The Efficacy and Safety of Liraglutide Adjunct to Insulin Treatment in Type 1 Diabetes

NCT ID: NCT02098395

Last Updated: 2017-02-09

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

835 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-31

Study Completion Date

2015-04-30

Brief Summary

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This trial is conducted in Africa, Europe and North America. The purpose of the trial is to investigate the efficacy and safety of liraglutide adjunct to insulin treatment in type 1 diabetes.

Detailed Description

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Conditions

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Diabetes Diabetes Mellitus, Type 1

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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Liraglutide 1.8 mg + insulin

Group Type EXPERIMENTAL

liraglutide

Intervention Type DRUG

Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

Liraglutide 1.2 mg + insulin

Group Type EXPERIMENTAL

liraglutide

Intervention Type DRUG

Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

Liraglutide 0.6 mg + insulin

Group Type EXPERIMENTAL

liraglutide

Intervention Type DRUG

Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

Liraglutide placebo 0.3 ml + insulin

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

Liraglutide placebo 0.2 ml + insulin

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

Liraglutide placebo 0.1 ml + insulin

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

Interventions

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liraglutide

Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

Intervention Type DRUG

liraglutide

Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

Intervention Type DRUG

liraglutide

Subjects randomised to 1.8 mg liraglutide treatment as an add-on to their pre-trial insulin treatment will receive 0.6 mg liraglutide for 2 weeks followed by 1.2 mg liraglutide for 2 weeks. After 4 weeks of treatment subjects will receive 1.8 mg liraglutide for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

Intervention Type DRUG

placebo

Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

Intervention Type DRUG

placebo

Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) once daily.

Intervention Type DRUG

placebo

Subjects randomised to 0.3 mL liraglutide placebo as an add-on to their pre-trial insulin treatment will receive 0.1 mL for 2 weeks followed by 0.2 mL for 2 weeks. After 4 weeks of liraglutide placebo, subjects will receive 0.3 mL for 22 weeks. Administered subcutaneously (s.c., under the skin) 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, aged equal to or greater than 18 years at the time of signing informed consent
* Type 1 diabetes mellitus (as diagnosed clinically) 12 months or longer prior to Visit 1 (i.e. screening)
* Treatment with basal bolus or CSII (continuous subcutaneous insulin infusion, insulin pump) treatment 6 months or longer prior to Visit 1 (i.e. screening)
* Stable insulin treatment 3 months or longer prior to Visit 1 (i.e. screening), as judged and documented by the investigator
* HbA1c 7.0-10.0 percent (Diabetes Control and Complications Trial (DCCT)), both inclusive, by central laboratory analysis (Visit 1, screening) corresponding to 53-86 mmol/mol (International Federation of Clinical Chemistry (IFCC))

Exclusion Criteria

* Prior use of glucagon-like peptide-1 (GLP-1) receptor agonist or dipeptidyl peptidase IV (DPPIV) inhibitors
* Use of any medication, which in the investigator's opinion could interfere with the glycaemic control (e.g. systemic corticosteroids, pramlintide (Symlin®)) or affect the subject's safety. Premix insulin is not allowed
* Known proliferative retinopathy or maculopathy requiring acute treatment
* Severe neuropathy, in particular autonomic neuropathy, i.e. gastroparesis, as judged by the investigator
* Uncontrolled/untreated blood pressure at screening (Visit 1) (after resting for 5 minutes) while sitting greater than 160 mmHg for systolic or greater than 100 mmHg for diastolic (repeated measurement at Visit 2 (prior to performing the trial related activities) is allowed to exclude white-coat hypertension)
* History of acute or chronic pancreatitis
* Screening (Visit 1) calcitonin value equal to or greater than 50 ng/L
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 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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Novo Nordisk Investigational Site

Phoenix, Arizona, United States

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Little Rock, Arkansas, United States

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Concord, California, United States

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Escondido, California, United States

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Fresno, California, United States

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Montclair, California, United States

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San Mateo, California, United States

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San Ramon, California, United States

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Ventura, California, United States

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Walnut Creek, California, United States

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Aurora, Colorado, United States

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Golden, Colorado, United States

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Maitland, Florida, United States

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Atlanta, Georgia, United States

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Marietta, Georgia, United States

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Roswell, Georgia, United States

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Champaign, Illinois, United States

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Chicago, Illinois, United States

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Skokie, Illinois, United States

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Council Bluffs, Iowa, United States

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Lexington, Kentucky, United States

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Rockville, Maryland, United States

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Minneapolis, Minnesota, United States

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Chesterfield, Missouri, United States

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Billings, Montana, United States

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Butte, Montana, United States

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Las Vegas, Nevada, United States

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Albany, New York, United States

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Jamaica, New York, United States

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Staten Island, New York, United States

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Chapel Hill, North Carolina, United States

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Morehead City, North Carolina, United States

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Wilmington, North Carolina, United States

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Fargo, North Dakota, United States

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Bristol, Tennessee, United States

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Chattanooga, Tennessee, United States

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Amarillo, Texas, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Round Rock, Texas, United States

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Murray, Utah, United States

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Ogden, Utah, United States

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Bennington, Vermont, United States

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Federal Way, Washington, United States

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Renton, Washington, United States

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Seattle, Washington, United States

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Graz, , Austria

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Vienna, , Austria

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Aalst, , Belgium

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Bonheiden, , Belgium

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Boussu, , Belgium

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Brussels, , Belgium

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Brussels, , Belgium

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Edegem, , Belgium

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Kortrijk, , Belgium

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Leuven, , Belgium

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Mouscron, , Belgium

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Sint-Niklaas, , Belgium

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Blagoevgrad, , Bulgaria

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Pazardzhik, , Bulgaria

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Plovdiv, , Bulgaria

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Razgrad, , Bulgaria

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Sofia, , Bulgaria

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Calgary, Alberta, Canada

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Halifax, Nova Scotia, Canada

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Cornwall, Ontario, Canada

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Hamilton, Ontario, Canada

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Mississauga, Ontario, Canada

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Thornhill, Ontario, Canada

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Laval, Quebec, Canada

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Montreal, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Århus C, , Denmark

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Copenhagen, , Denmark

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Hvidovre, , Denmark

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Odense, , Denmark

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Helsinki, , Finland

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Joensuu, , Finland

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Jyväskylä, , Finland

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Oulu, , Finland

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Pori, , Finland

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Turku, , Finland

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La Rochelle, , France

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Le Creusot, , France

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Marseille, , France

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Montpellier, , France

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Paris, , France

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Pierre-Bénite, , France

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Reims, , France

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Strasbourg, , France

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Toulouse, , France

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Trinité - La Martinique, , France

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Bergamo, , Italy

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Catanzaro, , Italy

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Florence, , Italy

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Palermo, , Italy

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Roma, , Italy

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Roma, , Italy

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Sesto San Giovanni (MI), , Italy

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Siena, , Italy

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's-Hertogenbosch, , Netherlands

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Amersfoort, , Netherlands

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Apeldoorn, , Netherlands

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Eindhoven, , Netherlands

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The Hague, , Netherlands

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Utrecht, , Netherlands

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Johannesburg, Gauteng, South Africa

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Cape Town, Western Cape, South Africa

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Almería, , Spain

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Gijón, , Spain

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Segovia, , Spain

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Seville, , Spain

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Seville, , Spain

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Ängelholm, , Sweden

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Linköping, , Sweden

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Malmo, , Sweden

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Örebro, , Sweden

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Stockholm, , Sweden

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Umeå, , Sweden

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Countries

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United States Austria Belgium Bulgaria Canada Denmark Finland France Italy Netherlands South Africa Spain Sweden

References

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Ahren B, Hirsch IB, Pieber TR, Mathieu C, Gomez-Peralta F, Hansen TK, Philotheou A, Birch S, Christiansen E, Jensen TJ, Buse JB; ADJUNCT TWO Investigators. Efficacy and Safety of Liraglutide Added to Capped Insulin Treatment in Subjects With Type 1 Diabetes: The ADJUNCT TWO Randomized Trial. Diabetes Care. 2016 Oct;39(10):1693-701. doi: 10.2337/dc16-0690. Epub 2016 Aug 4.

Reference Type RESULT
PMID: 27493132 (View on PubMed)

Hoogenhout M, Malcolm-Smith S. Theory of mind predicts severity level in autism. Autism. 2017 Feb;21(2):242-252. doi: 10.1177/1362361316636758. Epub 2016 Aug 19.

Reference Type RESULT
PMID: 27493232 (View on PubMed)

Shah VN, Agesen RM, Bardtrum L, Christiansen E, Snaith J, Greenfield JR. Determinants of Liraglutide Treatment Discontinuation in Type 1 Diabetes: A Post Hoc Analysis of ADJUNCT ONE and ADJUNCT TWO Randomized Placebo-Controlled Clinical Studies. J Diabetes Sci Technol. 2025 Mar;19(2):321-331. doi: 10.1177/19322968241305647. Epub 2024 Dec 24.

Reference Type DERIVED
PMID: 39717993 (View on PubMed)

Dejgaard TF, von Scholten BJ, Christiansen E, Kreiner FF, Bardtrum L, von Herrath M, Mathieu C, Madsbad S; ADJUNCT ONE and ADJUNCT TWO Investigators. Efficacy and safety of liraglutide in type 1 diabetes by baseline characteristics in the ADJUNCT ONE and ADJUNCT TWO randomized controlled trials. Diabetes Obes Metab. 2021 Dec;23(12):2752-2762. doi: 10.1111/dom.14532. Epub 2021 Sep 28.

Reference Type DERIVED
PMID: 34463425 (View on PubMed)

Related Links

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http://novonordisk-trials.com

Clinical Trials at Novo Nordisk

Other Identifiers

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2012-005778-74

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1138-0619

Identifier Type: OTHER

Identifier Source: secondary_id

NL47705.060.14

Identifier Type: REGISTRY

Identifier Source: secondary_id

REec-2014-0884

Identifier Type: REGISTRY

Identifier Source: secondary_id

NN9211-4083

Identifier Type: -

Identifier Source: org_study_id

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