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Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes (PIONEER 3)

Primary Purpose

Diabetes, Diabetes Mellitus, Type 2

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

semaglutide

sitagliptin

placebo

About this trial

This is an interventional treatment trial for Diabetes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female, age at least 18 years at the time of signing informed consent For Japan only: Male or female, age at least 20 years at the time of signing informed consent
Diagnosed with T2DM (type 2 diabetes mellitus) for at least 90 days prior to day of screening
HbA1c (glycosylated haemoglobin) 7.0-10.5 % (53-91 mmol/mol) (both inclusive).
Stable daily dose of metformin (equal or above 1500 mg or maximum tolerated dose as documented in subject medical record) alone or in combination with SU (= half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record) within 90 days prior to the day of screening

Exclusion Criteria:

Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice). For certain specific countries: Additional specific requirements apply
Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN 2) or Medullary Thyroid Carcinoma (MTC)
History of pancreatitis (acute or chronic)
History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
Any of the following: myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischaemic attack within the past 180 days prior to the day of screening
Subjects presently classified as being in New York Heart Association (NYHA) Class IV.
Planned coronary, carotid or peripheral artery revascularisation known on the day of screening.
Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinomas)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

Semaglutide 3 mg

Semaglutide 7 mg

Semaglutide 14 mg

Sitagliptin 100 mg

Arm Description

Outcomes

Primary Outcome Measures

Change in HbA1c: Week 26

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Secondary Outcome Measures

Change in Body Weight: Week 26

Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Change in HbA1c: Weeks 52 and 78

Change from baseline (week 0) in HbA1c was evaluated at weeks 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Body Weight (kg): Weeks 52 and 78

Change from baseline (week 0) in body weight was evaluated at weeks 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Body Weight (%)

Relative change from baseline (week 0) in body weight (kg) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in FPG

Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in BMI

Change from baseline (week 0) in body mass index (BMI) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Waist Circumference

Change from baseline (week 0) in waist circumference was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Total Cholesterol (Ratio to Baseline)

Change from baseline (week 0) in total cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in LDL Cholesterol (Ratio to Baseline)

Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in VLDL Cholesterol (Ratio to Baseline)

Change from baseline (week 0) in very-low-density lipoprotein (VLDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

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.

Change in Triglycerides (Ratio to Baseline)

Change from baseline (week 0) in triglycerides (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Free Fatty Acids (Ratio to Baseline)

Change from baseline (week 0) in free fatty acids (FFA) (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Because of an issue with the handling of the blood samples for FFA, all FFA data were considered invalid for this trial; thus, no conclusion with regards to FFA levels can be made based on the data presented here.

Change in SMPG - Mean 7-point Profile

Change from baseline (week 0) in mean 7-point self-measured plasma glucose (SMPG) profile. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in SMPG - Mean Postprandial Increment Over All Meals

Change from baseline (week 0) in the average of the post-prandial increments over all meals was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)

Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)

Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve Weight Loss ≥5% (Yes/no)

Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve Weight Loss ≥10% (Yes/no)

Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)

Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at weeks 26, 52 and 78 are presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time to Additional Anti-diabetic Medication

Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26, week 0 to week 52 and week 0 to week 78. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 78), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time to Rescue Medication

Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26, week 0 to week 52 and week 0 to week 78. Rescue medication was defined as any new anti-diabetic medication used as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Number of TEAEs During Exposure to Trial Product

Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 83 (78-week treatment period plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Amylase (Ratio to Baseline)

Change from baseline (week 0) in amylase (units/litre (U/L)) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Lipase (Ratio to Baseline)

Change from baseline (week 0) in lipase (U/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in Pulse Rate

Change from baseline (week 0) in pulse rate was evaluated at weeks 26, 52 and 78. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in SBP and DBP

Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at weeks 26, 52 and 78. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in ECG Evaluation

Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at weeks 26, 52 and 78. Change from baseline results are presented as shift in findings (normal, abnormal and not clinically significant (NCS) and abnormal and clinically significant (CS)) from week 0 to week 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in Physical Examination

Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (weeks -2), weeks 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system; 2) Central and peripheral nervous system; 3) Gastrointestinal system, incl. mouth; 4) General appearance; 5) Head, ears, eyes, nose, throat, neck; 6) Lymph node palpation; 7) Musculoskeletal system; 8) Respiratory system; 9) Skin; 10) Thyroid gland.

Change in Eye Examination Category

Participants with eye examination (fundoscopy) findings, normal, abnormal NCS and abnormal CS at baseline (week -2), week 52 and week 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)

This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide binding antibodies anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)

This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide neutralising antibodies anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no)

This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)

This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide neutralising antibodies cross reacting with native GLP-1 anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Anti-semaglutide Binding Antibody Levels

This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). It is based on the data from participants who were measured with anti-semaglutide antibodies anytime during post-baseline visits (weeks 0-83). Results are presented as percentage of bound radioactivity-labelled semaglutide /total added radioactivity-labelled semaglutide (%B/T). Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-83 (78-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded from week 0 to week 83 (78-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Semaglutide Plasma Concentration in a Subset of the Participants for Population PK Analyses

This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Semaglutide plasma concentrations for participants in the pharmacokinetic (PK) subpopulation are presented. The PK subpopulation consisted of participants from sites in Germany, Japan and the United States receiving oral semaglutide (3 mg, 7 mg or 14 mg). Results are based on the data from the on-treatment observation period and follow-up period. The on-treatment observation period was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)

SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 26, 52 and 78. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.

Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains

The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. The items of the IWQOL-Lite-CT pertain to physical functioning (physical, physical function and pain/discomfort) and psychosocial domains and all items employ a 5-point graded response scale (never, rarely, sometimes, usually, always; or not at all true, a little true, moderately true, mostly true, completely true). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Change in CoEQ: Scores From the 4 Domains and the 19 Items

Change from baseline (week 0) in Control of Eating Questionnaire (CoEQ) was evaluated at weeks (wk) 26, 52 and 78. The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control' (items 9-12, 19), 'positive mood' (items 5-8), 'craving for savoury' (items 4, 16-18) and 'craving for sweet' (items 3, 13-15). The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the data from the in-trial observation period.

Full Information

NCT ID

NCT02607865

First Posted

November 10, 2015

Last Updated

July 11, 2022

Sponsor

Novo Nordisk A/S

1. Study Identification

Unique Protocol Identification Number

NCT02607865

Brief Title

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

Acronym

PIONEER 3

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

February 15, 2016 (Actual)

Primary Completion Date

February 14, 2017 (Actual)

Study Completion Date

March 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novo Nordisk A/S

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes, Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1864 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Semaglutide 3 mg

Arm Type

Experimental

Arm Title

Semaglutide 7 mg

Arm Type

Experimental

Arm Title

Semaglutide 14 mg

Arm Type

Experimental

Arm Title

Sitagliptin 100 mg

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

semaglutide

Intervention Description

Oral administration once-daily

Intervention Type

Drug

Intervention Name(s)

sitagliptin

Intervention Description

Oral administration once-daily

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

Oral administration once-daily

Primary Outcome Measure Information:

Title

Change in HbA1c: Week 26

Description

Time Frame

Week 0, week 26

Secondary Outcome Measure Information:

Title

Change in Body Weight: Week 26

Description

Time Frame

Week 0, week 26

Title

Change in HbA1c: Weeks 52 and 78

Description

Time Frame

Week 0, week 52, week 78

Title

Change in Body Weight (kg): Weeks 52 and 78

Description

Time Frame

Week 0, week 52, week 78

Title

Change in Body Weight (%)

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in FPG

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in BMI

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in Waist Circumference

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in Total Cholesterol (Ratio to Baseline)

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in LDL Cholesterol (Ratio to Baseline)

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in VLDL Cholesterol (Ratio to Baseline)

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in HDL Cholesterol (Ratio to Baseline)

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in Triglycerides (Ratio to Baseline)

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in Free Fatty Acids (Ratio to Baseline)

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in SMPG - Mean 7-point Profile

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in SMPG - Mean Postprandial Increment Over All Meals

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)

Description

Time Frame

Week 26, week 52, week 78

Title

Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)

Description

Time Frame

Week 26, week 52, week 78

Title

Participants Who Achieve Weight Loss ≥5% (Yes/no)

Description

Time Frame

Week 26, week 52, week 78

Title

Participants Who Achieve Weight Loss ≥10% (Yes/no)

Description

Time Frame

Week 26, week 52, week 78

Title

Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)

Description

Time Frame

Week 26, week 52, week 78

Title

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Description

Time Frame

Week 26, week 52, week 78

Title

Time to Additional Anti-diabetic Medication

Description

Time Frame

Weeks 0-78

Title

Time to Rescue Medication

Description

Time Frame

Weeks 0-78

Title

Number of TEAEs During Exposure to Trial Product

Description

Time Frame

Weeks 0-83

Title

Change in Amylase (Ratio to Baseline)

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in Lipase (Ratio to Baseline)

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in Pulse Rate

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in SBP and DBP

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in ECG Evaluation

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in Physical Examination

Description

Time Frame

Week -2, week 52, week 78

Title

Change in Eye Examination Category

Description

Time Frame

Week -2, week 52, week 78

Title

Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)

Description

Time Frame

Weeks 0-83

Title

Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)

Description

Time Frame

Weeks 0-83

Title

Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no)

Description

This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time Frame

Weeks 0-83

Title

Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)

Description

This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide neutralising antibodies cross reacting with native GLP-1 anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Time Frame

Weeks 0-83

Title

Anti-semaglutide Binding Antibody Levels

Description

Time Frame

Weeks 0-83

Title

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Description

Time Frame

Weeks 0-83

Title

Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Description

Time Frame

Weeks 0-83

Title

Semaglutide Plasma Concentration in a Subset of the Participants for Population PK Analyses

Description

Time Frame

Weeks 0-83

Title

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains

Description

Time Frame

Week 0, week 26, week 52, week 78

Title

Change in CoEQ: Scores From the 4 Domains and the 19 Items

Description

Time Frame

Week 0, week 26, week 52, week 78

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female, age at least 18 years at the time of signing informed consent For Japan only: Male or female, age at least 20 years at the time of signing informed consent Diagnosed with T2DM (type 2 diabetes mellitus) for at least 90 days prior to day of screening HbA1c (glycosylated haemoglobin) 7.0-10.5 % (53-91 mmol/mol) (both inclusive). Stable daily dose of metformin (equal or above 1500 mg or maximum tolerated dose as documented in subject medical record) alone or in combination with SU (= half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record) within 90 days prior to the day of screening Exclusion Criteria: Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice). For certain specific countries: Additional specific requirements apply Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN 2) or Medullary Thyroid Carcinoma (MTC) History of pancreatitis (acute or chronic) History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery) Any of the following: myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischaemic attack within the past 180 days prior to the day of screening Subjects presently classified as being in New York Heart Association (NYHA) Class IV. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening. Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinomas)

Facility Information:

Facility Name

Novo Nordisk Investigational Site

City

Anniston

State/Province

Alabama

ZIP/Postal Code

36207

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35211

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Tuscumbia

State/Province

Alabama

ZIP/Postal Code

35674

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Glendale

State/Province

Arizona

ZIP/Postal Code

85308

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72212

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Carmichael

State/Province

California

ZIP/Postal Code

95608

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Coronado

State/Province

California

ZIP/Postal Code

92118

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Encino

State/Province

California

ZIP/Postal Code

91436

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Fresno

State/Province

California

ZIP/Postal Code

93720

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Los Alamitos

State/Province

California

ZIP/Postal Code

90720

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Palm Springs

State/Province

California

ZIP/Postal Code

92262

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Poway

State/Province

California

ZIP/Postal Code

92064

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Walnut Creek

State/Province

California

ZIP/Postal Code

94598

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Denver

State/Province

Colorado

ZIP/Postal Code

80220

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Kissimmee

State/Province

Florida

ZIP/Postal Code

34741

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

New Port Richey

State/Province

Florida

ZIP/Postal Code

34652

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Palm Harbor

State/Province

Florida

ZIP/Postal Code

34684

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Plantation

State/Province

Florida

ZIP/Postal Code

33324

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Port Charlotte

State/Province

Florida

ZIP/Postal Code

33952

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Spring Hill

State/Province

Florida

ZIP/Postal Code

34609

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Tampa

State/Province

Florida

ZIP/Postal Code

33607

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Marietta

State/Province

Georgia

ZIP/Postal Code

30060

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Perry

State/Province

Georgia

ZIP/Postal Code

31069

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Honolulu

State/Province

Hawaii

ZIP/Postal Code

96814

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Meridian

State/Province

Idaho

ZIP/Postal Code

83646

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Gurnee

State/Province

Illinois

ZIP/Postal Code

60031

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Peoria

State/Province

Illinois

ZIP/Postal Code

61602

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Peoria

State/Province

Illinois

ZIP/Postal Code

61603

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Avon

State/Province

Indiana

ZIP/Postal Code

46123

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Park City

State/Province

Kansas

ZIP/Postal Code

67219

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40503

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40213

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Paducah

State/Province

Kentucky

ZIP/Postal Code

42001

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Paducah

State/Province

Kentucky

ZIP/Postal Code

42003

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Metairie

State/Province

Louisiana

ZIP/Postal Code

70002

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Natchitoches

State/Province

Louisiana

ZIP/Postal Code

71457-5881

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Shreveport

State/Province

Louisiana

ZIP/Postal Code

71105

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Rockville

State/Province

Maryland

ZIP/Postal Code

20852

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Waltham

State/Province

Massachusetts

ZIP/Postal Code

02453

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Flint

State/Province

Michigan

ZIP/Postal Code

48532

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Sterling Heights

State/Province

Michigan

ZIP/Postal Code

48310-3503

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Jefferson City

State/Province

Missouri

ZIP/Postal Code

65109

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Butte

State/Province

Montana

ZIP/Postal Code

59701-1652

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Teaneck

State/Province

New Jersey

ZIP/Postal Code

07666

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Trenton

State/Province

New Jersey

ZIP/Postal Code

08611

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87102

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

New Windsor

State/Province

New York

ZIP/Postal Code

12553

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Rochester

State/Province

New York

ZIP/Postal Code

14607

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

West Seneca

State/Province

New York

ZIP/Postal Code

14224

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28277

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

High Point

State/Province

North Carolina

ZIP/Postal Code

27265

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Statesville

State/Province

North Carolina

ZIP/Postal Code

28625

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Whiteville

State/Province

North Carolina

ZIP/Postal Code

28472

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Wilmington

State/Province

North Carolina

ZIP/Postal Code

28401

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Fargo

State/Province

North Dakota

ZIP/Postal Code

58104

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45219

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45236

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43203

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43213

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Franklin

State/Province

Ohio

ZIP/Postal Code

45005

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Maumee

State/Province

Ohio

ZIP/Postal Code

43537

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Toledo

State/Province

Ohio

ZIP/Postal Code

43623

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Norman

State/Province

Oklahoma

ZIP/Postal Code

73069

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Corvallis

State/Province

Oregon

ZIP/Postal Code

97330-3737

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Jersey Shore

State/Province

Pennsylvania

ZIP/Postal Code

17740

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

McMurray

State/Province

Pennsylvania

ZIP/Postal Code

15317

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Gaffney

State/Province

South Carolina

ZIP/Postal Code

29341

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Greer

State/Province

South Carolina

ZIP/Postal Code

29651

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Pelzer

State/Province

South Carolina

ZIP/Postal Code

29669

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Summerville

State/Province

South Carolina

ZIP/Postal Code

29485

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Bristol

State/Province

Tennessee

ZIP/Postal Code

37620-7352

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Humboldt

State/Province

Tennessee

ZIP/Postal Code

38343

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Jackson

State/Province

Tennessee

ZIP/Postal Code

38305

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Amarillo

State/Province

Texas

ZIP/Postal Code

79106

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75226

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75230

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390-9302

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77074

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77081

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Longview

State/Province

Texas

ZIP/Postal Code

75605

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Plano

State/Province

Texas

ZIP/Postal Code

75093

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78209

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78224

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Sugar Land

State/Province

Texas

ZIP/Postal Code

77478

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Waco

State/Province

Texas

ZIP/Postal Code

76710

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Murray

State/Province

Utah

ZIP/Postal Code

84123

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

South Burlington

State/Province

Vermont

ZIP/Postal Code

05403

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23219

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Olympia

State/Province

Washington

ZIP/Postal Code

98502

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Renton

State/Province

Washington

ZIP/Postal Code

98057

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Spokane

State/Province

Washington

ZIP/Postal Code

99218

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Milwaukee

State/Province

Wisconsin

ZIP/Postal Code

53202

Country

United States

Facility Name

Novo Nordisk Investigational Site

City

Caba

ZIP/Postal Code

1425

Country

Argentina

Facility Name

Novo Nordisk Investigational Site

City

Caba

ZIP/Postal Code

C1060ABA

Country

Argentina

Facility Name

Novo Nordisk Investigational Site

City

Caba

ZIP/Postal Code

C1179AAB

Country

Argentina

Facility Name

Novo Nordisk Investigational Site

City

Capital Federal

ZIP/Postal Code

C1056ABJ

Country

Argentina

Facility Name

Novo Nordisk Investigational Site

City

Cordoba

ZIP/Postal Code

5000

Country

Argentina

Facility Name

Novo Nordisk Investigational Site

City

Córdoba

ZIP/Postal Code

5008

Country

Argentina

Facility Name

Novo Nordisk Investigational Site

City

São Paulo

State/Province

Sao Paulo

ZIP/Postal Code

01228-200

Country

Brazil

Facility Name

Novo Nordisk Investigational Site

City

Angers

ZIP/Postal Code

49000

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Chalons-en-Champagne Cedex

ZIP/Postal Code

51005

Country

France

Facility Name

Novo Nordisk Investigational Site

City

DIJON cedex

ZIP/Postal Code

21079

Country

France

Facility Name

Novo Nordisk Investigational Site

City

LA ROCHE-sur-YON cedex 9

ZIP/Postal Code

85295

Country

France

Facility Name

Novo Nordisk Investigational Site

City

LA ROCHELLE cedex

ZIP/Postal Code

17019

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Le Creusot

ZIP/Postal Code

71200

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Limoges

ZIP/Postal Code

87000

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Marseille

ZIP/Postal Code

13006

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Nanterre

ZIP/Postal Code

92014

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Nantes Cedex 01

ZIP/Postal Code

448093

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Nantes

ZIP/Postal Code

44200

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Narbonne

ZIP/Postal Code

11108

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Paris

ZIP/Postal Code

75877

Country

France

Facility Name

Novo Nordisk Investigational Site

City

PERPIGNAN cedex

ZIP/Postal Code

66046

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Périgueux

ZIP/Postal Code

24019

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Venissieux

ZIP/Postal Code

69200

Country

France

Facility Name

Novo Nordisk Investigational Site

City

Bad Mergentheim

ZIP/Postal Code

97980

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Berlin

ZIP/Postal Code

12163

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Elsterwerda

ZIP/Postal Code

04910

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Essen

ZIP/Postal Code

45219

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Falkensee

ZIP/Postal Code

14612

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Friedrichsthal

ZIP/Postal Code

66299

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Hamburg

ZIP/Postal Code

22607

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Münster

ZIP/Postal Code

48145

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Saint Ingbert-Oberwürzbach

ZIP/Postal Code

66386

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Stuttgart

ZIP/Postal Code

70378

Country

Germany

Facility Name

Novo Nordisk Investigational Site

City

Hyderabad

State/Province

Andhra Pradesh

ZIP/Postal Code

500034

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Hyderabad

State/Province

Andhra Pradesh

ZIP/Postal Code

500072

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Gurgaon

State/Province

Haryana

ZIP/Postal Code

122001

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Bangalore

State/Province

Karnataka

ZIP/Postal Code

560 017

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Mumbai

State/Province

Maharashtra

ZIP/Postal Code

4000016

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Mumbai

State/Province

Maharashtra

ZIP/Postal Code

400008

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Pune

State/Province

Maharashtra

ZIP/Postal Code

411040

Country

India

Facility Name

Novo Nordisk Investigational Site

City

New Dehli

State/Province

New Delhi

ZIP/Postal Code

110029

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Bhubaneshwar

State/Province

Orissa

ZIP/Postal Code

751003

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Chandigarh

State/Province

Punjab

ZIP/Postal Code

160012

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Jaipur

State/Province

Rajasthan

ZIP/Postal Code

302004

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Jaipur

State/Province

Rajasthan

ZIP/Postal Code

302006

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Chennai

State/Province

Tamil Nadu

ZIP/Postal Code

600 013

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Chennai

State/Province

Tamil Nadu

ZIP/Postal Code

600086

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Vellore

State/Province

Tamil Nadu

ZIP/Postal Code

632004

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Kolkata

State/Province

West Bengal

ZIP/Postal Code

700014

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Kolkata

State/Province

West Bengal

ZIP/Postal Code

700020

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Kolkata

State/Province

West Bengal

ZIP/Postal Code

700064

Country

India

Facility Name

Novo Nordisk Investigational Site

City

Haifa

ZIP/Postal Code

31096

Country

Israel

Facility Name

Novo Nordisk Investigational Site

City

Holon

ZIP/Postal Code

58100

Country

Israel

Facility Name

Novo Nordisk Investigational Site

City

Jerusalem

ZIP/Postal Code

91120

Country

Israel

Facility Name

Novo Nordisk Investigational Site

City

Kfar Saba

ZIP/Postal Code

44281

Country

Israel

Facility Name

Novo Nordisk Investigational Site

City

Petah-Tikva

ZIP/Postal Code

49100

Country

Israel

Facility Name

Novo Nordisk Investigational Site

City

Ra'anana

ZIP/Postal Code

43452

Country

Israel

Facility Name

Novo Nordisk Investigational Site

City

Tel Aviv

ZIP/Postal Code

6937947

Country

Israel

Facility Name

Novo Nordisk Investigational Site

City

Tel-Aviv

ZIP/Postal Code

64239

Country

Israel

Facility Name

Novo Nordisk Investigational Site

City

Asahikawa-shi, Hokkaido

ZIP/Postal Code

070-0002

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Gunma

ZIP/Postal Code

373-0036

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Hokkaido

ZIP/Postal Code

060-0062

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Ibaraki

ZIP/Postal Code

311-0113

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Iruma-shi, Saitama

ZIP/Postal Code

358-0011

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Kanagawa

ZIP/Postal Code

235-0045

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Kashiwara-shi, Osaka

ZIP/Postal Code

582-0005

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Kyoto-shi, Kyoto

ZIP/Postal Code

601-1495

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Kyoto-shi, Kyoto

ZIP/Postal Code

615-0035

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Miyazaki

ZIP/Postal Code

880-0034

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Osaka

ZIP/Postal Code

569-1045

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Shinjuku-ku, Tokyo

ZIP/Postal Code

162-8655

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Shizuoka-shi, Shizuoka

ZIP/Postal Code

424-0853

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Tokyo

ZIP/Postal Code

103-0027

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Tokyo

ZIP/Postal Code

103-0028

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Tokyo

ZIP/Postal Code

113-8431

Country

Japan

Facility Name

Novo Nordisk Investigational Site

City

Toluca

State/Province

Estado De México

ZIP/Postal Code

50130

Country

Mexico

Facility Name

Novo Nordisk Investigational Site

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44670

Country

Mexico

Facility Name

Novo Nordisk Investigational Site

City

Ciudad Madero

State/Province

Tamaulipas

ZIP/Postal Code

89440

Country

Mexico

Facility Name

Novo Nordisk Investigational Site

City

Aguascalientes

ZIP/Postal Code

20230

Country

Mexico

Facility Name

Novo Nordisk Investigational Site

City

San Luis Potosi

ZIP/Postal Code

78200

Country

Mexico

Facility Name

Novo Nordisk Investigational Site

City

Pitesti

State/Province

Arges

ZIP/Postal Code

110084

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Oradea

State/Province

Bihor

ZIP/Postal Code

410025

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Craiova

State/Province

Dolj

ZIP/Postal Code

200642

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Baia Mare

State/Province

Maramures

ZIP/Postal Code

430222

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Targu Mures

State/Province

Mures

ZIP/Postal Code

540098

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Ploiesti

State/Province

Prahova

ZIP/Postal Code

100342

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Timisoara

State/Province

Timis

ZIP/Postal Code

300125

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Bucharest

ZIP/Postal Code

020359

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Bucharest

ZIP/Postal Code

020475

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Iasi

ZIP/Postal Code

700111

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Iasi

ZIP/Postal Code

700469

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Satu Mare

ZIP/Postal Code

440055

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Timisoara

ZIP/Postal Code

300736

Country

Romania

Facility Name

Novo Nordisk Investigational Site

City

Barnaul

ZIP/Postal Code

656045

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Moscow

ZIP/Postal Code

117036

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Moscow

ZIP/Postal Code

117292

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Moscow

ZIP/Postal Code

119435

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Novosibirsk

ZIP/Postal Code

630047

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Penza

ZIP/Postal Code

440026

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Tomsk

ZIP/Postal Code

634041

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Tomsk

ZIP/Postal Code

634050

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Yaroslavl

ZIP/Postal Code

150062

Country

Russian Federation

Facility Name

Novo Nordisk Investigational Site

City

Port Elizabeth

State/Province

Eastern Cape

ZIP/Postal Code

6045

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Bloemfontein

State/Province

Free State

ZIP/Postal Code

9301

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Johannesburg

State/Province

Gauteng

ZIP/Postal Code

1818

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Johannesburg

State/Province

Gauteng

ZIP/Postal Code

1829

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Johannesburg

State/Province

Gauteng

ZIP/Postal Code

2001

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Johannesburg

State/Province

Gauteng

ZIP/Postal Code

2198

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Krugersdorp

State/Province

Gauteng

ZIP/Postal Code

1739

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Pretoria

State/Province

Gauteng

ZIP/Postal Code

0122

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Durban

State/Province

KwaZulu-Natal

ZIP/Postal Code

4120

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Cape Town

State/Province

Western Cape

ZIP/Postal Code

7130

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Cape Town

ZIP/Postal Code

7530

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Pretoria

ZIP/Postal Code

0101

Country

South Africa

Facility Name

Novo Nordisk Investigational Site

City

Ankara

ZIP/Postal Code

06100

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Istanbul

ZIP/Postal Code

34147

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Istanbul

ZIP/Postal Code

34371

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Istanbul

ZIP/Postal Code

34718

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Istanbul

ZIP/Postal Code

34722

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

İstanbul

ZIP/Postal Code

34752

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Istanbul

ZIP/Postal Code

34890

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Istanbul

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Izmir

ZIP/Postal Code

35340

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Samsun

ZIP/Postal Code

55139

Country

Turkey

Facility Name

Novo Nordisk Investigational Site

City

Cherkasy

ZIP/Postal Code

18009

Country

Ukraine

Facility Name

Novo Nordisk Investigational Site

City

Ivano-Frankivsk

ZIP/Postal Code

76018

Country

Ukraine

Facility Name

Novo Nordisk Investigational Site

City

Kyiv

ZIP/Postal Code

04114

Country

Ukraine

Facility Name

Novo Nordisk Investigational Site

City

Mykolaiv

ZIP/Postal Code

54003

Country

Ukraine

Facility Name

Novo Nordisk Investigational Site

City

Odesa

ZIP/Postal Code

65025

Country

Ukraine

Facility Name

Novo Nordisk Investigational Site

City

Ternopil

ZIP/Postal Code

46002

Country

Ukraine

Facility Name

Novo Nordisk Investigational Site

City

Zaporizhia

ZIP/Postal Code

69600

Country

Ukraine

Facility Name

Novo Nordisk Investigational Site

City

Zhytomyr

ZIP/Postal Code

10002

Country

Ukraine

Facility Name

Novo Nordisk Investigational Site

City

Basingstoke

ZIP/Postal Code

RG24 9GT

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Cardiff

ZIP/Postal Code

CF5 4AD

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Chester

ZIP/Postal Code

CH2 1UL

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Crewe

ZIP/Postal Code

CW5 5NX

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Doncaster

ZIP/Postal Code

DN9 2HY

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Leicester

ZIP/Postal Code

LE5 4PW

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Plymouth

ZIP/Postal Code

PL6 8DH

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Preston

ZIP/Postal Code

PR2 9HT

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Rotherham

ZIP/Postal Code

S651DA

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Sidcup

ZIP/Postal Code

DA14 6LT

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Soham

ZIP/Postal Code

CB7 5JD

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Swansea

ZIP/Postal Code

SA2 8PP

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Taunton

ZIP/Postal Code

TA1 5DA

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Torquay

ZIP/Postal Code

TQ2 7AA

Country

United Kingdom

Facility Name

Novo Nordisk Investigational Site

City

Wellingborough

ZIP/Postal Code

NN8 4RW

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Citations:

PubMed Identifier

30903796

Citation

Rosenstock J, Allison D, Birkenfeld AL, Blicher TM, Deenadayalan S, Jacobsen JB, Serusclat P, Violante R, Watada H, Davies M; PIONEER 3 Investigators. Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial. JAMA. 2019 Apr 16;321(15):1466-1480. doi: 10.1001/jama.2019.2942.

Results Reference

result

PubMed Identifier

34472698

Citation

Araki E, Terauchi Y, Watada H, Deenadayalan S, Christiansen E, Horio H, Kadowaki T. Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 trials. Diabetes Obes Metab. 2021 Dec;23(12):2785-2794. doi: 10.1111/dom.14536. Epub 2021 Sep 27.

Results Reference

result

PubMed Identifier

35064550

Citation

Eliasson B, Ericsson A, Fridhammar A, Nilsson A, Persson S, Chubb B. Long-Term Cost Effectiveness of Oral Semaglutide Versus Empagliflozin and Sitagliptin for the Treatment of Type 2 Diabetes in the Swedish Setting. Pharmacoecon Open. 2022 May;6(3):343-354. doi: 10.1007/s41669-021-00317-z. Epub 2022 Jan 21.

Results Reference

result

PubMed Identifier

35373893

Citation

Aroda VR, Bauer R, Christiansen E, Haluzik 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. doi: 10.1111/dom.14710. Epub 2022 May 9.

Results Reference

result

PubMed Identifier

33660198

Citation

Pratley RE, Crowley MJ, Gislum M, Hertz CL, Jensen TB, Khunti K, Mosenzon O, Buse JB. Oral Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses. Diabetes Ther. 2021 Apr;12(4):1099-1116. doi: 10.1007/s13300-020-00994-9. Epub 2021 Mar 4.

Results Reference

derived

PubMed Identifier

32998732

Citation

Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4.

Results Reference

derived

PubMed Identifier

32267058

Citation

Thethi TK, Pratley R, Meier JJ. Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme. Diabetes Obes Metab. 2020 Aug;22(8):1263-1277. doi: 10.1111/dom.14054. Epub 2020 May 13.

Results Reference

derived

PubMed Identifier

31903692

Citation

Husain M, Bain SC, Jeppesen OK, Lingvay I, Sorrig R, Treppendahl MB, Vilsboll T. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5.

Results Reference

derived

Links:

URL

http://novonordisk-trials.com

Description

Clinical Trials at Novo Nordisk

Learn more about this trial

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

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Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes (PIONEER 3)

Diabetes, Diabetes Mellitus, Type 2

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial