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Trial · Interventional

CompletedPhase 3Results postedRegistry data

Efficacy and Safety of Oral Semaglutide Versus Empagliflozin in Subjects With Type 2 Diabetes Mellitus

Short name PIONEER 2

NCTNCT02863328 (opens ClinicalTrials.gov in a new tab)Other idNN9924-4223Other id2015-005209-36Other idU1111-1176-6006Other id2015
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
822 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Open label (no masking)
Countries
12 countries

United States, Argentina, Brazil, Croatia, Greece, Hungary, Italy, Poland, Russia, Serbia, Spain, Thailand

Start
10 Aug 2016
Primary completion
1 Aug 2017
Completion
8 Mar 2018
First posted
11 Aug 2016 (estimated)
Last update posted
20 Jul 2022
Conditions
Diabetes · Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2016201720182019
  1. Ph 3

    PIONEER 2

    NCT02863328

    10 Aug 2016 to 8 Mar 2018

Registry summary

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

This trial is conducted globally. The aim of this trial is to investigate Efficacy and Safety of Oral Semaglutide versus Empagliflozin in Subjects with Type 2 Diabetes Mellitus.

Interventions

  • semaglutideDrug
  • empagliflozinDrug

Arms2

  • Experimental

    14 mg oral semaglutide

  • Active comparator

    25 mg empagliflozin

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change in HbA1c

    Time frame · Week 0, week 26

    Registry description

    Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on 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 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.

Secondary outcomes(20)

  1. Change in Body Weight (Kg)

    Time frame · Week 0, week 26

    Registry description

    Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on 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 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.

  2. Change in HbA1c (%)

    Time frame · Week 0, week 52

    Registry description

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

  3. Change in Body Weight (kg)

    Time frame · Week 0, week 52

    Registry description

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

  4. Change in Fasting Plasma Glucose

    Time frame · Week 0, week 26, week 52

    Registry description

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

  5. Change in SMPG : Mean of the 7-point Profile

    Time frame · Week 0, week 26 and week 52

    Registry description

    Change from baseline (week 0) in mean of the 7-point self-measured plasma glucose (SMPG) (i.e. before and after breakfast, lunch and dinner, and at bedtime) profile was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

  6. Change in SMPG : Mean Postprandial Increment Over All Meals

    Time frame · Week 0, week 26 and week 52

    Registry description

    Change from baseline (week 0) in mean postprandial glucose increment was evaluated at week 26 and week 52. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

  7. Change in Fasting C-peptide (Ratio to Baseline)

    Time frame · Week 0, week 26 and week 52

    Registry description

    Change from baseline (week 0) in fasting C-peptide (Nanomoles per liter \[nmol/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

  8. Change in Fasting Insulin (Ratio to Baseline)

    Time frame · Week 0, week 26 and week 52

    Registry description

    Change from baseline (week 0) in fasting insulin (picomoles per liter \[pmol/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

  9. Change in Fasting Pro-insulin (Ratio to Baseline)

    Time frame · Week 0, week 26 and week 52

    Registry description

    Change from baseline (week 0) in fasting pro-insulin (pmol/L) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

  10. Change in Fasting Glucagon (Ratio to Baseline)

    Time frame · Week 0, week 26 and week 52

    Registry description

    Change from baseline (week 0) in fasting glucagon (picograms per milliliter \[pg/mL\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

  11. Change in HOMA-IR (Ratio to Baseline)

    Time frame · Week 0, week 26 and week 52

    Registry description

    Change from baseline (week 0) in homeostatic model assessment index of insulin resistance (HOMA-IR) (%) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

  12. Change in HOMA-B (Ratio to Baseline)

    Time frame · Week 0, week 26 and week 52

    Registry description

    Change from baseline (week 0) in homeostatic model assessment index of beta-cell function (HOMA-B) (%) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

  13. Change in C-reactive Protein (Ratio to Baseline)

    Time frame · Week 0, week 26 and week 52

    Registry description

    Change from baseline (week 0) in C-reactive protein (milligrams per liter \[mg/L\]) at week 26 and week 52 is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.

  14. Change in Body Weight (%)

    Time frame · Week 0, week 26, week 52

    Registry description

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

  15. Change in Body Mass Index

    Time frame · Week 0, week 26, week 52

    Registry description

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

  16. Change in Waist Circumference

    Time frame · Week 0, week 26, week 52

    Registry description

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

  17. Change in Fasting Total Cholesterol (Ratio to Baseline)

    Time frame · Week 0, week 26 and week 52

    Registry description

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

  18. Change in Fasting LDL Cholesterol (Ratio to Baseline)

    Time frame · Week 0, week 26 and week 52

    Registry description

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

  19. Change in Fasting HDL Cholesterol (Ratio to Baseline)

    Time frame · Week 0, week 26 and week 52

    Registry description

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

  20. Change in Fasting VLDL Cholesterol (Ratio to Baseline)

    Time frame · Week 0, week 26 and week 52

    Registry description

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

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· Week 0, week 26

Change in HbA1c

GroupValue (Percentage-point of HbA1c)Spread
Oral Semaglutide 14 mg-1.31.1
Empagliflozin 25 mg-0.90.9
Secondary and other outcome results(7)
Secondary outcomeMean· Week 0, week 26

Change in Body Weight (Kg)

GroupValue (Kilogram (Kg))Spread
Oral Semaglutide 14 mg-3.94.4
Empagliflozin 25 mg-3.83.8
Secondary outcomeMean· Week 0, week 52

Change in HbA1c (%)

GroupValue (Percentage of HbA1c)Spread
Oral Semaglutide 14 mg-1.31.2
Empagliflozin 25 mg-0.91.0
Secondary outcomeMean· Week 0, week 52

Change in Body Weight (kg)

GroupValue (Kg)Spread
Oral Semaglutide 14 mg-4.05.5
Empagliflozin 25 mg-3.74.3
Secondary outcomeMean· Week 0, week 26, week 52

Change in Fasting Plasma Glucose

GroupValue (Millimoles per liter (mmol/L))Spread
Oral Semaglutide 14 mg-2.012.56
Empagliflozin 25 mg-2.082.17
Secondary outcomeMean· Week 0, week 26 and week 52

Change in SMPG : Mean of the 7-point Profile

GroupValue (mmol/L)Spread
Oral Semaglutide 14 mg-2.32.1
Empagliflozin 25 mg-1.92.1
Secondary outcomeMean· Week 0, week 26 and week 52

Change in SMPG : Mean Postprandial Increment Over All Meals

GroupValue (mmol/L)Spread
Oral Semaglutide 14 mg-0.51.8
Empagliflozin 25 mg-0.42.0
Secondary outcomeGeometric mean· Week 0, week 26 and week 52

Change in Fasting C-peptide (Ratio to Baseline)

GroupValue (Ratio of C-peptide)Spread
Oral Semaglutide 14 mg1.1035.7
Empagliflozin 25 mg0.8929.4

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Oral Semaglutide 14 mgParticipants received once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).0 / 41027 / 410128 / 410
Empagliflozin 25 mgParticipants received once-daily empagliflozin tablets for 52 weeks. Participants started empagliflozin at 10 mg for 8 weeks. Participants were treated with empagliflozin 25 mg if their eGFR was greater than or equal to 60 mL/min/1.73m\^2 from week 8 to week 52.1 / 40937 / 40944 / 409

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

Studies8

Studies that cite this trial.

Studies with results

2 studies on this page

Indexing hint: Meta-analysis (pooled) · 2020

4 results

Efficacy of Once-Weekly Semaglutide vs Empagliflozin Added to Metformin in Type 2 Diabetes: Patient-Level Meta-analysis.

Lingvay et al. 2020The Journal of clinical endocrinology and metabolismcited by 19

PMID 32827435PMC7549924DOI 10.1210/clinem/dgaa577PUB-32827435

CC BY4 results
Download PDFSee results (4)

Indexing hint: Randomized controlled trial · 2019

6 results

Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial.

Rodbard et al. 2019Diabetes carecited by 343

PMID 31530666DOI 10.2337/dc19-0883PUB-31530666

Full text at the publisher6 results
Publisher pageSee results (6)

More studies

6 studies on this page

PubMed tag: none · 2023

Cost-Effectiveness of Semaglutide vs. Empagliflozin, Canagliflozin, and Sitagliptin for Treatment of Patients with Type 2 Diabetes in Denmark: A Decision-Analytic Modelling Study.

Pulleyblank et al. 2023PharmacoEconomics - opencited by 1

PMID 37178435PMC10333151DOI 10.1007/s41669-023-00416-zPUB-37178435

Free to read · publisher termsCC BY-NC
Read at source

PubMed tag: none · 2022

Long-Term Cost Effectiveness of Oral Semaglutide Versus Empagliflozin and Sitagliptin for the Treatment of Type 2 Diabetes in the Swedish Setting.

Eliasson et al. 2022PharmacoEconomics - opencited by 9

PMID 35064550PMC9043066DOI 10.1007/s41669-021-00317-zPUB-35064550

Free to read · publisher termsCC BY-NC
Read at source

PubMed tag: none · 2022

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme.

Aroda et al. 2022Diabetes, obesity & metabolismcited by 32

PMID 35373893PMC9321749DOI 10.1111/dom.14710PUB-35373893

Free to read · publisher termsCC BY-NC
Read at source

PubMed tag: none · 2022

Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials.

Mosenzon et al. 2022Cardiovascular diabetologycited by 65

PMID 36056351PMC9440529DOI 10.1186/s12933-022-01585-7PUB-36056351

CC BY
Download PDF

PubMed tag: none · 2020

Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk.

Husain et al. 2020Diabetes, obesity & metabolismcited by 154

PMID 31903692PMC7064975DOI 10.1111/dom.13955PUB-31903692

Free to read · publisher termsCC BY-NC
Read at source

Indexing hint: Review · 2020

Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme.

Thethi et al. 2020Diabetes, obesity & metabolismcited by 98

PMID 32267058PMC7384149DOI 10.1111/dom.14054PUB-32267058

Free to read · publisher termsCC BY-NC
Read at source

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial * Male or female, age above or equal to 18 years at the time of signing informed consent * Diagnosed with type 2 diabetes mellitus at least 90 days prior to day of screening * HbA1c (glycosylated haemoglobin) of 7.0-10.5 % (53-91 mmol/mol) (both inclusive) * Stable daily dose of metformin (at least 1500 mg or maximum tolerated dose as documented in the subject medical record) at least 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 an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice).For certain specific countries: Additional specific requirements apply * Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol * Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma * 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 hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening * Subjects presently classified as being in New York Heart Association Class IV * Planned coronary, carotid or peripheral artery revascularisation known on the day of screening * Subjects with ALT (alanine aminotransferase) above 2.5 x upper normal limit * Renal impairment defined as Estimated Glomerular Filtration Rate below 60 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) * Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 14 days * Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation * History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ) * History of diabetic ketoacidosis

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