A Research Study Comparing a New Medicine Oral Semaglutide to Placebo in People With Type 2 Diabetes (PIONEER 11)

China Multi-regional Clinical Trial: Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Diet and Exercise Only

The study compares 2 medicines for type 2 diabetes: oral semaglutide (a new medicine) and placebo (a dummy medicine). Researchers will test semaglutide to see how well it works compared to placebo. The study will also test if semaglutide is safe. Participants will either get semaglutide or placebo - which treatment is decided by chance. Participants will get 1 tablet a day to take with up to half a glass of water. Participants must take the tablet first thing in the morning on an empty stomach. After taking the tablet, participants must not eat or drink anything for at least 30 minutes. After the 30 minutes, participants can have their first meal of the day and take any other medicines they may need. The study will last for about 8 months (36 weeks). Participants will have 9 clinic visits and 2 phone calls with the study doctor. At all 9 of the clinic visits, participants will have blood samples taken. At 5 of the clinic visits, participants must arrive fasting. This means they cannot eat for 8 hours before the visit. It is fine to drink water up to 2 hours before the visit. This is for some of the blood samples that will be taken at the visit. Women cannot take part if pregnant, breastfeeding or planning to become pregnant during the study period.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Oral semaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 521
• Phase: Phase 3

Contacts and Locations

Study Locations

• Algeria
  • Algiers, Algeria, 16000
    • Novo Nordisk Investigational Site
  • Algiers, Algeria, 16049
    • Novo Nordisk Investigational Site
• China
  • Changsha, China, 410013
    • Novo Nordisk Investigational Site
  • Anhui
    • Hefei, Anhui, China, 230061
      • Novo Nordisk Investigational Site
  • Beijing
    • Beijing, Beijing, China, 101200
      • Novo Nordisk Investigational Site
    • Beijing, Beijing, China, 102218
      • Novo Nordisk Investigational Site
  • Chongqing
    • ChongQing, Chongqing, China, 404000
      • Novo Nordisk Investigational Site
    • Chongqing, Chongqing, China, 400010
      • Novo Nordisk Investigational Site
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Novo Nordisk Investigational Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Novo Nordisk Investigational Site
    • Guangzhou, Guangdong, China, 510150
      • 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
    • Handan, Hebei, China, 056002
      • Novo Nordisk Investigational Site
    • Hengshui, Hebei, China, 053000
      • Novo Nordisk Investigational Site
    • Shijiazhuang, Hebei, China, 050000
      • Novo Nordisk Investigational Site
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Novo Nordisk Investigational Site
  • Hubei
    • Shiyan, Hubei, China, 442008
      • Novo Nordisk Investigational Site
  • Hunan
    • Changde, Hunan, China, 415003
      • Novo Nordisk Investigational Site
    • Chenzhou, Hunan, China, 423000
      • Novo Nordisk Investigational Site
    • Yueyang, Hunan, China, 414000
      • Novo Nordisk Investigational Site
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Novo Nordisk Investigational Site
    • Huai'an, Jiangsu, China, 223002
      • Novo Nordisk Investigational Site
    • Nanjing, Jiangsu, China, 210011
      • Novo Nordisk Investigational Site
    • Nanjing, Jiangsu, China, 211106
      • 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
    • Jiaxing, Jiangxi, China, 314001
      • Novo Nordisk Investigational Site
    • Nanchang, Jiangxi, China, 330006
      • 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, 810001
      • Novo Nordisk Investigational Site
  • Shaanxi
    • Xi'an, Shaanxi, China, 710004
      • Novo Nordisk Investigational Site
  • Shandong
    • Jinan, Shandong, China, 250013
      • Novo Nordisk Investigational Site
    • Jining, Shandong, China, 272029
      • Novo Nordisk Investigational Site
    • Qingdao, Shandong, China, 266003
      • 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, 200072
      • Novo Nordisk Investigational Site
    • Shanghai, Shanghai, China, 200065
      • Novo Nordisk Investigational Site
    • Shanghai, Shanghai, China, 200336
      • Novo Nordisk Investigational Site
    • Shanghai, Shanghai, China, 200025
      • Novo Nordisk Investigational Site
  • Sichuan
    • Chengdu, Sichuan, China, 610071
      • Novo Nordisk Investigational Site
  • Tianjin
    • Tianjin, Tianjin, China, 300211
      • Novo Nordisk Investigational Site
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • Novo Nordisk Investigational Site
• Hungary
  • Budapest, Hungary, 1032
    • Novo Nordisk Investigational Site
  • Nagykanizsa, Hungary, 8800
    • Novo Nordisk Investigational Site
  • Tatabánya, Hungary, 2800
    • Novo Nordisk Investigational Site
  • Zalaegerszeg, Hungary, 8900
    • Novo Nordisk Investigational Site
• Serbia
  • Belgrade, Serbia, 11080
    • Novo Nordisk Investigational Site
  • Nis, Serbia, 18000
    • Novo Nordisk Investigational Site
• Taiwan
  • Taipei, Taiwan, 100
    • Novo Nordisk Investigational Site
  • Taipei, Taiwan, 112
    • Novo Nordisk Investigational Site
  • Taoyuan city, Taiwan, 333
    • Novo Nordisk Investigational Site
• Ukraine
  • Dnipro, Ukraine, 49038
    • Novo Nordisk Investigational Site
  • Khmelnytskyi, Ukraine, 29000
    • Novo Nordisk Investigational Site
  • Kyiv, Ukraine, 04114
    • Novo Nordisk Investigational Site
  • Mykolaiv, Ukraine, 54003
    • Novo Nordisk Investigational Site
  • Poltava, Ukraine, 36039
    • Novo Nordisk Investigational Site
  • Ternopil, Ukraine, 46002
    • Novo Nordisk Investigational Site
  • Zaporizhia, Ukraine, 69600
    • 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 the informed consent.

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

• Diagnosed with type 2 diabetes mellitus
• HbA1c between 7.0 -10.0% (53-86 mmol/mol) (both inclusive).

Exclusion Criteria:

• - Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an highly effective contraceptive method.
• 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.
• 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).
• 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 3mg; Subjects will remain on 3 mg for the entire treatment period (26 weeks)	Drug: Oral semaglutide; Tablets to be taken once-daily for 26 weeks
Experimental: Oral semaglutide 7mg; Subjects will receive 3 mg for for the first 4 weeks, 7 mg for the remainder of the treatment period	Drug: Oral semaglutide; Tablets to be taken once-daily for 26 weeks
Experimental: Oral semaglutide 14mg; Subjects will receive 3 mg for the first 4 weeks, 7 mg for the next 4 weeks and 14 mg for the remainder of the treatment period	Drug: Oral semaglutide; Tablets to be taken once-daily for 26 weeks
Placebo Comparator: Placebo (oral semaglutide); Subjects will receive placebo tablets for the entire treatment period	Drug: Placebo; Tablets to be taken once-daily for 26 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glycosylated Haemoglobin (HbA1c)	Change from baseline (week 0) in HbA1c 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 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.	Baseline (Week 0), Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Body Weight (Kilograms [kg])	Change from baseline (week 0) in body weight 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 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.	Baseline (Week 0), Week 26
Change From Baseline in Fasting Plasma Glucose (FPG)	Change from baseline (week 0) in FPG 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 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.	Baseline (Week 0), Week 26
Change From Baseline in Fasting 7-point Self-measured Plasma Glucose (SMPG) Profile: Mean 7-point Profile	Change from baseline (week 0) 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 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.	Baseline (Week 0), Week 26
Change From Baseline in Fasting 7-point Self-measured Plasma Glucose Profile: Mean Postprandial Increment (Over All Meals)	Change from baseline (week 0) in fasting 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 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.	Baseline (Week 0), Week 26
Change From Baseline in Body Weight (Percentage [%])	Change from baseline (week 0) in body weight (measured in kg) 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 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.	Baseline (Week 0), Week 26
Change From Baseline in Body Mass Index (BMI)	Change from baseline (week 0) in BMI 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 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.	Baseline (Week 0), Week 26
Change From Baseline in Waist Circumference	Change from baseline (week 0) in waist circumference 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 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.	Baseline (Week 0), Week 26
Change From Baseline in Fasting Lipid Profile: Total Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in total cholesterol (measured in mg/dL) 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.	Baseline (Week 0), Week 26
Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in LDL cholesterol (measured in mg/dL) 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.	Baseline (Week 0), Week 26
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) Cholesterol (Ratio to Baseline)	Change from baseline (week 0) in HDL cholesterol (measured in mg/dL) 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.	Baseline (Week 0), Week 26
Change From Baseline in Fasting Lipid Profile: Triglycerides (Ratio to Baseline)	Change from baseline (week 0) in triglycerides (measured in mg/dL) 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.	Baseline (Week 0), Week 26
Change From Baseline 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). Change form baseline in each domain, physical component summary score and mental component summary score at week 26 is presented. A positive change score indicates an improvement since 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.	Baseline (Week 0), Week 26
Number of Participants Who Achieved HbA1c Less Than (<) 7.0 % (53 Millimoles Per Mole [mmol/Mol]) (American Diabetes Association (ADA) Target) (Yes/no)	Number of participants who achieved HbA1c < 7.0 % (53 mmol/mol) (ADA target) 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 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.	Week 26
Number of Participants Who Achieved HbA1c Less Than or Equal to (<=) 6.5 Percent (48 mmol/Mol) (American Association of Clinical Endocrinologists (AACE) Target) (Yes/no)	Number of participants who achieved HbA1c <= 6.5 percent (48 mmol/mol) (AACE target) 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 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.	Week 26
Number of Participants Who Achieved HbA1c Reduction Greater Than or Equal to (>=) 1 Percent (10.9 mmol/Mol) (Yes/no)	Number of participants who achieved HbA1c reduction >= 1 percent (10.9 mmol/mol) 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 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.	Week 26
Number of Participants Who Achieved Body Weight Loss >= 3 Percent (Yes/no)	Number of participants who achieved body weight loss >= 3 percent (yes/no) 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 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.	Week 26
Number of Participants Who Achieved Body Weight Loss >= 5 Percent (Yes/no)	Number of participants who achieved body weight loss >= 5 percent (yes/no) 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 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.	Week 26
Number of Participants Who Achieved Body Weight Loss >= 10 Percent (Yes/no)	Number of participants who achieved body weight loss >= 10 percent (yes/no) 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 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.	Week 26
Number of Participants Who Achieved HbA1c < 7.0 Percent (53 mmol/Mol) Without Hypoglycaemia (Treatment-emergent Severe or Blood Glucose [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 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.	Week 26
Number of Participants Who Achieved HbA1c Reduction >= 1% (10.9 mmol/Mol) and Body Weight Loss >= 3 Percent (Yes/no)	Number of participants who achieved HbA1c reduction >= 1% (10.9 mmol/mol) and body weight loss >= 3% (yes/no) 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 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.	Week 26
Time From First Dose to Initiation of Rescue Medication	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 randomization 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 randomization 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 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 (Week 0) to Week 26
Semaglutide Plasma Concentrations	Semaglutide plasma concentrations 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 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.	Week 26: post dose any time
Change From Baseline in Haematology - Haematocrit (Ratio to Baseline)	Change from baseline (week 0) in haematocrit (measured in %) 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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Haematology - Haemoglobin (Ratio to Baseline)	Change from baseline (week 0) in haemoglobin (measured in millimoles per liter [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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Haematology - Leucocytes (Ratio to Baseline)	Change from baseline (week 0) in leucocytes (measured in 10^9 per liter [10^9/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Haematology - Thrombocytes (Ratio to Baseline)	Change from baseline (week 0) in thrombocytes (measured in 10^9/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Haematology - Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils	Change from baseline (week 0) in basophils, eosinophils, lymphocytes, monocytes and neutrophils at week 26 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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Biochemistry - Urea (Ratio to Baseline)	Change from baseline (week 0) 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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Biochemistry - Creatinine (Ratio to Baseline)	Change from baseline (week 0) in creatinine (measured in mg/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Biochemistry - Alanine Aminotransferase (Ratio to Baseline)	Change from baseline (week 0) in alanine aminotransferase (measured in units per liter [U/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Biochemistry - Aspartate Aminotransferase (Ratio to Baseline)	Change from baseline (week 0) in aspartate aminotransferase (measured in U/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Biochemistry - Alkaline Phosphatase (Ratio to Baseline)	Change from baseline (week 0) in alkaline phosphatase (measured in U/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Biochemistry - Total Bilirubin (Ratio to Baseline)	Change from baseline (week 0) in total bilirubin (measured in mg/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Biochemistry - Amylase (Ratio to Baseline)	Change from baseline (week 0) in amylase (measured in U/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Biochemistry - Lipase (Ratio to Baseline)	Change from baseline (week 0) in lipase (measured in U/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Biochemistry - Creatine Kinase (Ratio to Baseline)	Change from baseline (week 0) in creatine kinase (measured in U/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Calcium (Ratio to Baseline)	Change from baseline (week 0) in calcium (measured in mg/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Potassium (Ratio to Baseline)	Change from baseline (week 0) in potassium (measured in milliequivalents per liter [mEq/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Sodium (Ratio to Baseline)	Change from baseline (week 0) in sodium (measured in mEq/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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Albumin (Ratio to Baseline)	Change from baseline (week 0) in albumin (measured in 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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Calcitonin (Ratio to Baseline)	Change from baseline (week 0) 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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Pulse Rate	Change from baseline (week 0) in pulse rate at week 26 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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Systolic Blood Pressure	Change from baseline (week 0) in systolic blood pressure at week 26 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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Diastolic Blood Pressure	Change from baseline (week 0) in diastolic blood pressure at week 26 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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Electrocardiogram (ECG) Category	Change from baseline (week 0) 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, follow-up prematurely discontinuation visit, last dose of trial product plus 38 days or the end-date for the in-trial observation period.	Baseline (Week 0), Week 26
Change From Baseline in Physical Examination Category	Change from baseline (week 0) in physical examination category at week 26 is presented. The physical examination shift in findings were categorized as normal, abnormal NCS and abnormal CS and 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 last date on trial product plus 3 days.	Baseline (Week 0), Week 26
Change From Baseline in Eye Examination Category	Change from baseline (week 0) in eye examination category at week 26 is presented. Eye examination shift in findings were categorized as normal, abnormal NCS and 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, follow-up prematurely discontinuation visit, last date on trial product plus 38 days or the end-date for the in-trial observation period.	Baseline (Week 0), Week 26
Number of Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. An AE can therefore be 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. TEAE was defined as an AE with onset in the on-treatment observation period. 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, follow-up prematurely discontinuation visit, last date on trial product plus 38 days or the end-date for the in-trial observation period.	Up to 31 weeks
Number of Treatment-emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes	Severe or BG confirmed symptomatic hypoglycaemia was defined as an episode that was severe according to the ADA classification or BG confirmed by a plasma glucose (PG) value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. 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, follow-up prematurely discontinuation visit, last date on trial product plus 38 days or the end-date for the in-trial observation period.	Up to 31 weeks
Number of Participants With Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes	Severe or BG confirmed symptomatic hypoglycaemia was defined as an episode that was severe according to the ADA classification or BG confirmed by a plasma glucose (PG) value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. 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, follow-up prematurely discontinuation visit, last date on trial product plus 38 days or the end-date for the in-trial observation period.	Up to 31 weeks
Anti-semaglutide Binding Antibody Levels	Anti-semaglutide binding antibody levels measured anytime during post-baseline visits (week 0 to week 31) are presented. The outcome data are presented as percentage of bound radioactivity-labelled semaglutide/total added radioactivity-labelled semaglutide (%B/T). Results are based on the data from the in-trial observation period - the in-trial observation period started at randomization and ended at the date of: the last direct participant-site contact, withdrawal for participants who withdrew their informed consent, the last participant-investigator contact, and death for participants who died before any of the above.	Up to 31 weeks
Number of Participants With Anti-semaglutide Binding Antibodies	Number of participants who had anti-semaglutide binding antibody levels anytime during post-baseline visits (week 0 to week 31) are presented. Results are based on the data from the in-trial observation period - the in-trial observation period started at randomization and ended at the date of: the last direct participant-site contact, withdrawal for participants who withdrew their informed consent, the last participants-investigator contact, and death for participants who died before any of the above.	Up to 31 weeks
Number of Participants With Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1	Number of participants who had anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) anytime during post-baseline visits (week 0 to week 31) are presented. Results are based on the data from the in-trial observation period - the in-trial observation period started at randomization and ended at the date of: the last direct participant-site contact, withdrawal for participants who withdrew their informed consent, the last participant-investigator contact, and death for participants who died before any of the above.	Up to 31 weeks

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): October 1, 2019
• Primary Completion (Actual): September 23, 2021
• Study Completion (Actual): October 27, 2021

Study Registration Dates

• First Submitted: September 27, 2019
• First Submitted That Met QC Criteria: September 27, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 4, 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
• Other Study ID Numbers: NN9924-4338; U1111-1188-1173 (Other Identifier: World Health Organization (WHO)); 2018-002590-22 (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