Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01336023




Registration number
NCT01336023
Ethics application status
Date submitted
13/04/2011
Date registered
15/04/2011
Date last updated
19/02/2018

Titles & IDs
Public title
Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Subjects With Type 2 Diabetes
Scientific title
A 26 Week Randomised, Parallel Three-arm, Open-label, Multi-centre, Multinational Treat-to-target Trial Comparing Fixed Ratio Combination of Insulin Degludec and Liraglutide Versus Insulin Degludec or Liraglutide Alone, in Subjects With Type 2 Diabetes Treated With 1-2 Oral Anti-diabetic Drugs (OADs)With a 26 Week Extension
Secondary ID [1] 0 0
U1111-1119-1174
Secondary ID [2] 0 0
NN9068-3697
Universal Trial Number (UTN)
Trial acronym
DUAL™ I
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes 0 0
Diabetes Mellitus, Type 2 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - insulin degludec/liraglutide
Treatment: Drugs - insulin degludec
Treatment: Drugs - liraglutide

Experimental: IDeg -

Experimental: IDegLira -

Experimental: Lira -


Treatment: Drugs: insulin degludec/liraglutide
Insulin degludec/liraglutide treatment will be initiated and titrated (individually adjusted) twice weekly according to the mean self measured plasma glucose (SMPG) (fasting). Insulin degludec/liraglutide is injected subcutaneously (under the skin) once daily.

Treatment: Drugs: insulin degludec
Insulin degludec treatment will be initiated with 10 U and titrated (individually adjusted) twice weekly according to the mean SMPG (fasting). Insulin degludec is injected subcutaneously (under the skin) once daily.

Treatment: Drugs: liraglutide
Liraglutide will be started with 0.6 mg and subsequent 0.6 mg weekly dose escalation to 1.8 mg. Liraglutide dose of 1.8 mg/day will be continued for the remaining part of the trial. Liraglutide is injected subcutaneously (under the skin) once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline in HbA1c (Glycosylated Haemoglobin) at Week 26.
Timepoint [1] 0 0
Week 0, week 26
Secondary outcome [1] 0 0
Mean Change From Baseline in Body Weight at Week 26
Timepoint [1] 0 0
Week 0, Week 26
Secondary outcome [2] 0 0
Number of Hypoglycaemic Episodes
Timepoint [2] 0 0
Weeks 0-26
Secondary outcome [3] 0 0
Change From Baseline in Incremental Area Under the Curve 0-4h (iAUC0-4h) Derived From the Glucose Concentration Profile During Meal Test
Timepoint [3] 0 0
Week 0, Week 26
Secondary outcome [4] 0 0
Mean Actual Daily Insulin Dose
Timepoint [4] 0 0
Week 26

Eligibility
Key inclusion criteria
* Subjects with type 2 diabetes
* HbA1c 7.0-10.0 % (both inclusive) with the aim of a median HbA1c of 8.3%. Accordingly, when approximately 50% of the randomised subjects have a HbA1c above 8.3%, the remaining subjects randomised must have a HbA1c of below or equal to 8.3%, or when approximately 50% of the randomised subjects have a HbA1c of below or equal to 8.3%, the remaining subjects randomised must have a HbA1c above 8.3%
* Male or female, age 18 years or above (Taiwan: 20 years or above for a site 653 in Taiwan: Taichung Veterans General Hospital)
* Subjects on stable dose of 1-2 OADs (metformin [at least 1500 mg or max tolerated dose] or metformin [at least 1500 mg or max tolerated dose] + pioglitazone [at least 30 mg]) for at least 90 days prior to screening
* Body Mass Index (BMI) maximum 40 kg/m^2
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Treatment with insulin (except for short-term treatment due to intercurrent illness at the discretion of the Investigator)
* Treatment with GLP-1 (glucagon-like peptide-1) receptor agonists (eg exenatide, liraglutide), sulphonylurea or dipeptidyl peptidase 4 (DPP-4) inhibitors within 90 days prior to trial
* Impaired liver function, defined as alanine aminotransferese (ALAT) at least 2.5 times Upper Normal Range (UNR) (one retest analysed at the central laboratory within a week from first sample taken is permitted with the result of the last sample being the conclusive)
* Impaired renal function defined as serum-creatinine at least 133 mcmol/l (at least 1.5 mg/dl) for males and at least 125 mcmol/l (at least 1.4) for females, or as allowed according to local contraindications for metformin (one retest analysed at the central laboratory within a week from first sample taken is permitted with the result of the last sample being the conclusive)
* Screening calcitonin at least 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 12 months and planned coronary, carotid or peripheral artery revascularisation procedures
* Severe uncontrolled treated or untreated hypertension (systolic blood pressure at least 180 mm Hg or diastolic blood pressure at least 100 mm Hg)
* Acute treatment required proliferative retinopathy or maculopathy (macular oedema)
* History of chronic pancreatitis or idiopathic acute pancreatitis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/05/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/11/2012
Sample size
Target
Accrual to date
Final
1663
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Novo Nordisk Investigational Site - Broadmeadow
Recruitment hospital [2] 0 0
Novo Nordisk Investigational Site - Camperdown
Recruitment hospital [3] 0 0
Novo Nordisk Investigational Site - Coffs Harbour
Recruitment hospital [4] 0 0
Novo Nordisk Investigational Site - Penrith
Recruitment hospital [5] 0 0
Novo Nordisk Investigational Site - Meadowbrook
Recruitment hospital [6] 0 0
Novo Nordisk Investigational Site - Keswick
Recruitment hospital [7] 0 0
Novo Nordisk Investigational Site - East Ringwood
Recruitment hospital [8] 0 0
Novo Nordisk Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
2292 - Broadmeadow
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [4] 0 0
2751 - Penrith
Recruitment postcode(s) [5] 0 0
4131 - Meadowbrook
Recruitment postcode(s) [6] 0 0
5035 - Keswick
Recruitment postcode(s) [7] 0 0
3135 - East Ringwood
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Idaho
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Indiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Louisiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Maryland
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
Nevada
Country [17] 0 0
United States of America
State/province [17] 0 0
New Hampshire
Country [18] 0 0
United States of America
State/province [18] 0 0
New Jersey
Country [19] 0 0
United States of America
State/province [19] 0 0
New York
Country [20] 0 0
United States of America
State/province [20] 0 0
North Carolina
Country [21] 0 0
United States of America
State/province [21] 0 0
Ohio
Country [22] 0 0
United States of America
State/province [22] 0 0
Oklahoma
Country [23] 0 0
United States of America
State/province [23] 0 0
Pennsylvania
Country [24] 0 0
United States of America
State/province [24] 0 0
Rhode Island
Country [25] 0 0
United States of America
State/province [25] 0 0
South Carolina
Country [26] 0 0
United States of America
State/province [26] 0 0
Tennessee
Country [27] 0 0
United States of America
State/province [27] 0 0
Texas
Country [28] 0 0
United States of America
State/province [28] 0 0
Utah
Country [29] 0 0
United States of America
State/province [29] 0 0
Virginia
Country [30] 0 0
United States of America
State/province [30] 0 0
Washington
Country [31] 0 0
United States of America
State/province [31] 0 0
Wisconsin
Country [32] 0 0
Canada
State/province [32] 0 0
Alberta
Country [33] 0 0
Canada
State/province [33] 0 0
British Columbia
Country [34] 0 0
Canada
State/province [34] 0 0
Manitoba
Country [35] 0 0
Canada
State/province [35] 0 0
Ontario
Country [36] 0 0
Canada
State/province [36] 0 0
Quebec
Country [37] 0 0
Finland
State/province [37] 0 0
Hanko
Country [38] 0 0
Finland
State/province [38] 0 0
Helsinki
Country [39] 0 0
Finland
State/province [39] 0 0
Imatra
Country [40] 0 0
Finland
State/province [40] 0 0
Kokkola
Country [41] 0 0
Finland
State/province [41] 0 0
Oulu
Country [42] 0 0
Germany
State/province [42] 0 0
Bad Neuenahr-Ahrweiler
Country [43] 0 0
Germany
State/province [43] 0 0
Eisenach
Country [44] 0 0
Germany
State/province [44] 0 0
Esslingen
Country [45] 0 0
Germany
State/province [45] 0 0
Frankfurt
Country [46] 0 0
Germany
State/province [46] 0 0
Grevenbroich
Country [47] 0 0
Germany
State/province [47] 0 0
Hamburg
Country [48] 0 0
Germany
State/province [48] 0 0
Herrenberg
Country [49] 0 0
Germany
State/province [49] 0 0
Hohenmölsen
Country [50] 0 0
Germany
State/province [50] 0 0
Münster
Country [51] 0 0
Germany
State/province [51] 0 0
Oldenburg
Country [52] 0 0
Germany
State/province [52] 0 0
Pohlheim
Country [53] 0 0
Germany
State/province [53] 0 0
Rehburg-Loccum
Country [54] 0 0
Germany
State/province [54] 0 0
Rehlingen-Siersburg
Country [55] 0 0
Germany
State/province [55] 0 0
Stuttgart
Country [56] 0 0
Hungary
State/province [56] 0 0
Budapest
Country [57] 0 0
Hungary
State/province [57] 0 0
Debrecen
Country [58] 0 0
Hungary
State/province [58] 0 0
Eger
Country [59] 0 0
Hungary
State/province [59] 0 0
Gyula
Country [60] 0 0
Hungary
State/province [60] 0 0
Pécs
Country [61] 0 0
Hungary
State/province [61] 0 0
Szeged
Country [62] 0 0
India
State/province [62] 0 0
Gujarat
Country [63] 0 0
India
State/province [63] 0 0
Haryana
Country [64] 0 0
India
State/province [64] 0 0
Karnataka
Country [65] 0 0
India
State/province [65] 0 0
Kerala
Country [66] 0 0
India
State/province [66] 0 0
Madhya Pradesh
Country [67] 0 0
India
State/province [67] 0 0
Maharashtra
Country [68] 0 0
India
State/province [68] 0 0
Orissa
Country [69] 0 0
India
State/province [69] 0 0
Rajasthan
Country [70] 0 0
India
State/province [70] 0 0
Tamil Nadu
Country [71] 0 0
India
State/province [71] 0 0
West Bengal
Country [72] 0 0
India
State/province [72] 0 0
Hyderabad
Country [73] 0 0
India
State/province [73] 0 0
Kolkata
Country [74] 0 0
India
State/province [74] 0 0
Patna
Country [75] 0 0
India
State/province [75] 0 0
Pune
Country [76] 0 0
Ireland
State/province [76] 0 0
Dublin
Country [77] 0 0
Ireland
State/province [77] 0 0
Galway
Country [78] 0 0
Italy
State/province [78] 0 0
Cosenza
Country [79] 0 0
Italy
State/province [79] 0 0
Forlì
Country [80] 0 0
Italy
State/province [80] 0 0
Monserrato, Cagliari
Country [81] 0 0
Italy
State/province [81] 0 0
Novara
Country [82] 0 0
Italy
State/province [82] 0 0
Olbia
Country [83] 0 0
Italy
State/province [83] 0 0
Palermo
Country [84] 0 0
Italy
State/province [84] 0 0
Siena
Country [85] 0 0
Italy
State/province [85] 0 0
Torino
Country [86] 0 0
Malaysia
State/province [86] 0 0
Cheras
Country [87] 0 0
Malaysia
State/province [87] 0 0
Kota Bharu, Kelantan
Country [88] 0 0
Malaysia
State/province [88] 0 0
Penang
Country [89] 0 0
Malaysia
State/province [89] 0 0
Pulau Pinang
Country [90] 0 0
Malaysia
State/province [90] 0 0
Putrajaya
Country [91] 0 0
Malaysia
State/province [91] 0 0
Seremban
Country [92] 0 0
Mexico
State/province [92] 0 0
Jalisco
Country [93] 0 0
Mexico
State/province [93] 0 0
Nuevo León
Country [94] 0 0
Puerto Rico
State/province [94] 0 0
San Juan
Country [95] 0 0
Russian Federation
State/province [95] 0 0
Kursk
Country [96] 0 0
Russian Federation
State/province [96] 0 0
Moscow
Country [97] 0 0
Russian Federation
State/province [97] 0 0
Penza
Country [98] 0 0
Russian Federation
State/province [98] 0 0
Saint-Petersburg
Country [99] 0 0
Russian Federation
State/province [99] 0 0
Saratov
Country [100] 0 0
Russian Federation
State/province [100] 0 0
Stavropol
Country [101] 0 0
Russian Federation
State/province [101] 0 0
Voronezh
Country [102] 0 0
Russian Federation
State/province [102] 0 0
Vsevolozhsk
Country [103] 0 0
Singapore
State/province [103] 0 0
Singapore
Country [104] 0 0
Slovakia
State/province [104] 0 0
Bratislava
Country [105] 0 0
Slovakia
State/province [105] 0 0
Lucenec
Country [106] 0 0
Slovakia
State/province [106] 0 0
Moldava nad Bodvou
Country [107] 0 0
Slovakia
State/province [107] 0 0
Nove Zamky
Country [108] 0 0
South Africa
State/province [108] 0 0
Eastern Cape
Country [109] 0 0
South Africa
State/province [109] 0 0
Free State
Country [110] 0 0
South Africa
State/province [110] 0 0
Gauteng
Country [111] 0 0
South Africa
State/province [111] 0 0
KwaZulu-Natal
Country [112] 0 0
South Africa
State/province [112] 0 0
North West
Country [113] 0 0
South Africa
State/province [113] 0 0
Western Cape
Country [114] 0 0
Spain
State/province [114] 0 0
Almería
Country [115] 0 0
Spain
State/province [115] 0 0
Granada
Country [116] 0 0
Spain
State/province [116] 0 0
La Coruña
Country [117] 0 0
Spain
State/province [117] 0 0
Partida De Bacarot
Country [118] 0 0
Spain
State/province [118] 0 0
Sevilla
Country [119] 0 0
Spain
State/province [119] 0 0
Valencia
Country [120] 0 0
Spain
State/province [120] 0 0
Valladolid
Country [121] 0 0
Taiwan
State/province [121] 0 0
Taichung City
Country [122] 0 0
Taiwan
State/province [122] 0 0
Tainan city
Country [123] 0 0
Taiwan
State/province [123] 0 0
Taipei
Country [124] 0 0
Taiwan
State/province [124] 0 0
Taoyuan
Country [125] 0 0
Thailand
State/province [125] 0 0
Bangkoknoi, Bangkok
Country [126] 0 0
Thailand
State/province [126] 0 0
Bangkok
Country [127] 0 0
Thailand
State/province [127] 0 0
Chiang Mai
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Belfast
Country [129] 0 0
United Kingdom
State/province [129] 0 0
Bury St Edmunds
Country [130] 0 0
United Kingdom
State/province [130] 0 0
Carmarthen
Country [131] 0 0
United Kingdom
State/province [131] 0 0
Dundee
Country [132] 0 0
United Kingdom
State/province [132] 0 0
Edgbaston, Birmingham
Country [133] 0 0
United Kingdom
State/province [133] 0 0
Fife
Country [134] 0 0
United Kingdom
State/province [134] 0 0
Glasgow
Country [135] 0 0
United Kingdom
State/province [135] 0 0
Gloucester
Country [136] 0 0
United Kingdom
State/province [136] 0 0
Headington
Country [137] 0 0
United Kingdom
State/province [137] 0 0
Lancaster
Country [138] 0 0
United Kingdom
State/province [138] 0 0
Letchworth
Country [139] 0 0
United Kingdom
State/province [139] 0 0
Llantrisant
Country [140] 0 0
United Kingdom
State/province [140] 0 0
London
Country [141] 0 0
United Kingdom
State/province [141] 0 0
St Helens
Country [142] 0 0
United Kingdom
State/province [142] 0 0
Stevenage
Country [143] 0 0
United Kingdom
State/province [143] 0 0
Weston Super Mare
Country [144] 0 0
United Kingdom
State/province [144] 0 0
Wrexham

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novo Nordisk A/S
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This trial is conducted globally. The aim of this trial is to compare the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin degludec (IDeg) and liraglutide (Lira) in subjects with type 2 diabetes. Subjects are to continue their pre-trial treatment with metformin or metformin + pioglitazone throughout the entire trial.
Trial website
https://clinicaltrials.gov/study/NCT01336023
Trial related presentations / 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.
Holst JJ, Buse JB, Rodbard HW, Linjawi S, Woo VC, Boesgaard TW, Kvist K, Gough SC. IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated Using Continuous Glucose Monitoring and a Standardized Meal Test. J Diabetes Sci Technol. 2015 Oct 6;10(2):389-97. doi: 10.1177/1932296815610124.
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.
Gough SC, Bode B, Woo V, Rodbard HW, Linjawi S, Poulsen P, Damgaard LH, Buse JB; NN9068-3697 (DUAL-I) trial investigators. Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes. Lancet Diabetes Endocrinol. 2014 Nov;2(11):885-93. doi: 10.1016/S2213-8587(14)70174-3. Epub 2014 Sep 1.
Gough SC, Bode BW, Woo VC, Rodbard HW, Linjawi S, Zacho M, Reiter PD, Buse JB. One-year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26-week extension to a 26-week main trial. Diabetes Obes Metab. 2015 Oct;17(10):965-73. doi: 10.1111/dom.12498. Epub 2015 Jul 1.
Kapitza C, Bode B, Ingwersen SH, Jacobsen LV, Poulsen P. Preserved pharmacokinetic exposure and distinct glycemic effects of insulin degludec and liraglutide in IDegLira, a fixed-ratio combination therapy. J Clin Pharmacol. 2015 Dec;55(12):1369-77. doi: 10.1002/jcph.549. Epub 2015 Jul 14.
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.
Norwood P, Chen R, Jaeckel E, Lingvay I, Jarlov H, Lehmann L, Heller S. Rates of hypoglycaemia are lower in patients treated with insulin degludec/liraglutide (IDegLira) than with IDeg or insulin glargine, regardless of the hypoglycaemia definition used. Diabetes Obes Metab. 2017 Nov;19(11):1562-1569. doi: 10.1111/dom.12972. Epub 2017 Jul 10.
Public notes

Contacts
Principal investigator
Name 0 0
Global Clinical Registry (GCR, 1452)
Address 0 0
Novo Nordisk A/S
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01336023