A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide and Insulin Degludec in Subjects With Type 2 Diabetes (DUAL™ II)

A 26-week Randomised, Parallel Two-arm, Double-blind, Multi-centre, Multinational, Treat-to-target Trial Comparing Fixed Ratio Combination of Insulin Degludec and Liraglutide With Insulin Degludec in Subjects With Type 2 Diabetes

This trial is conducted in Asia, Europe and the United States of America (USA). The aim of this trial is to compare the efficacy and safety of insulin degludec/liraglutide (IDegLira) and insulin degludec (IDeg) in subjects with type 2 diabetes. Subjects continue their pre-trial treatment with metformin throughout the entire trial.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: insulin degludec/liraglutide; Drug: insulin degludec

• Study Type: Interventional
• Enrollment (Actual): 413
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Burgas, Bulgaria, 8000
    • Novo Nordisk Investigational Site
  • Haskovo, Bulgaria, 6300
    • Novo Nordisk Investigational Site
  • Lukovit, Bulgaria, 5770
    • Novo Nordisk Investigational Site
  • Plovdiv, Bulgaria, 4001
    • Novo Nordisk Investigational Site
  • Ruse, Bulgaria, 7000
    • Novo Nordisk Investigational Site
  • Sofia, Bulgaria, 1712
    • Novo Nordisk Investigational Site
• Denmark
  • Gentofte, Denmark, 2820
    • Novo Nordisk Investigational Site
  • Hellerup, Denmark, 2900
    • Novo Nordisk Investigational Site
  • Århus C, Denmark, 8000
    • Novo Nordisk Investigational Site
• Hungary
  • Budapest, Hungary, 1125
    • Novo Nordisk Investigational Site
  • Debrecen, Hungary, 4043
    • Novo Nordisk Investigational Site
  • Eger, Hungary, H-3300
    • Novo Nordisk Investigational Site
  • Szombathely, Hungary, H-9700
    • Novo Nordisk Investigational Site
• India
  • Dhantoli, Nagpur, India, 440012
    • Novo Nordisk Investigational Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • Novo Nordisk Investigational Site
    • Mumbai, Maharashtra, India, 400053
      • Novo Nordisk Investigational Site
    • Pune, Maharashtra, India, 411001.
      • Novo Nordisk Investigational Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600086
      • Novo Nordisk Investigational Site
  • West Bengal
    • Kolkata, West Bengal, India, 700064
      • Novo Nordisk Investigational Site
• Slovenia
  • Koper, Slovenia, SI-6000
    • Novo Nordisk Investigational Site
  • Ljubljana, Slovenia, 1525
    • Novo Nordisk Investigational Site
  • Novo mesto, Slovenia, 8000
    • Novo Nordisk Investigational Site
• Switzerland
  • Basel, Switzerland, 4031
    • Novo Nordisk Investigational Site
  • Bern, Switzerland, 3010
    • Novo Nordisk Investigational Site
  • Interlaken-Unterseen, Switzerland, 3800
    • Novo Nordisk Investigational Site
  • Lausanne, Switzerland, 1011
    • Novo Nordisk Investigational Site
  • Luzern 16, Switzerland, 6000
    • Novo Nordisk Investigational Site
  • St. Gallen, Switzerland, 9007
    • Novo Nordisk Investigational Site
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Novo Nordisk Investigational Site
    • Vestavia Hills, Alabama, United States, 35209
      • Novo Nordisk Investigational Site
  • California
    • Anaheim, California, United States, 92801
      • Novo Nordisk Investigational Site
    • Los Angeles, California, United States, 90057
      • Novo Nordisk Investigational Site
    • Tustin, California, United States, 92780
      • Novo Nordisk Investigational Site
    • Ventura, California, United States, 93003
      • Novo Nordisk Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • Novo Nordisk Investigational Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Novo Nordisk Investigational Site
  • Florida
    • Melbourne, Florida, United States, 32934
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33156
      • Novo Nordisk Investigational Site
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Novo Nordisk Investigational Site
  • Illinois
    • Arlington Heights, Illinois, United States, 60004-2315
      • Novo Nordisk Investigational Site
    • Avon, Illinois, United States, 46123
      • Novo Nordisk Investigational Site
    • Chicago, Illinois, United States, 60607
      • Novo Nordisk Investigational Site
    • Crystal Lake, Illinois, United States, 60012
      • Novo Nordisk Investigational Site
    • Gurnee, Illinois, United States, 60031
      • Novo Nordisk Investigational Site
  • Indiana
    • Greenfield, Indiana, United States, 46140
      • Novo Nordisk Investigational Site
    • Indianapolis, Indiana, United States, 46254
      • Novo Nordisk Investigational Site
    • Muncie, Indiana, United States, 47304
      • Novo Nordisk Investigational Site
    • New Albany, Indiana, United States, 47150
      • Novo Nordisk Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Novo Nordisk Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70002
      • Novo Nordisk Investigational Site
    • Metairie, Louisiana, United States, 70006-2930
      • Novo Nordisk Investigational Site
    • Slidell, Louisiana, United States, 70461-4231
      • Novo Nordisk Investigational Site
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Novo Nordisk Investigational Site
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • Novo Nordisk Investigational Site
    • North Dartmouth, Massachusetts, United States, 02747
      • Novo Nordisk Investigational Site
    • Waltham, Massachusetts, United States, 02453
      • Novo Nordisk Investigational Site
  • Michigan
    • Southfield, Michigan, United States, 48034-7661
      • Novo Nordisk Investigational Site
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Novo Nordisk Investigational Site
    • Saint Charles, Missouri, United States, 63303
      • Novo Nordisk Investigational Site
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Novo Nordisk Investigational Site
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Novo Nordisk Investigational Site
    • Toms River, New Jersey, United States, 08755-8050
      • Novo Nordisk Investigational Site
  • New York
    • Albany, New York, United States, 12206
      • Novo Nordisk Investigational Site
    • Smithtown, New York, United States, 11787
      • Novo Nordisk Investigational Site
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Novo Nordisk Investigational Site
    • Chapel Hill, North Carolina, United States, 27517
      • Novo Nordisk Investigational Site
    • Greensboro, North Carolina, United States, 27408
      • Novo Nordisk Investigational Site
    • Hickory, North Carolina, United States, 28602
      • Novo Nordisk Investigational Site
    • Statesville, North Carolina, United States, 28625
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Novo Nordisk Investigational Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Novo Nordisk Investigational Site
    • Philadelphia, Pennsylvania, United States, 19152
      • Novo Nordisk Investigational Site
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Novo Nordisk Investigational Site
    • Simpsonville, South Carolina, United States, 29681
      • Novo Nordisk Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Novo Nordisk Investigational Site
  • Texas
    • Arlington, Texas, United States, 76014
      • Novo Nordisk Investigational Site
    • Austin, Texas, United States, 78731
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75246
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75251
      • Novo Nordisk Investigational Site
    • Hurst, Texas, United States, 76054
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78229
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78215
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78224
      • Novo Nordisk Investigational Site
    • Sugar Land, Texas, United States, 77478
      • Novo Nordisk Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with type 2 diabetes
• HbA1c (glycosylated haemoglobin) 7.5-10.0% (both inclusive)
• Subjects on stable daily doses for at least 90 days prior to trial start of: Basal insulin (total daily basal insulin dose within the range of 20-40U in combination with: metformin (1500 mg or more or max. tolerated dose) or metformin (1500 mg or more or max. tolerated dose) and SU (sulfonylurea) (equal to or more than half of the max. approved dose according to local label) or metformin and glinides (equal to or more than half of the max. approved dose according to local label)
• BMI (Body Mass Index) more than or equal to 27 kg/m^2

Exclusion Criteria:

• Treatment with glucagon like peptide-1 (GLP-1) receptor agonists (e.g. exenatide, liraglutide), dipeptidyl peptidase 4 (DPP-4) inhibitors and/or thiazolidinediones within 90 days prior to trial start
• Impaired liver function
• Impaired renal function
• Screening calcitonin equal to or above 50 ng/l
• Subjects with personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2)
• Cardiac disorder defined as: congestive heart failure (NYHA class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the last 52 weeks prior to trial start and/or planned coronary, carotid or peripheral artery revascularisation procedures
• Severe uncontrolled treated or untreated hypertension (systolic blood pressure equal to or above 180 mm Hg or diastolic blood pressure equal to or above 100 mm Hg)
• Acute treatment required proliferative retinopathy or maculopathy (macular oedema) according to physician's opinion
• History of chronic pancreatitis or idiopathic acute pancreatitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IDegLira + metformin; IDegLira was injected subcutaneously once daily for 26 weeks.	Drug: insulin degludec/liraglutide; IDeg/Lira treatment will be initiated and titrated (individually adjusted) twice weekly according to the mean self measured plasma glucose (SMPG) (fasting). IDegLira is injected subcutaneously (under the skin) once daily.
Experimental: IDeg + metformin; IDeg was injected subcutaneously once daily for 26 weeks.	Drug: insulin degludec; IDeg treatment will be initiated and titrated (individually adjusted) twice weekly according to the mean self measured plasma glucose (SMPG) (fasting). IDeg is injected subcutaneously (under the skin) once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c (Glycosylated Haemoglobin)	Observed mean change from baseline in HbA1c after 26 Weeks of treatment.	Week 0, week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight	Observed mean change from baseline in body weight after 26 Weeks of treatment.	Week 0, week 26

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Khunti K, Mohan V, Jain SM, Boesgaard TW, Begtrup K, Sethi B. Efficacy and Safety of IDegLira in Participants with Type 2 Diabetes in India Uncontrolled on Oral Antidiabetic Drugs and Basal Insulin: Data from the DUAL Clinical Trial Program. Diabetes Ther. 2017 Jun;8(3):673-682. doi: 10.1007/s13300-017-0252-9. Epub 2017 Mar 22.
• Vilsboll T, Vora J, Jarlov H, Kvist K, Blonde L. Type 2 Diabetes Patients Reach Target Glycemic Control Faster Using IDegLira than Either Insulin Degludec or Liraglutide Given Alone. Clin Drug Investig. 2016 Apr;36(4):293-303. doi: 10.1007/s40261-016-0376-0.
• King AB, Philis-Tsimikas A, Kilpatrick ES, Langbakke IH, Begtrup K, Vilsboll T. A Fixed Ratio Combination of Insulin Degludec and Liraglutide (IDegLira) Reduces Glycemic Fluctuation and Brings More Patients with Type 2 Diabetes Within Blood Glucose Target Ranges. Diabetes Technol Ther. 2017 Apr;19(4):255-264. doi: 10.1089/dia.2016.0405. Epub 2017 Mar 10.
• Lingvay I, Handelsman Y, Linjawi S, Vilsboll T, Halladin N, Ranc K, Liebl A. EFFICACY AND SAFETY OF IDEGLIRA IN OLDER PATIENTS WITH TYPE 2 DIABETES. Endocr Pract. 2019 Feb;25(2):144-155. doi: 10.4158/EP-2018-0284. Epub 2018 Nov 1.
• Ericsson A, Lundqvist A. Cost Effectiveness of Insulin Degludec Plus Liraglutide (IDegLira) in a Fixed Combination for Uncontrolled Type 2 Diabetes Mellitus in Sweden. Appl Health Econ Health Policy. 2017 Apr;15(2):237-248. doi: 10.1007/s40258-016-0301-y.
• Buse JB, Vilsboll T, Thurman J, Blevins TC, Langbakke IH, Bottcher SG, Rodbard HW; NN9068-3912 (DUAL-II) Trial Investigators. Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira). Diabetes Care. 2014 Nov;37(11):2926-33. doi: 10.2337/dc14-0785. Epub 2014 Aug 11.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 4, 2012

Study Registration Dates

• First Submitted: July 7, 2011
• First Submitted That Met QC Criteria: July 11, 2011
• First Posted (Estimate): July 12, 2011

Study Record Updates

• Last Update Posted (Actual): January 3, 2019
• Last Update Submitted That Met QC Criteria: December 7, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Insulin; Insulin, Globin Zinc; Insulin, Long-Acting; Liraglutide; Xultophy
• Other Study ID Numbers: NN9068-3912; 2011-002336-72 (EudraCT Number); U1111-1121-4897 (Other Identifier: WHO)