is 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 52
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 52 is 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 52
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 week 52 is 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 52
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 week 52 is 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 52
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 week 52 is 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 52
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 52. 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 0-52
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 52. 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 52), 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 0-52
Secondary	Number of TEAEs During Exposure to Trial Product	Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). 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.	Week 0-57
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 0-57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). 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 participant 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.	Week 0-57
Secondary	Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)	Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). 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 participant 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.	Week 0-57
Secondary	Change in Amylase (Ratio to Baseline)	Change from baseline (week 0) in biochemical parameter- amylase (units per liter [U/L]) to week 52 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 52
Secondary	Change in Lipase (Ratio to Baseline)	Change from baseline (week 0) in lipase (U/L) to week 52 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 52
Secondary	Change in Pulse Rate	Change from baseline (week 0) in pulse rate was evaluated at week 52. 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 52
Secondary	Change in Blood Pressure (Systolic and Diastolic Blood Pressure)	Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 52. 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 52
Secondary	Change in HbA1c- Switch	Change from week 52 in HbA1c was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 52, week 104
Secondary	Change in Body Weight- Switch	Change from week 52 in body weight was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 52, week 104
Secondary	Change in Body Weight (%)- Switch	Relative change from week 52 in body weight (kg) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 52, week 104
Secondary	Change in FPG- Switch	Change from week 52 in fasting plasma glucose (FPG) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 52, week 104
Secondary	Change in BMI- Switch	Change from week 52 in body mass index (BMI) was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 52, Week 104
Secondary	Change in Waist Circumference- Switch	Change from week 52 in waist circumference was evaluated at week 104. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 52, week 104
Secondary	Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)- Switch	Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 104. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 104 (i.e., after 52 weeks of treatment in the extension phase)
Secondary	Participants Who Achieve HbA1c =6.5% (48 mmol/Mol) AACE Target (Yes/no)- Switch	Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 104 (i.e., after 52 weeks of treatment in the extension phase)
Secondary	Participants Who Achieve Weight Loss =5% (Yes/no)- Switch	Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 104 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 104 (i.e., after 52 weeks of treatment in the extension phase)
Secondary	Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)- Switch	Participants who achieved HbA1c less than 7.0% without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 104 is 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 re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Week 104 (i.e., after 52 weeks of treatment in the extension phase)
Secondary	Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target and no Need for Rescue Medication (Yes/no)- Switch	Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) and no need for rescue medication (yes/no), was evaluated at week 104. 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.	Week 104 (i.e., after 52 weeks of treatment in the extension phase)
Secondary	Time to Additional Anti-diabetic Medication- Switch	Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the period from week 53 to week 104. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after re-randomisation (week 52) and before (planned) end-of-treatment (week 104), 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 re-randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.	Weeks 53-104
Secondary	Time to Rescue Medication- Switch	Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 53 to week 104. 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 re-randomisation (week 52) 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 53-104
Secondary	Number of TEAEs During Exposure to Trial Product- Switch	Treatment emergent adverse events (TEAEs) were recorded from week 53 to week 109. 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.	Week 53-109
Secondary	Change in Amylase (Ratio to Baseline)- Switch	Change from week 52 in biochemical parameter- amylase (U/L) to week 104 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 52, Week 104
Secondary	Change in Lipase (Ratio to Baseline)- Switch	Change from week 52 in lipase (U/L) to week 104 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 52, Week 104
Secondary	Change in Pulse Rate- Switch	Change from week 52 in pulse rate was evaluated at week 104. 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 52, week 104
Secondary	Change in Blood Pressure (Systolic and Diastolic Blood Pressure)- Switch	Change from week 52 in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 104. 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 52, week 104
Secondary	Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes- Switch	Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 53 to 109. 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 participant 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.	Week 53-109
Secondary	Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)- Switch	Number of participants with treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 53 to 109. 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 participant 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.	Week 53-109
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)- Switch	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 week 52 in the domain scores and component summary (PCS and MCS) scores were evaluated at week 104. A positive change score indicates an improvement since week 52. Results are based on the data from the in-trial observation period.	Week 52, week 104
Secondary	Change in DTSQ- Switch	Change from week 52 in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 104. 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 high blood sugars and low blood sugars, 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 ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.	Week 52, week 104
Secondary	Change in HbA1c- Sustainability	Change from baseline (week 0) in HbA1c was evaluated at week 104. 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 104
Secondary	Change in Body Weight (kg)- Sustainability	Change from baseline (week 0) in body weight was evaluated at week 104. 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.	Week 0, week 104
Secondary	Change in Body Weight (%)- Sustainability	Relative change from baseline (week 0) in body weight (kg) was evaluated at week 104. 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 104
Secondary	Change in FPG- Sustainability	Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 104. 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 104
Secondary	Change in BMI- Sustainability	Change from baseline (week 0) in body mass index (BMI) was evaluated at week 104. 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 104
Secondary	Change in Waist Circumference- Sustainability	Change from baseline (week 0) in waist circumference was evaluated at week 104. 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 104
Secondary	Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)- Sustainability	Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 104. 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.	Week 104
Secondary	Participants Who Achieve HbA1c =6.5% (48 mmol/Mol) AACE Target (Yes/no)- Sustainability	Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 104 is 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 104
Secondary	Participants Who Achieve Weight Loss =5% (Yes/no)- Sustainability	Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 104 is 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 104
Secondary	Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)- Sustainability	Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 104 is 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 104
Secondary	Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target or HbA1c Reduction = 1%-Point (10.9 mmol/Mol) (Yes/no)- Sustainability	Participants who achieved HbA1c <7.0% ADA target or HbA1c reduction = 1%-point (10.9 mmol/mol) (yes/no), was evaluated at week 104. 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.	Week 104
Secondary	Number of TEAEs During Exposure to Trial Product- Sustainability	Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) 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.	Week 0-109
Secondary	Change in Amylase (Ratio to Baseline)- Sustainability	Change from baseline (week 0) in biochemical parameter- amylase (units per liter [U/L]) to week 104 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 104
Secondary	Change in Lipase (Ratio to Baseline)- Sustainability	Change from baseline (week 0) in lipase (U/L) to week 104 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 104
Secondary	Change in Pulse Rate- Sustainability	Change from baseline (week 0) in pulse rate was evaluated at week 104. 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 104
Secondary	Change in Blood Pressure (Systolic and Diastolic Blood Pressure)- Sustainability	Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 104. 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 104
Secondary	Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes)- Sustainability	Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) 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 participant 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.	Week 0-109
Secondary	Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)- Sustainability	Number of participants with treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-109 ((104-week treatment period for participants who continued in the extension phase or 52-week treatment period for participants who did not continue in the extension phase) 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 participant 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.	Week 0-109
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)- Sustainability	Short form (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 104. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.	Week 0, week 104
Secondary	Change in DTSQ- Sustainability	Change from week 0 in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 104. 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 high blood sugars and low blood sugars, 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 ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.	Week 0, week 104

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