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Completed

NCT Number: NCT04707469

Research Study to Compare Three Doses of Semaglutide Tablets Taken Once Daily in People With Type 2 Diabetes

This study compares three doses of once daily semaglutide tablets in people with type 2 diabetes who were previously treated with other oral anti-diabetic medicines. Participants will be initiated on the lowest starting dose of 3 mg and gradually increased until they reach the final trial dose of 14 mg, 25 mg or 50 mg once daily semaglutide tablets. The final three doses will be randomized (i.e., decided by chance). Participants will be administered one tablet per day for 68 weeks. Women cannot take part if they are pregnant, breast-feeding or planning to become pregnant during the study period. Women who can get pregnant will be checked for pregnancy via urine tests. Once daily semaglutide tablets (3 mg, 7 mg and 14 mg) are approved for the treatment of type 2 diabetes in the US, in the EU and in some other countries, under the brand name Rybelsus®.

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Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Liverpool Hospital, Liverpool, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female, age above or equal to 18 years at the time of signing informed consent.
  • Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening.
  • HbA1c of 8.0-10.5% (64-91 mmol/mol) (both inclusive).
  • BMI equal to or above 25 kg/m^2
  • Stable daily dose(s) for 90 days prior to the day of screening of any of the following treatment regimens:
  • No more than 3 of the following oral anti-diabetic drugs and at least 1 marked with a *:
  • Metformin (equal to or above1500 mg or maximum tolerated or effective dose).
  • Sulfonylureas (SU) (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose).
  • Sodium/glucose cotransporter 2 (SGLT2) inhibitors (maximum tolerated dose).
  • Dipeptidyl peptidase-4 (DPP-4) inhibitors (maximally indicated dose as per local label).
  • Subjects, on treatment with stable dose of DPP-4 inhibitors at inclusion, must be willing to discontinue DPP-4 inhibitor treatment at randomisation (with no wash-out).

Exclusion criteria

  • Treatment with any medication indicated for the treatment of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed.
  • Renal impairment measured as estimated glomerular filtration rate (eGFR) value of below 30 mL/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO 2012) classification.
  • Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Treatment and study plan

Oral semaglutide

Drug

Participants will receive once daily semaglutide tablets (oral administration) in a dose escalating manner for 68 weeks.

Primary outcomes

  1. Change From Baseline in Glycated Haemoglobin (HbA1c) (Week 52)

    Time frame: Baseline (week 0), week 52

    Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment. Percentage point refers to arithmetic difference between two percentages.

Secondary outcomes

  1. Change From Baseline in Body Weight (Week 52)

    Time frame: Baseline (week 0), week 52

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

  2. Change From Baseline in HbA1c (Week 68)

    Time frame: Baseline (week 0), week 68

    Change from baseline (week 0) in HbA1c was evaluated at week 68. 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 additional anti-diabetic medication or discontinuation of trial treatment. Percentage point refers to arithmetic difference between two percentages.

  3. Change From Week 12 in HbA1c (Week 52)

    Time frame: Week 12, Week 52

    Change in HbA1c was evaluated from week 12 to week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment. Percentage point refers to arithmetic difference between two percentages.

  4. Change From Baseline in Fasting Plasma Glucose (FPG) (Week 52)

    Time frame: Baseline (week 0), week 52

    Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

  5. Change From Baseline in FPG (Week 68)

    Time frame: Baseline (week 0), week 68

    Change from baseline (week 0) in FPG was evaluated at week 68. 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 additional anti-diabetic medication or discontinuation of trial treatment.

  6. Percentage of Participants Who Achieved HbA1c Less Than (<) 7.0 (Percent [%]) (Week 52)

    Time frame: At week 52

    Percentage of participants who achieved HbA1c <7.0 % at week 52 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 additional anti-diabetic medication or discontinuation of trial treatment.

  7. Percentage of Participants Who Achieved HbA1c < 7.0 % (Week 68)

    Time frame: At week 68

    Percentage of participants who achieved HbA1c <7.0 % at week 68 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 additional anti-diabetic medication or discontinuation of trial treatment.

  8. Percentage of Participants Who Achieved HbA1c Less Than or Equal to (<=) 6.5 % (Week 52)

    Time frame: At week 52

    Percentage of participants who achieved HbA1c <=6.5 % at week 52 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 additional anti-diabetic medication or discontinuation of trial treatment.

  9. Percentage of Participants Who Achieved HbA1c <= 6.5 % (Week 68)

    Time frame: At week 68

    Percentage of participants who achieved HbA1c <=6.5 % at week 68 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 additional anti-diabetic medication or discontinuation of trial treatment.

  10. Time to Event Analyses of Rescue Medication

    Time frame: Baseline (week 0), week 68

    Time to event analyses of rescue medication was evaluated from baseline (week 0) to week 68. 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 additional anti-diabetic medication or discontinuation of trial treatment.

  11. Change From Baseline in Body Weight (Week 68)

    Time frame: Baseline (week 0), week 68

    Change from baseline (week 0) in body weight was evaluated at week 68. 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 additional anti-diabetic medication or discontinuation of trial treatment.

  12. Percentage Change From Baseline in Body Weight (Week 52)

    Time frame: Baseline (week 0), week 52

    Percentage change from baseline (week 0) in body weight was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

  13. Percentage Change From Baseline in Body Weight (Week 68)

    Time frame: Baseline (week 0), week 68

    Percentage change from baseline (week 0) in body weight was evaluated at week 68. 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 additional anti-diabetic medication or discontinuation of trial treatment.

  14. Percentage Change From Week 12 in Body Weight (Week 52)

    Time frame: Week 12, Week 52

    Percentage change in body weight was evaluated from week 12 to week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

  15. Change From Baseline in Body Mass Index (BMI) (Week 52)

    Time frame: Baseline (week 0), week 52

    Change from baseline (week 0) in body mass index (BMI) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

  16. Change From Baseline in BMI (Week 68)

    Time frame: Baseline (week 0), week 68

    Change from baseline (week 0) in BMI was evaluated at week 68. 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 additional anti-diabetic medication or discontinuation of trial treatment.

  17. Change From Baseline in Waist Circumference (Week 52)

    Time frame: Baseline (week 0), week 52

    Change from baseline (week 0) in waist circumference was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

  18. Change From Baseline in Waist Circumference (Week 68)

    Time frame: Baseline (week 0), week 68

    Change from baseline (week 0) in waist circumference was evaluated at week 68. 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 additional anti-diabetic medication or discontinuation of trial treatment.

  19. Percentage of Participants Who Achieved Weight Loss Greater Than or Equal to (>=) 5 % (Week 52)

    Time frame: At week 52

    Percentage of participants who achieved weight loss >= 5 % at week 52 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 additional anti-diabetic medication or discontinuation of trial treatment.

  20. Percentage of Participants Who Achieved Weight Loss >= 5 % (Week 68)

    Time frame: At week 68

    Percentage of participants who achieved weight loss >= 5 % at week 68 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 additional anti-diabetic medication or discontinuation of trial treatment.

  21. Percentage of Participants Who Achieved Weight Loss >= 10 % (Week 52)

    Time frame: At week 52

    Percentage of participants who achieved weight loss >= 10 % at week 52 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 additional anti-diabetic medication or discontinuation of trial treatment.

  22. Percentage of Participants Who Achieved Weight Loss >= 10 % (Week 68)

    Time frame: At week 68

    Percentage of participants who achieved weight loss >= 10 % at week 68 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 additional anti-diabetic medication or discontinuation of trial treatment.

  23. Change From Baseline in Total Cholesterol (Week 52)

    Time frame: Baseline, Week 52

    Change from baseline (week 0) in total cholesterol was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

  24. Change From Baseline in Total Cholesterol (Week 68)

    Time frame: Baseline, Week 68

    Change from baseline (week 0) in total cholesterol was evaluated at week 68. 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 additional anti-diabetic medication or discontinuation of trial treatment.

  25. Change From Baseline in Low Density Lipoproteins (LDL) (Week 52)

    Time frame: Baseline, Week 52

    Change from baseline (week 0) in LDL was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

  26. Change From Baseline in LDL (Week 68)

    Time frame: Baseline, Week 68

    Change from baseline (week 0) in LDL was evaluated at week 68. 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 additional anti-diabetic medication or discontinuation of trial treatment.

  27. Change From Baseline in High Density Lipoproteins (HDL) (Week 52)

    Time frame: Baseline, Week 52

    Change from baseline (week 0) in HDL was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

  28. Change From Baseline in HDL (Week 68)

    Time frame: Baseline, Week 68

    Change from baseline (week 0) in HDL was evaluated at week 68. 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 additional anti-diabetic medication or discontinuation of trial treatment.

  29. Change From Baseline in Triglycerides (Week 52)

    Time frame: Baseline, Week 52

    Change from baseline (week 0) in triglycerides was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of additional anti-diabetic medication or discontinuation of trial treatment.

  30. Change From Baseline in Triglycerides (Week 68)

    Time frame: Baseline, Week 68

    Change from baseline (week 0) in triglycerides was evaluated at week 68. 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 additional anti-diabetic medication or discontinuation of trial treatment.

  31. Number of Adverse Events

    Time frame: From baseline (week 0) up to week 73

    An adverse event (AE) defined as any unfavourable and unintended sign, including an abnormal laboratory finding, symptom or disease (new or exacerbated) temporally associated with the use of an investigational medicinal products (IMP). Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

  32. Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 Milligram Per Decilitre [mg/dL]) or Severe Hypoglycaemic Episodes (Level 3)

    Time frame: From baseline (week 0) up to week 68

    Hypoglycaemic episodes were classified according to the American Diabetes Association 2018/ International Hypoglycaemia Study Group 2017, where glycemic criteria for level 2 was < 3.0 mmol/L (54 mg/dL) and level 3 had no specific glucose threshold. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

  33. Change From Baseline in Systolic Blood Pressure (Week 52)

    Time frame: Baseline (week 0), week 52

    Change from baseline (week 0) in systolic blood pressure at week 52 are presented. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

  34. Change From Baseline in Systolic Blood Pressure (Week 68)

    Time frame: Baseline (week 0), week 68

    Change from baseline (week 0) in systolic blood pressure at week 68 are presented. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

  35. Change From Baseline in Diastolic Blood Pressure (Week 52)

    Time frame: Baseline (week 0), week 52

    Change from baseline (week 0) in diastolic blood pressure at week 52 are presented. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

  36. Change From Baseline in Diastolic Blood Pressure (Week 68)

    Time frame: Baseline (week 0), week 68

    Change from baseline (week 0) in diastolic blood pressure at week 68 are presented. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

  37. Change From Baseline in Pulse (Week 52)

    Time frame: Baseline (week 0), week 52

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

  38. Change From Baseline in Pulse (Week 68)

    Time frame: Baseline (week 0), week 68

    Change from baseline (week 0) in pulse at week 68 are presented. Results are based on the data from the on-treatment observation period, which was the time period when a participant was on trial treatment, including any period after initiation of rescue medication.

Sponsors and collaborators

Lead sponsor

Novo Nordisk A/S

Industry

Registry information

Official study title

Efficacy and Safety of Once-daily Oral Semaglutide 25 mg and 50 mg Compared With 14 mg in Subjects With Type 2 Diabetes

Acronym: PIONEER PLUS

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Jan 13, 2021
Registry last updated
Dec 9, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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