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

NCT ID: NCT02607865

Last Updated: 2022-07-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1864 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-15

Study Completion Date

2018-03-28

Brief Summary

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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.

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

DOUBLE

Participants Investigators

Study Groups

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Semaglutide 3 mg

Group Type EXPERIMENTAL

semaglutide

Intervention Type DRUG

Oral administration once-daily

placebo

Intervention Type DRUG

Oral administration once-daily

Semaglutide 7 mg

Group Type EXPERIMENTAL

semaglutide

Intervention Type DRUG

Oral administration once-daily

placebo

Intervention Type DRUG

Oral administration once-daily

Semaglutide 14 mg

Group Type EXPERIMENTAL

semaglutide

Intervention Type DRUG

Oral administration once-daily

placebo

Intervention Type DRUG

Oral administration once-daily

Sitagliptin 100 mg

Group Type ACTIVE_COMPARATOR

sitagliptin

Intervention Type DRUG

Oral administration once-daily

placebo

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

placebo

Oral administration once-daily

Intervention Type DRUG

Eligibility Criteria

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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)
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

Anniston, Alabama, United States

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Countries

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United States Argentina Brazil France Germany India Israel Japan Mexico Romania Russia South Africa Turkey (Türkiye) Ukraine United Kingdom

References

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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.

Reference Type RESULT
PMID: 30903796 (View on PubMed)

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.

Reference Type RESULT
PMID: 34472698 (View on PubMed)

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.

Reference Type RESULT
PMID: 35064550 (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)

Pulleyblank R, Larsen NB. Cost-Effectiveness of Semaglutide vs. Empagliflozin, Canagliflozin, and Sitagliptin for Treatment of Patients with Type 2 Diabetes in Denmark: A Decision-Analytic Modelling Study. Pharmacoecon Open. 2023 Jul;7(4):579-591. doi: 10.1007/s41669-023-00416-z. Epub 2023 May 13.

Reference Type DERIVED
PMID: 37178435 (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

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Other Identifiers

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2015-001351-71

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1168-4339

Identifier Type: OTHER

Identifier Source: secondary_id

JAPIC

Identifier Type: OTHER

Identifier Source: secondary_id

NN9924-4222

Identifier Type: -

Identifier Source: org_study_id

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