Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus.

NCT ID: NCT02849080

Last Updated: 2022-07-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

504 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-20

Study Completion Date

2019-03-27

Brief Summary

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This trial is globally conducted. The aim of this trial is to investigate Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation versus Sitagliptin in Subjects with Type 2 Diabetes Mellitus.

Detailed Description

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Conditions

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Diabetes Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Semaglutide flexible dosing (3, 7 or 14 mg)

Group Type EXPERIMENTAL

semaglutide

Intervention Type DRUG

Oral administration once-daily.

Sitagliptin 100 mg

Group Type ACTIVE_COMPARATOR

sitagliptin

Intervention Type DRUG

Oral administration once-daily.

Interventions

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semaglutide

Oral administration once-daily.

Intervention Type DRUG

sitagliptin

Oral administration once-daily.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
* Male or female, age above or equal to 18 years at the time of signing informed consent. For Korea only: Male or female, age above or equal to 19 years at the time of signing informed consent
* Diagnosed with type 2 diabetes mellitus for at least 90 days prior to day of screening
* HbA1c (glycosylated haemoglobin) 7.5-9.5% (58-80 mmol/mol) (both inclusive)
* Treatment target of HbA1c below 7.0% (53 mmol/mol), as judged by the investigator
* Stable daily dose(s) of 1-2 of the following anti-diabetic drugs within 90 days prior to the day of screening:
* Metformin (equal or above 1500 mg or maximum tolerated dose as documented in the subject medical record)
* Sulfonylureas (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)
* Sodium glucose co-transporter 2 inhibitors
* Thiazolidinediones (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)

Extension phase:

* Informed consent for the extension phase obtained before any trial-related activities for the extension phase.
* On randomised treatment with or without rescue medication at week 52.

* 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

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 and randomisation
* 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 alanine aminotransferase above 2.5 x upper normal limit
* Renal impairment defined as Estimated Glomerular Filtration rate 60 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novo Nordisk A/S

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Novo Nordisk Investigational Site

Glendale, Arizona, United States

Site Status

Novo Nordisk Investigational Site

Phoenix, Arizona, United States

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Lancaster, California, United States

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West Hills, California, United States

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Boynton Beach, Florida, United States

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Lake Worth, Florida, United States

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Miami Lakes, Florida, United States

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Port Orange, Florida, United States

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Tampa, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Blackfoot, Idaho, United States

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Evanston, Illinois, United States

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Greenfield, Indiana, United States

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Muncie, Indiana, United States

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Louisville, Kentucky, United States

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Metairie, Louisiana, United States

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Oxon Hill, Maryland, United States

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Flint, Michigan, United States

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Billings, Montana, United States

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Henderson, Nevada, United States

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Albuquerque, New Mexico, United States

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Chapel Hill, North Carolina, United States

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Greensboro, North Carolina, United States

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Greenville, North Carolina, United States

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Whiteville, North Carolina, United States

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Cleveland, Ohio, United States

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Mentor, Ohio, United States

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Wadsworth, Ohio, United States

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Pittsburgh, Pennsylvania, United States

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Murrells Inlet, South Carolina, United States

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Myrtle Beach, South Carolina, United States

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Kingsport, Tennessee, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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Chesapeake, Virginia, United States

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Renton, Washington, United States

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CABA, , Argentina

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Corrientes, , Argentina

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Rosario, , Argentina

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Graz, , Austria

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Saint Stefan, , Austria

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Vienna, , Austria

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Bonheiden, , Belgium

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Boussu, , Belgium

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Brussels, , Belgium

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Edegem, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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São Paulo, São Paulo, Brazil

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Alexandria, , Egypt

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Cairo, , Egypt

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Cairo, , Egypt

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Hamar, , Norway

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Oslo, , Norway

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Oslo, , Norway

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Stavanger, , Norway

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Trondheim, , Norway

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Gangwon-do, , South Korea

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Gyeonggi-do, , South Korea

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Pusan, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Suwon, , South Korea

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Bern, , Switzerland

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Einsiedeln, , Switzerland

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Geneva, , Switzerland

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Lucerne, , Switzerland

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Olten, , Switzerland

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Sankt Gallen, , Switzerland

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Sankt Gallen, , Switzerland

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Winterthur, , Switzerland

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Antalya, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Novo Nordisk Investigational Site

Rize, , Turkey (Türkiye)

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Countries

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United States Argentina Austria Belgium Brazil Egypt Norway South Korea Switzerland Turkey (Türkiye)

References

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Pieber TR, Bode B, Mertens A, Cho YM, Christiansen E, Hertz CL, Wallenstein SOR, Buse JB; PIONEER 7 investigators. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019 Jul;7(7):528-539. doi: 10.1016/S2213-8587(19)30194-9. Epub 2019 Jun 9.

Reference Type RESULT
PMID: 31189520 (View on PubMed)

Buse JB, Bode BW, Mertens A, Cho YM, Christiansen E, Hertz CL, Nielsen MA, Pieber TR; PIONEER 7 investigators. Long-term efficacy and safety of oral semaglutide and the effect of switching from sitagliptin to oral semaglutide in patients with type 2 diabetes: a 52-week, randomized, open-label extension of the PIONEER 7 trial. BMJ Open Diabetes Res Care. 2020 Dec;8(2):e001649. doi: 10.1136/bmjdrc-2020-001649.

Reference Type RESULT
PMID: 33318068 (View on PubMed)

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.

Reference Type RESULT
PMID: 35373893 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33660198 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32998732 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32267058 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31903692 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://novonordisk-trials.com

Clinical Trials at Novo Nordisk

Other Identifiers

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2015-005593-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1177-5103

Identifier Type: OTHER

Identifier Source: secondary_id

NN9924-4257

Identifier Type: -

Identifier Source: org_study_id

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