Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

Short name PIONEER PLUS

NCTNCT04707469Other idNN9924-4635Other idU1111-1247-0210Other id2020-000299-39

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 3
Enrollment: 1,606 participants (actual)
Sponsor: Novo Nordisk A/S · Industry
Design: Randomized · Quadruple masking
Countries: 15 countries
United States, Australia, Bulgaria, Canada, Croatia, Czechia, Estonia, Germany, Hungary, India, Poland, Puerto Rico, Slovakia, Slovenia, Taiwan
Start: 15 Jan 2021
Primary completion: 7 Mar 2023
Completion: 8 Mar 2023
First posted: 13 Jan 2021
Last update posted: 9 Dec 2025
Conditions: Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2021202220232024

Ph 3
PIONEER PLUS
NCT04707469
15 Jan 2021 to 8 Mar 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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®.

Interventions

Oral semaglutideDrug

Arms3

Experimental
Oral semaglutide 50 mg
Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12), 25 mg (week 13-16) and 50 mg (week 17-68).
Experimental
Oral semaglutide 25 mg
Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12) and 25 mg (week 13-68).
Active comparator
Oral semaglutide 14 mg
Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8) and 14 mg (week 9-68).

Primary outcomes1

Outcomes the sponsor listed as primary.

Change From Baseline in Glycated Haemoglobin (HbA1c) (Week 52)
Time frame · Baseline (week 0), week 52
Registry description
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(20)

Change From Baseline in Body Weight (Week 52)
Time frame · Baseline (week 0), week 52
Registry description
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.
Change From Baseline in HbA1c (Week 68)
Time frame · Baseline (week 0), week 68
Registry description
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.
Change From Week 12 in HbA1c (Week 52)
Time frame · Week 12, Week 52
Registry description
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.
Change From Baseline in Fasting Plasma Glucose (FPG) (Week 52)
Time frame · Baseline (week 0), week 52
Registry description
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.
Change From Baseline in FPG (Week 68)
Time frame · Baseline (week 0), week 68
Registry description
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.
Percentage of Participants Who Achieved HbA1c Less Than (<) 7.0 (Percent [%]) (Week 52)
Time frame · At week 52
Registry description
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.
Percentage of Participants Who Achieved HbA1c < 7.0 % (Week 68)
Time frame · At week 68
Registry description
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.
Percentage of Participants Who Achieved HbA1c Less Than or Equal to (<=) 6.5 % (Week 52)
Time frame · At week 52
Registry description
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.
Percentage of Participants Who Achieved HbA1c <= 6.5 % (Week 68)
Time frame · At week 68
Registry description
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.
Time to Event Analyses of Rescue Medication
Time frame · Baseline (week 0), week 68
Registry description
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.
Change From Baseline in Body Weight (Week 68)
Time frame · Baseline (week 0), week 68
Registry description
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.
Percentage Change From Baseline in Body Weight (Week 52)
Time frame · Baseline (week 0), week 52
Registry description
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.
Percentage Change From Baseline in Body Weight (Week 68)
Time frame · Baseline (week 0), week 68
Registry description
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.
Percentage Change From Week 12 in Body Weight (Week 52)
Time frame · Week 12, Week 52
Registry description
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.
Change From Baseline in Body Mass Index (BMI) (Week 52)
Time frame · Baseline (week 0), week 52
Registry description
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.
Change From Baseline in BMI (Week 68)
Time frame · Baseline (week 0), week 68
Registry description
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.
Change From Baseline in Waist Circumference (Week 52)
Time frame · Baseline (week 0), week 52
Registry description
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.
Change From Baseline in Waist Circumference (Week 68)
Time frame · Baseline (week 0), week 68
Registry description
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.
Percentage of Participants Who Achieved Weight Loss Greater Than or Equal to (>=) 5 % (Week 52)
Time frame · At week 52
Registry description
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.
Percentage of Participants Who Achieved Weight Loss >= 5 % (Week 68)
Time frame · At week 68
Registry description
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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Baseline (week 0), week 52

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

Group	Value (Percentage point of HbA1c)	Spread
Oral Semaglutide 14 mg	-1.5	1.3
Oral Semaglutide 25 mg	-1.9	1.3
Oral Semaglutide 50 mg	-2.1	1.4

Secondary and other outcome results(7)

Secondary outcomeMean· Baseline (week 0), week 52

Change From Baseline in Body Weight (Week 52)

Group	Value (Kilogram (Kg))	Spread
Oral Semaglutide 14 mg	-4.4	5.2
Oral Semaglutide 25 mg	-7.1	6.8
Oral Semaglutide 50 mg	-8.3	7.5

Secondary outcomeMean· Baseline (week 0), week 68

Change From Baseline in HbA1c (Week 68)

Group	Value (Percentage point of HbA1c)	Spread
Oral Semaglutide 14 mg	-1.5	1.3
Oral Semaglutide 25 mg	-1.8	1.3
Oral Semaglutide 50 mg	-2.0	1.4

Secondary outcomeMean· Week 12, Week 52

Change From Week 12 in HbA1c (Week 52)

Group	Value (Percentage point of HbA1c)	Spread
Oral Semaglutide 14 mg	-0.4	1.2
Oral Semaglutide 25 mg	-0.8	1.1
Oral Semaglutide 50 mg	-1.0	1.2

Secondary outcomeMean· Baseline (week 0), week 52

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

Group	Value (millimole per litre (mmol/L))	Spread
Oral Semaglutide 14 mg	-2.4	3.4
Oral Semaglutide 25 mg	-3.0	3.5
Oral Semaglutide 50 mg	-3.2	3.4

Secondary outcomeMean· Baseline (week 0), week 68

Change From Baseline in FPG (Week 68)

Group	Value (mmol/L)	Spread
Oral Semaglutide 14 mg	-2.4	3.4
Oral Semaglutide 25 mg	-3.0	3.7
Oral Semaglutide 50 mg	-3.2	3.4

Secondary outcomeNumber· At week 52

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

Group	Value (Percentage of Participants)
Oral Semaglutide 14 mg	39
Oral Semaglutide 25 mg	50.5
Oral Semaglutide 50 mg	63

Secondary outcomeNumber· At week 68

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

Group	Value (Percentage of Participants)
Oral Semaglutide 14 mg	39.2
Oral Semaglutide 25 mg	49.9
Oral Semaglutide 50 mg	58.9

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Oral Semaglutide 14 mgParticipants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 68: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 68.	2 / 534	53 / 534	277 / 534
Oral Semaglutide 25 mgParticipants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 68: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to 12 and 25 mg from week 12 to week 68.	6 / 534	57 / 534	294 / 534
Oral Semaglutide 50 mgParticipants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 68: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to 12, 25 mg from week 12 to week 16 and 50 mg from week 16 to week 68.	2 / 534	44 / 534	314 / 534

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2023

8 results

Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial.

Aroda et al. 2023Lancet (London, England)cited by 83

PMID 37385279DOI 10.1016/s0140-6736(23)01127-3PUB-37385279

Rights unknown8 results

Source link See results (8)

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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.

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