A Research Study Comparing a New Medicine Oral Semaglutide to Sitagliptin in People With Type 2 Diabetes (PIONEER 12)

China Multi-regional Clinical Trial: Efficacy and Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus Treated With Metformin

This study compares 2 medicines for type 2 diabetes: oral semaglutide (a new medicine) and sitagliptin (a medicine doctors can already prescribe). Participants will either get oral semaglutide or sitagliptin - which treatment is decided by chance. Participants will get 2 tablets a day to take first thing in the morning on an empty stomach. Only 1 tablet has study medicine in it. The other tablet is a dummy medicine (placebo). After taking the semaglutide tablet, participants may not eat or drink anything for at least 30 minutes. After the 30 minutes, participants must take the sitagliptin tablet. Then participants can have their first meal of the day and take any other medicines they may need, including their metformin. The study will last for about 7 months (33 weeks). Participants will have 8 clinic visits and 1 phone call with the study doctor. At all 8 of the clinic visits, participants will have blood samples taken.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Oral semaglutide; Drug: Placebo (sitagliptin); Drug: Sitagliptin; Drug: Placebo (oral semaglutide)

• Study Type: Interventional
• Enrollment (Actual): 1441
• Phase: Phase 3

Contacts and Locations

Study Locations

• Algeria
  • Algiers, Algeria, 16000
    • Novo Nordisk Investigational Site
  • Algiers, Algeria, 16003
    • Novo Nordisk Investigational Site
• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90430-001
      • Novo Nordisk Investigational Site
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 01228-000
      • Novo Nordisk Investigational Site
    • São Paulo, Sao Paulo, Brazil, 01228-200
      • Novo Nordisk Investigational Site
• China
  • Changsha, China, 410013
    • Novo Nordisk Investigational Site
  • Anhui
    • Hefei, Anhui, China, 230001
      • Novo Nordisk Investigational Site
    • Hefei, Anhui, China, 230061
      • Novo Nordisk Investigational Site
  • Beijing
    • Beijing, Beijing, China, 100044
      • Novo Nordisk Investigational Site
    • Beijing, Beijing, China, 100144
      • Novo Nordisk Investigational Site
    • Beijing, Beijing, China, 101200
      • Novo Nordisk Investigational Site
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • Novo Nordisk Investigational Site
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Novo Nordisk Investigational Site
    • Quanzhou, Fujian, China, 362000
      • Novo Nordisk Investigational Site
  • Guangdong
    • Foshan, Guangdong, China, 528399
      • Novo Nordisk Investigational Site
    • Guangzhou, Guangdong, China, 510120
      • Novo Nordisk Investigational Site
    • Guangzhou, Guangdong, China, 511400
      • Novo Nordisk Investigational Site
    • Huizhou, Guangdong, China, 516001
      • Novo Nordisk Investigational Site
    • Shantou, Guangdong, China, 515065
      • Novo Nordisk Investigational Site
  • Hebei
    • Cangzhou, Hebei, China, 061000
      • Novo Nordisk Investigational Site
    • Hengshui, Hebei, China, 053000
      • Novo Nordisk Investigational Site
    • Shijiazhuang, Hebei, China, 050000
      • Novo Nordisk Investigational Site
  • Henan
    • Kaifeng, Henan, China, 475000
      • Novo Nordisk Investigational Site
    • Luoyang, Henan, China, 471003
      • Novo Nordisk Investigational Site
    • Zhengzhou, Henan, China, 450004
      • Novo Nordisk Investigational Site
  • Hubei
    • Shiyan, Hubei, China, 442008
      • Novo Nordisk Investigational Site
    • Wuhan, Hubei, China, 430034
      • Novo Nordisk Investigational Site
  • Hunan
    • Changsha, Hunan, China, 410018
      • Novo Nordisk Investigational Site
    • Chenzhou, Hunan, China, 423000
      • Novo Nordisk Investigational Site
    • Hengyang, Hunan, China, 421001
      • Novo Nordisk Investigational Site
    • Zhuzhou, Hunan, China, 412007
      • Novo Nordisk Investigational Site
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Novo Nordisk Investigational Site
    • Nanjing, Jiangsu, China, 210011
      • Novo Nordisk Investigational Site
    • Nanjing, Jiangsu, China, 211106
      • Novo Nordisk Investigational Site
    • Nanjing, Jiangsu, China, 211166
      • Novo Nordisk Investigational Site
    • Suzhou, Jiangsu, China, 215004
      • Novo Nordisk Investigational Site
    • Suzhou, Jiangsu, China, 215006
      • Novo Nordisk Investigational Site
    • Wuxi, Jiangsu, China, 214023
      • Novo Nordisk Investigational Site
    • Xuzhou, Jiangsu, China, 221002
      • Novo Nordisk Investigational Site
    • Zhenjiang, Jiangsu, China, 212001
      • Novo Nordisk Investigational Site
  • Jiangxi
    • Pingxiang, Jiangxi, China, 337055
      • Novo Nordisk Investigational Site
  • Jilin
    • Changchun, Jilin, China, 130021
      • Novo Nordisk Investigational Site
    • Changchun, Jilin, China, 130033
      • Novo Nordisk Investigational Site
    • Changchun, Jilin, China, 130041
      • Novo Nordisk Investigational Site
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • Novo Nordisk Investigational Site
  • Qinghai
    • Xining, Qinghai, China, 810007
      • Novo Nordisk Investigational Site
  • Shaanxi
    • Xi'an, Shaanxi, China, 710004
      • Novo Nordisk Investigational Site
  • Shandong
    • Jinan, Shandong, China, 250013
      • Novo Nordisk Investigational Site
    • Qingdao, Shandong, China, 266003
      • Novo Nordisk Investigational Site
    • Weifang, Shandong, China, 261041
      • Novo Nordisk Investigational Site
  • Shanghai
    • Pudong New District, Shanghai, China, 201200
      • Novo Nordisk Investigational Site
    • Shanghai, Shanghai, China, 200240
      • Novo Nordisk Investigational Site
    • Shanghai, Shanghai, China, 200040
      • Novo Nordisk Investigational Site
    • Shanghai, Shanghai, China, 200072
      • Novo Nordisk Investigational Site
    • Shanghai, Shanghai, China, 200065
      • Novo Nordisk Investigational Site
    • Shanghai, Shanghai, China, 200120
      • Novo Nordisk Investigational Site
    • Shanghai, Shanghai, China, 200336
      • Novo Nordisk Investigational Site
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Novo Nordisk Investigational Site
    • Tianjin, Tianjin, China, 300211
      • Novo Nordisk Investigational Site
  • Yunnan
    • Kunming, Yunnan, China, 650101
      • Novo Nordisk Investigational Site
    • Kunming, Yunnan, China, 650032
      • Novo Nordisk Investigational Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Novo Nordisk Investigational Site
• Czechia
  • Brno, Czechia, 63900
    • Novo Nordisk Investigational Site
  • Chrudim, Czechia, 537 01
    • Novo Nordisk Investigational Site
  • Liberec, Czechia, 46001
    • Novo Nordisk Investigational Site
  • Praha, Czechia, 130 00
    • Novo Nordisk Investigational Site
  • Praha 4, Czechia, 140 00
    • Novo Nordisk Investigational Site
• Hong Kong
  • Shatin, New Territories, Hong Kong
    • Novo Nordisk Investigational Site
• Romania
  • Bucharest, Romania, 13682
    • Novo Nordisk Investigational Site
  • Constanta, Romania, 900591
    • Novo Nordisk Investigational Site
  • Oradea, Romania, 410169
    • Novo Nordisk Investigational Site
  • Bihor
    • Oradea, Bihor, Romania, 410025
      • Novo Nordisk Investigational Site
    • Oradea, Bihor, Romania, 410151
      • Novo Nordisk Investigational Site
  • Timis
    • Timisoara, Timis, Romania, 300456
      • Novo Nordisk Investigational Site
• Serbia
  • Belgrade, Serbia, 11000
    • Novo Nordisk Investigational Site
  • Belgrade, Serbia, 11080
    • Novo Nordisk Investigational Site
• South Africa
  • Alberton, South Africa, 1449
    • Novo Nordisk Investigational Site
  • Gauteng
    • Arcadia, Gauteng, South Africa, 0083
      • Novo Nordisk Investigational Site
    • Johannesburg, Gauteng, South Africa, 2001
      • Novo Nordisk Investigational Site
    • Johannesburg, Gauteng, South Africa, 2193
      • Novo Nordisk Investigational Site
    • Johannesburg, Gauteng, South Africa, 1812
      • Novo Nordisk Investigational Site
    • Kempton Park, Gauteng, South Africa, 1619
      • Novo Nordisk Investigational Site
    • Soshanguve, Gauteng, South Africa, 0152
      • Novo Nordisk Investigational Site
  • North West
    • Brits, North West, South Africa, 0250
      • Novo Nordisk Investigational Site
  • Western Cape
    • Kuilsriver, Western Cape, South Africa, 7580
      • Novo Nordisk Investigational Site
    • Paarl, Western Cape, South Africa, 7646
      • Novo Nordisk Investigational Site
• Taiwan
  • Taipei, Taiwan, 100
    • Novo Nordisk Investigational Site
  • Taipei, Taiwan, 112
    • Novo Nordisk Investigational Site
  • Taipei, Taiwan, 114
    • Novo Nordisk Investigational Site
  • Taoyuan city, Taiwan, 333
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

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.

For Algeria only: Male or female, age above or equal to 19 years at the time of signing informed consent.

For Taiwan only: Male or female, age above or equal to 20 years at the time of signing informed consent

• Diagnosed with type 2 diabetes mellitus 60 days or more prior to day of screening.
• HbA1c between 7.0-10.5% (53-91 mmol/mol) (both inclusive).
• Stable daily dose of metformin (equal to or above 1500 mg or maximum tolerated dose as documented in the subject medical record) 60 days or more prior to 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 a highly effective contraceptive method (adequate contraceptive measure as required by local regulation or practice).
• Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC). Family is defined as a first degree relative.
• History or presence 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, hospitalization 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 (NYHA) Class IV.
• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening.
• Renal impairment measured as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI).
• Subjects with alanine aminotransferase (ALT) above 2.5 x upper limit of the normal (ULN).
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation. Fundus examination without dilation is only allowed if the digital camera used for fundus photography has this feature.
• Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral semaglutide 3 mg and placebo (sitagliptin); Oral semaglutide tablets 3 mg and sitagliptin placebo tablets for 26 weeks	Drug: Oral semaglutide; Oral semaglutide to be taken every morning in a fasting state, to be followed by sitagliptin placebo after 30 minutes. Only then participants can have their first meal of the day and their pre-study metformin tablets; Drug: Placebo (sitagliptin); Placebo tablet to be taken 30 minutes after oral semaglutide
Experimental: Oral semaglutide 7 mg and placebo (sitagliptin); Oral semaglutide tablets and sitagliptin placebo tablets. The dose of oral semaglutide will be escalated over 4 weeks, after which the target dose of 7 mg is taken for 22 weeks	Drug: Oral semaglutide; Oral semaglutide to be taken every morning in a fasting state, to be followed by sitagliptin placebo after 30 minutes. Only then participants can have their first meal of the day and their pre-study metformin tablets; Drug: Placebo (sitagliptin); Placebo tablet to be taken 30 minutes after oral semaglutide
Experimental: Oral semaglutide 14 mg and placebo (sitagliptin); Oral semaglutide tablets and sitagliptin placebo tablets. The dose of oral semaglutide will be escalated over 8 weeks, after which the target dose of 14 mg is taken for 18 weeks	Drug: Oral semaglutide; Oral semaglutide to be taken every morning in a fasting state, to be followed by sitagliptin placebo after 30 minutes. Only then participants can have their first meal of the day and their pre-study metformin tablets; Drug: Placebo (sitagliptin); Placebo tablet to be taken 30 minutes after oral semaglutide
Experimental: Sitagliptin 100 mg and placebo (oral semaglutide); Sitagliptin tablets and oral semaglutide placebo tablets for 26 weeks	Drug: Sitagliptin; Sitagliptin to be taken every morning, 30 minutes after taking the oral semaglutide placebo tablet. Then participants can have their first meal of the day and their pre-study metformin tablets; Drug: Placebo (oral semaglutide); Placebo tablet to be taken first thing in the morning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 26 in Glycated Haemoglobin (HbA1c) (%)	Change in HbA1c from baseline to week 26 in percentage (%) point of HbA1c is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period and in-trial observation period. On-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication. In-trial observation period: the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication.	From baseline to week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 26 in Fasting Plasma Glucose (FPG)	Change in fasting plasma glucose (FPG) from baseline to week 26 in millimole per liter (mmol/l) is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Change From Baseline to Week 26 in Self-measured Plasma Glucose (SMPG) Profile: Mean 7-point Profile	Change from baseline in mean 7-point SMPG profile at week 26 is presented. 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. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Change From Baseline to Week 26 in 7 Point SMPG Profile: Mean Postprandial Increment (Over All Meals)	Change from baseline in 7-point SMPG: Mean postprandial increment (over all meals) at week 26 is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Number of Participants Who Achieved HbA1c <7.0 % (53 mmol/Mol) (American Diabetes Association [ADA] Target) (Yes/no)	Number of participants who achieved HbA1c <7.0% (53 mmol/mol) (ADA target) is presented in category "Yes" and participants who could not achieve HbA1C <7.0 (53 mmol/mol) (ADA target) is presented in category "No". The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	At week 26
Number of Participants Who Achieved HbA1c Equal to or Below 6.5 Percent (48 mmol/Mol) (American Association of Clinical Endocrinologists (AACE) Target) (Yes/no)	Number of participants who achieved HbA1c equal to or below 6.5 percent (48 mmol/mol) (AACE target) (yes/no) is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	At week 26
Number of Participants Who Achieved HbA1c Reduction Equal to or Above 1 Percent-point (10.9 mmol/Mol) (Yes/no)	Number of participants who achieved HbA1c reduction equal to or above 1 percent-point (10.9 mmol/mol) (yes/no) is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	At week 26
Time to Rescue Medication	Time to rescue medication is presented as the number of participants who had taken rescue medication anytime from baseline to week 31. 'Rescue medication': use of new anti-diabetic medication as add-on to trial product and used for more than 21 days with the initiation at or after randomisation 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. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 31
Change From Baseline to Week 26 in Body Weight (Kilogram [kg])	Change in body weight from baseline to week 26 in kg is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Percentage Change From Baseline to Week 26 in Body Weight	Percentage change from baseline to week 26 in body weight is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Change From Baseline to Week 26 in Body Mass Index (BMI)	Change from baseline in BMI is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Change From Baseline to Week 26 in Waist Circumference	Change from baseline in waist circumference is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Change From Baseline to Week 26 in Fasting Lipid Profile: Total Cholesterol (Ratio to Baseline)	Change from baseline in total cholesterol (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Change From Baseline to Week 26 in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol (Ratio to Baseline)	Change from baseline in LDL cholesterol (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Change From Baseline to Week 26 in Fasting Lipid Profile: Very-low-density Lipoprotein (VLDL) Cholesterol (Ratio to Baseline)	Change from baseline in VLDL cholesterol (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Change From Baseline to Week 26 in Fasting Lipid Profile: High-density Lipoprotein (HDL) Cholesterol (Ratio to Baseline)	Change from baseline in HDL Cholesterol (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Change From Baseline to Week 26 in Fasting Lipid Profile: Triglycerides (Ratio to Baseline)	Change from baseline in triglycerides (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Change From Baseline to Week 26 in Fasting Lipid Profile: Free Fatty Acids (Ratio to Baseline)	Change from baseline in free fatty acids (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey	SF-36 v2.0 is a 36-item, patient-reported survey of patient health. SF-36 measures the participant's overall Health Related Quality of Life on 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) and two component summary scores (physical component summary and mental component summary). Range of score for domains and component summary scores : 1-100 (Higher scores indicated a better health state). A positive change score indicates an improvement since baseline. Outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to end date which was first date of any of following: the last dose of trial product plus 3 days or initiation of rescue medication.	From baseline to week 26
Number of Participants Who Achieved Body Weight Loss Equal to or Above 3 Percent (Yes/no)	Number of participants who achieved body weight loss equal to or above 3 percent (yes/no) is presented. The outcome data was evaluated based on In-trial observation period: This observation period represented the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication. The in-trial observation period started at randomisation (as registered in the IWRS) and ended at the date of: The last direct participant-site contact, which was scheduled to take place 5 weeks after planned last dose of trial product at the follow-up visit; withdrawal for participants who withdrew their informed consent; The last participant-investigator contact as defined by the investigator for participants who were lost to follow-up; Death for participants who died before any of the above.	At week 26
Number of Participants Who Achieved Body Weight Loss Equal to or Above 5 Percent (Yes/no)	Number of participants who achieved body weight loss equal to or above 5 percent (yes/no) is presented. The outcome data was evaluated based on In-trial observation period: This observation period represented the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication. The in-trial observation period started at randomisation (as registered in the IWRS) and ended at the date of: The last direct participant-site contact, which was scheduled to take place 5 weeks after planned last dose of trial product at the follow-up visit; withdrawal for participants who withdrew their informed consent; The last participant-investigator contact as defined by the investigator for participants who were lost to follow-up; Death for participants who died before any of the above.	At week 26
Number of Participants Who Achieved Body Weight Loss Equal to or Above 10 Percent (Yes/no)	Number of participants who achieved body weight loss equal to or above 10 percent (yes/no). The outcome data was evaluated based on In-trial observation period: This observation period represented the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication. The in-trial observation period started at randomisation (as registered in the IWRS) and ended at the date of: The last direct participant-site contact, which was scheduled to take place 5 weeks after planned last dose of trial product at the follow-up visit; withdrawal for participants who withdrew their informed consent; The last participant-investigator contact as defined by the investigator for participants who were lost to follow-up; Death for participants who died before any of the above.	At week 26
Number of Participants Who Achieved HbA1c Below 7.0 Percent (53 mmol/Mol) Without Hypoglycaemia (Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes) and no Body Weight Gain (Yes/no)	Number of participants who achieved HbA1c < 7.0 percent (53 mmol/mol) without hypoglycaemia (treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes) and no body weight gain (yes/no) at week 26 is presented. The outcome data was evaluated based on In-trial observation period: This observation period represented the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication. The in-trial observation period started at randomisation (as registered in the IWRS) and ended at the date of: The last direct participant-site contact, which was scheduled to take place 5 weeks after planned last dose of trial product at the follow-up visit; withdrawal for participants who withdrew their informed consent; The last participant-investigator contact as defined by the investigator for participants who were lost to follow-up; Death for participants who died before any of the above.	At week 26
Number of Participants Who Achieved HbA1c Reduction Equal to or Above 1 Percent-point (10.9 mmol/Mol) and Body Weight Loss Equal to or Above 3 Percent (Yes/no)	Number of participants who achieved HbA1c reduction equal to or above 1 percent-point (10.9 mmol/mol) and body weight loss equal to or above 3 percent (yes/no) is presented. The outcome data was evaluated based on In-trial observation period: This observation period represented the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication. The in-trial observation period started at randomisation (as registered in the IWRS) and ended at the date of: The last direct participant-site contact, which was scheduled to take place 5 weeks after planned last dose of trial product at the follow-up visit; withdrawal for participants who withdrew their informed consent; The last participant-investigator contact as defined by the investigator for participants who were lost to follow-up; Death for participants who died before any of the above.	At week 26
Number of Treatment-emergent Adverse Events During Exposure to Trial Product	An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. AEs with onset during the on-treatment period correspond to treatment-emergent AEs (TEAEs). The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 31
Number of Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product	Number of treatment-emergent severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes during exposure to trial product is presented. Severe: requiring assistance from another person for recovery. 'BG-confirmed': hypoglycaemic episode with a plasma glucose value < 3.1 mmol/L (56 mg/dL); The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 31
Change From Baseline to Week 26 in Haematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils	Change from baseline in hematology parameters such as basophils, eosinophils, lymphocytes, monocytes, and neutrophils were reported. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Haematology Parameter: Haematocrit (Ratio to Baseline)	Change from baseline in Haematocrit at week 26 is reported as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Haematology Parameter: Haemoglobin (Ratio to Baseline)	Change from baseline in Haemoglobin at week 26 is reported as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Haematology Parameter: Leucocytes (Ratio to Baseline)	Change from baseline in Leucocytes at week 26 is reported as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Haematology Parameter: Thrombocytes (Ratio to Baseline)	Change from baseline in thrombocytes at week 26 is reported as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Biochemistry Parameter: Calcium (Total) (Ratio to Baseline)	Change from baseline in calcium (total) (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Biochemistry Parameter: Potassium (Ratio to Baseline)	Change from baseline in potassium (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Biochemistry Parameter: Sodium (Ratio to Baseline)	Change from baseline in sodium (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Biochemistry Parameter: Urea (Ratio to Baseline)	Change from baseline in urea (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Biochemistry Parameter: Albumin (Ratio to Baseline)	Change from baseline in Albumin (measured in grams per deciliter [g/dL]) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Calcitonin (Ratio to Baseline)	Change from baseline in calcitonin (measured in picograms per milliliter [pg/ml]) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Vital Signs: Pulse Rate	Change from baseline in pulse rate is presented. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Vital Signs: Systolic Blood Pressure	Change from baseline in systolic blood pressure is presented. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Vital Signs: Diastolic Blood Pressure	Change from baseline in diastolic blood pressure is presented. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Change From Baseline to Week 26 in Electrocardiogram (ECG) Category	Change from baseline in ECG category at week 26 is presented. Change from baseline results are presented as shift in findings categorized as: normal, abnormal and not clinically significant (NCS), and abnormal and clinically significant (CS). The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Physical Examination Category	The physical examination values for different body systems at baseline and week 26 are presented. The investigator interpreted the results and categorised them as: normal, abnormal NCS or abnormal CS. The physical examination are presented for the following body systems: cardiovascular system; central and peripheral nervous system; gastrointestinal system, including mouth; general appearance; head, ears, eyes, nose, throat, neck; lymph node palpation; musculoskeletal system; respiratory system; skin; and thyroid gland. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	Baseline and week 26
Change From Baseline to Week 26 in Eye Examination Category	The eye examination category at baseline and week 26 are presented. The investigator interpreted the results and categorised them as: normal, abnormal NCS or abnormal CS. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 26
Number of Participants With Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product	Number of participants with treatment-emergent severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes during exposure to trial product is presented. Severe: requiring assistance from another person for recovery. 'BG-confirmed': hypoglycaemic episode with a plasma glucose value < 3.1 mmol/L (56 mg/dL); The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.	From baseline to week 31

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2019
• Primary Completion (Actual): October 27, 2021
• Study Completion (Actual): October 27, 2021

Study Registration Dates

• First Submitted: July 11, 2019
• First Submitted That Met QC Criteria: July 11, 2019
• First Posted (Actual): July 12, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 28, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: NN9924-4309; U1111-1188-1256 (Other Identifier: World Health Organization (WHO)); 2018-002589-38 (Registry Identifier: European Medicines Agency (EudraCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No