Efficacy and Safety of Semaglutide Once Weekly Versus Insulin Glargine Once Daily as add-on to Metformin With or Without Sulphonylurea in Insulin-naïve Subjects With Type 2 Diabetes

NCT ID: NCT02128932

Last Updated: 2019-06-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1089 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-08-04

Study Completion Date

2015-09-03

Brief Summary

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This trial is conducted in Africa, North and South America, Asia and Europe. The purpose of the trial is to compare the effect of once-weekly dosing of two dose levels of semaglutide versus insulin glargine once-daily on glycaemic control after 30 weeks of treatment in insulin-naïve 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

NONE

Study Groups

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Semaglutide 0.5 mg/week

Group Type EXPERIMENTAL

semaglutide

Intervention Type DRUG

Injected subcutaneously (under the skin) once weekly. Following 4 doses (4 weeks) of 0.25 mg semaglutide weekly subjects will receive 0.5 mg semaglutide weekly for 26 weeks.

Semaglutide 1.0 mg/week

Group Type EXPERIMENTAL

semaglutide

Intervention Type DRUG

Injected subcutaneously (under the skin) once weekly. Following 4 doses (4 weeks) of 0.25 mg semaglutide weekly subjects will receive 0.5 mg semaglutide weekly for 26 weeks.

Insulin glargine

Group Type ACTIVE_COMPARATOR

insulin glargine

Intervention Type DRUG

Injected subcutaneously (under the skin) once daily. Subjects will start on 10 IU once daily and the dose will be adjusted according to fasting plasma glucose.

Interventions

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semaglutide

Injected subcutaneously (under the skin) once weekly. Following 4 doses (4 weeks) of 0.25 mg semaglutide weekly subjects will receive 0.5 mg semaglutide weekly for 26 weeks.

Intervention Type DRUG

insulin glargine

Injected subcutaneously (under the skin) once daily. Subjects will start on 10 IU once daily and the dose will be adjusted according to fasting plasma glucose.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male or female, 18 years or older at the time of signing informed consent
* Insulin-naïve subjects diagnosed with type 2 diabetes and on stable diabetes treatment with metformin or metformin and SU (metformin 1500 mg or higher or maximum tolerated dose and SU half of maximum allowed dose according to national label or higher) for at least 90 days before screening. Stable is defined as unchanged medication and unchanged dose
* HbA1c 7.0 - 10.0% (53 - 86 mmol/mol) both inclusive

* History of chronic or idiopathic acute pancreatitis
* Screening calcitonin value greater than or equal to 50 ng/L
* Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome 2
* Severe renal impairment defined as estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m\^2 per modification of diet in renal disease (MDRD) formula (4 variable version)
* Acute coronary or cerebrovascular event within 90 days before randomisation
* Heart failure, New York Heart Association Class IV
* Known proliferative retinopathy or maculopathy requiring acute treatment according to the opinion of the investigator
* Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer)
* Mental inability, unwillingness or language barrier precluding adequate understanding of or compliance with study procedures

Exclusion Criteria

* Female who is pregnant, breast-feeding or intends to become pregnant or of childbearing potential not using adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice) throughout the trial including the 5 week follow-up period
* Any disorder which, in the opinion of the Investigator might jeopardise subject's safety or compliance with the protocol
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

Principal Investigators

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Global Clinical Registry (GCR, 1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

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Birmingham, Alabama, United States

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Taunton, , United Kingdom

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Countries

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United States Argentina Croatia France Germany India Mexico Netherlands North Macedonia Puerto Rico Romania Slovakia Slovenia South Africa United Kingdom

References

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Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HbA1C >/=1.0% AND WEIGHT >/=5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. Endocr Pract. 2019 Jun;25(6):589-597. doi: 10.4158/EP-2018-0444. Epub 2019 Mar 13.

Reference Type BACKGROUND
PMID: 30865526 (View on PubMed)

Aroda VR, Bain SC, Cariou B, Piletic M, Rose L, Axelsen M, Rowe E, DeVries JH. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol. 2017 May;5(5):355-366. doi: 10.1016/S2213-8587(17)30085-2. Epub 2017 Mar 23.

Reference Type RESULT
PMID: 28344112 (View on PubMed)

Kapitza C, Dahl K, Jacobsen JB, Axelsen MB, Flint A. Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial. Diabetologia. 2017 Aug;60(8):1390-1399. doi: 10.1007/s00125-017-4289-0. Epub 2017 May 19.

Reference Type RESULT
PMID: 28526920 (View on PubMed)

Warren M, Chaykin L, Trachtenbarg D, Nayak G, Wijayasinghe N, Cariou B. Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials. Diabetes Obes Metab. 2018 Sep;20(9):2291-2297. doi: 10.1111/dom.13331. Epub 2018 Jun 7.

Reference Type RESULT
PMID: 29687620 (View on PubMed)

Ahren B, Atkin SL, Charpentier G, Warren ML, Wilding JPH, Birch S, Holst AG, Leiter LA. Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. Diabetes Obes Metab. 2018 Sep;20(9):2210-2219. doi: 10.1111/dom.13353. Epub 2018 Jun 12.

Reference Type RESULT
PMID: 29766634 (View on PubMed)

DeVries JH, Desouza C, Bellary S, Unger J, Hansen OKH, Zacho J, Woo V. Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. Diabetes Obes Metab. 2018 Oct;20(10):2426-2434. doi: 10.1111/dom.13396. Epub 2018 Jul 9.

Reference Type RESULT
PMID: 29862621 (View on PubMed)

Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jodar E, Mehta R, Woo V, Lingvay I. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Diabetes Metab. 2019 Oct;45(5):409-418. doi: 10.1016/j.diabet.2018.12.001. Epub 2019 Jan 4.

Reference Type RESULT
PMID: 30615985 (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)

Capehorn M, Ghani Y, Hindsberger C, Johansen P, Jodar E. Once-Weekly Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Common OAD: a Subgroup Analysis from SUSTAIN 2-4 and 10. Diabetes Ther. 2020 May;11(5):1061-1075. doi: 10.1007/s13300-020-00796-z. Epub 2020 Mar 19.

Reference Type DERIVED
PMID: 32193837 (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)

DeSouza C, Cariou B, Garg S, Lausvig N, Navarria A, Fonseca V. Efficacy and Safety of Semaglutide for Type 2 Diabetes by Race and Ethnicity: A Post Hoc Analysis of the SUSTAIN Trials. J Clin Endocrinol Metab. 2020 Feb 1;105(2):dgz072. doi: 10.1210/clinem/dgz072.

Reference Type DERIVED
PMID: 31769496 (View on PubMed)

Jendle J, Birkenfeld AL, Polonsky WH, Silver R, Uusinarkaus K, Hansen T, Hakan-Bloch J, Tadayon S, Davies MJ. Improved treatment satisfaction in patients with type 2 diabetes treated with once-weekly semaglutide in the SUSTAIN trials. Diabetes Obes Metab. 2019 Oct;21(10):2315-2326. doi: 10.1111/dom.13816. Epub 2019 Jul 12.

Reference Type DERIVED
PMID: 31215727 (View on PubMed)

Related Links

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http://novonordisk-trials.com

Clinical Trials at Novo Nordisk

Other Identifiers

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2013-004392-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1146-0211

Identifier Type: OTHER

Identifier Source: secondary_id

NL47781.018.14

Identifier Type: REGISTRY

Identifier Source: secondary_id

NN9535-3625

Identifier Type: -

Identifier Source: org_study_id

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