A 104 Week Clinical Trial Comparing Long Term Glycaemic Control of Insulin Degludec/Liraglutide (IDegLira) Versus Insulin Glargine Therapy in Subjects With Type 2 Diabetes Mellitus (DUAL™ VIII)

A Clinical Trial Comparing Long Term Glycaemic Control of Insulin Degludec/Liraglutide (IDegLira) Versus Insulin Glargine Therapy in Subjects With Type 2 Diabetes Mellitus

This trial is conducted in Africa, Asia, Europe, North America and South America. The purpose is to compare long-term glycaemic control of insulin degludec/liraglutide (IDegLira) versus insulin glargine (IGlar) in insulin naïve subjects with type 2 diabetes mellitus inadequately controlled with oral anti diabetics.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 1012
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425AGC
    • Novo Nordisk Investigational Site
  • Caba, Argentina, C1179AAB
    • Novo Nordisk Investigational Site
  • Capital Federal, Argentina, C1056ABJ
    • Novo Nordisk Investigational Site
  • Mendoza, Argentina, 5500
    • Novo Nordisk Investigational Site
• Brazil
  • Porto Alegre, Brazil, 90035-170
    • Novo Nordisk Investigational Site
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 01228-000
      • Novo Nordisk Investigational Site
• Czechia
  • Plzen, Czechia, 30100
    • Novo Nordisk Investigational Site
  • Plzen, Czechia, 32600
    • Novo Nordisk Investigational Site
  • Prague 1, Czechia, 11694
    • Novo Nordisk Investigational Site
  • Praha 4, Czechia, 140 46
    • Novo Nordisk Investigational Site
• Hungary
  • Budapest, Hungary, H-1134
    • Novo Nordisk Investigational Site
  • Budapest, Hungary, 1106
    • Novo Nordisk Investigational Site
  • Dunaujvaros, Hungary, 2400
    • Novo Nordisk Investigational Site
  • Kaposvár, Hungary, 7400
    • Novo Nordisk Investigational Site
  • Pecs, Hungary, H-7624
    • Novo Nordisk Investigational Site
• India
  • Andhra Pradesh
    • Secunderabad, Andhra Pradesh, India, 500003
      • Novo Nordisk Investigational Site
    • Visakhapatnam, Andhra Pradesh, India, 530002
      • Novo Nordisk Investigational Site
  • Haryana
    • Rohtak, Haryana, India, 124001
      • Novo Nordisk Investigational Site
  • Karnataka
    • Bangalore, Karnataka, India, 560054
      • Novo Nordisk Investigational Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400058
      • Novo Nordisk Investigational Site
    • Nagpur, Maharashtra, India, 440015
      • Novo Nordisk Investigational Site
    • Pune, Maharashtra, India, 411001
      • Novo Nordisk Investigational Site
    • Pune, Maharashtra, India, 411040
      • Novo Nordisk Investigational Site
  • New Delhi
    • Delhi, New Delhi, India, 110002
      • Novo Nordisk Investigational Site
  • Rajasthan
    • Jaipur, Rajasthan, India, 302006
      • Novo Nordisk Investigational Site
  • Tamil Nadu
    • Coimbatore, Tamil Nadu, India, 641018
      • Novo Nordisk Investigational Site
  • West Bengal
    • Kolkata, West Bengal, India, 700020
      • Novo Nordisk Investigational Site
    • Kolkata, West Bengal, India, 700107
      • Novo Nordisk Investigational Site
• Israel
  • Haifa, Israel
    • Novo Nordisk Investigational Site
  • Haifa, Israel, 35152
    • Novo Nordisk Investigational Site
  • Nahariya, Israel, 22100
    • Novo Nordisk Investigational Site
  • Rishon Le Zion, Israel, 75650
    • Novo Nordisk Investigational Site
  • Tel Aviv, Israel, 6789714
    • Novo Nordisk Investigational Site
  • Tel Hashomer, Israel, 52621
    • Novo Nordisk Investigational Site
  • Tel-Aviv, Israel, 62038
    • Novo Nordisk Investigational Site
  • Zerifin, Israel, 70300
    • Novo Nordisk Investigational Site
• Italy
  • Bologna, Italy, 40138
    • Novo Nordisk Investigational Site
  • Catanzaro, Italy, 88100
    • Novo Nordisk Investigational Site
  • Cittadella (PD), Italy, 35013
    • Novo Nordisk Investigational Site
  • Negrar (VR), Italy, 37024
    • Novo Nordisk Investigational Site
  • Palermo, Italy, 90129
    • Novo Nordisk Investigational Site
  • Pavia, Italy, 27100
    • Novo Nordisk Investigational Site
  • Verona, Italy, 37126
    • Novo Nordisk Investigational Site
• Mexico
  • Durango, Mexico, 34000
    • Novo Nordisk Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44600
      • Novo Nordisk Investigational Site
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62250
      • Novo Nordisk Investigational Site
  • Tamaulipas
    • Ciudad Madero, Tamaulipas, Mexico, 89440
      • Novo Nordisk Investigational Site
• Norway
  • Bodø, Norway, 8005
    • Novo Nordisk Investigational Site
  • Hamar, Norway, 2317
    • Novo Nordisk Investigational Site
  • Hoenefoss, Norway, 3515
    • Novo Nordisk Investigational Site
  • Kløfta, Norway, 2040
    • Novo Nordisk Investigational Site
  • Lierskogen, Norway, 3420
    • Novo Nordisk Investigational Site
  • Oslo, Norway, 0424
    • Novo Nordisk Investigational Site
  • Stavanger, Norway, 4005
    • Novo Nordisk Investigational Site
  • Tananger, Norway, 4056
    • Novo Nordisk Investigational Site
• Poland
  • Bialystok, Poland, 15-276
    • Novo Nordisk Investigational Site
  • Gdansk, Poland, 80-858
    • Novo Nordisk Investigational Site
  • Zabrze, Poland, 41-800
    • Novo Nordisk Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 119435
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 119121
    • Novo Nordisk Investigational Site
  • Novosibirsk, Russian Federation, 630117
    • Novo Nordisk Investigational Site
  • Penza, Russian Federation, 440026
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 194358
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 195213
    • Novo Nordisk Investigational Site
  • St. Petersburg, Russian Federation, 194354
    • Novo Nordisk Investigational Site
  • Stavropol, Russian Federation, 355035
    • Novo Nordisk Investigational Site
• Slovakia
  • Prievidza, Slovakia, 97101
    • Novo Nordisk Investigational Site
  • Sabinov, Slovakia, 08301
    • Novo Nordisk Investigational Site
  • Trebisov, Slovakia, 07501
    • Novo Nordisk Investigational Site
  • Trencin, Slovakia, 911 01
    • Novo Nordisk Investigational Site
  • Trnava, Slovakia, 91701
    • Novo Nordisk Investigational Site
• South Africa
  • Alberton, South Africa, 1449
    • Novo Nordisk Investigational Site
  • Gauteng
    • Cosmo City, Gauteng, South Africa, 2188
      • Novo Nordisk Investigational Site
    • Johannesburg, Gauteng, South Africa, 1818
      • Novo Nordisk Investigational Site
    • Pretoria, Gauteng, South Africa, 0083
      • Novo Nordisk Investigational Site
    • Pretoria, Gauteng, South Africa, 0002
      • Novo Nordisk Investigational Site
    • Pretoria, Gauteng, South Africa, 0183
      • Novo Nordisk Investigational Site
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4001
      • Novo Nordisk Investigational Site
    • Durban, KwaZulu-Natal, South Africa, 4170
      • Novo Nordisk Investigational Site
    • Umkomaas, KwaZulu-Natal, South Africa, 4170
      • Novo Nordisk Investigational Site
  • North West
    • Brits, North West, South Africa, 0250
      • Novo Nordisk Investigational Site
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7700
      • Novo Nordisk Investigational Site
• Turkey
  • Ankara, Turkey, 06100
    • Novo Nordisk Investigational Site
  • Bursa, Turkey
    • Novo Nordisk Investigational Site
  • Istanbul, Turkey, 34096
    • Novo Nordisk Investigational Site
  • Istanbul, Turkey, 34390
    • Novo Nordisk Investigational Site
  • Istanbul, Turkey, 34718
    • Novo Nordisk Investigational Site
  • Istanbul, Turkey, 34899
    • Novo Nordisk Investigational Site
  • Rize, Turkey, 53020
    • Novo Nordisk Investigational Site
  • Samsun, Turkey, 55139
    • Novo Nordisk Investigational Site
• United Kingdom
  • Angus, United Kingdom, DD8 2AS
    • Novo Nordisk Investigational Site
  • Coventry, United Kingdom, CV2 2DX
    • Novo Nordisk Investigational Site
  • Dudley, United Kingdom, DY1 2HQ
    • Novo Nordisk Investigational Site
  • Dundee, United Kingdom, DD4 6QY
    • Novo Nordisk Investigational Site
  • Fife, United Kingdom, KY14 6AW
    • Novo Nordisk Investigational Site
  • Hull, United Kingdom, HU3 2RW
    • Novo Nordisk Investigational Site
  • Rotherham, United Kingdom, S60 2UD
    • Novo Nordisk Investigational Site
  • Torquay, United Kingdom, TQ2 7AA
    • Novo Nordisk Investigational Site
  • Wolverhampton, United Kingdom, WV10 0QP
    • Novo Nordisk Investigational Site
• United States
  • Alabama
    • Muscle Shoals, Alabama, United States, 35662
      • Novo Nordisk Investigational Site
    • Tuscumbia, Alabama, United States, 35674
      • Novo Nordisk Investigational Site
  • Arizona
    • Glendale, Arizona, United States, 85306-4652
      • Novo Nordisk Investigational Site
    • Glendale, Arizona, United States, 85308
      • Novo Nordisk Investigational Site
    • Phoenix, Arizona, United States, 85050
      • Novo Nordisk Investigational Site
    • Phoenix, Arizona, United States, 85018
      • Novo Nordisk Investigational Site
    • Phoenix, Arizona, United States, 85020
      • Novo Nordisk Investigational Site
  • California
    • Bermuda Dunes, California, United States, 92203
      • Novo Nordisk Investigational Site
    • Fresno, California, United States, 93720
      • Novo Nordisk Investigational Site
    • Lancaster, California, United States, 93534
      • Novo Nordisk Investigational Site
    • Monterey, California, United States, 93940
      • Novo Nordisk Investigational Site
    • Sacramento, California, United States, 95821
      • Novo Nordisk Investigational Site
    • Spring Valley, California, United States, 91978
      • Novo Nordisk Investigational Site
    • Ventura, California, United States, 93003
      • Novo Nordisk Investigational Site
    • Walnut Creek, California, United States, 94598
      • Novo Nordisk Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • Novo Nordisk Investigational Site
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Novo Nordisk Investigational Site
    • Lake Worth, Florida, United States, 33461
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33135
      • Novo Nordisk Investigational Site
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Novo Nordisk Investigational Site
  • Indiana
    • Avon, Indiana, United States, 46123
      • Novo Nordisk Investigational Site
    • Indianapolis, Indiana, United States, 46254
      • Novo Nordisk Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70002
      • Novo Nordisk Investigational Site
  • Maryland
    • Hyattsville, Maryland, United States, 20782
      • Novo Nordisk Investigational Site
    • Rockville, Maryland, United States, 20852
      • Novo Nordisk Investigational Site
  • Massachusetts
    • Waltham, Massachusetts, United States, 02453
      • Novo Nordisk Investigational Site
  • Michigan
    • Buckley, Michigan, United States, 49620
      • Novo Nordisk Investigational Site
  • Montana
    • Billings, Montana, United States, 59101
      • Novo Nordisk Investigational Site
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Novo Nordisk Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Novo Nordisk Investigational Site
  • New York
    • New Windsor, New York, United States, 12553
      • Novo Nordisk Investigational Site
  • Ohio
    • Mason, Ohio, United States, 45040-6815
      • Novo Nordisk Investigational Site
    • Maumee, Ohio, United States, 43537
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • Novo Nordisk Investigational Site
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Novo Nordisk Investigational Site
  • Tennessee
    • Humboldt, Tennessee, United States, 38343
      • Novo Nordisk Investigational Site
  • Texas
    • Dallas, Texas, United States, 75251
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77040
      • Novo Nordisk Investigational Site
    • Irving, Texas, United States, 75061-2210
      • Novo Nordisk Investigational Site
    • Katy, Texas, United States, 77450
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78215
      • Novo Nordisk Investigational Site
  • Virginia
    • Midlothian, Virginia, United States, 23114
      • Novo Nordisk Investigational Site
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53142
      • Novo Nordisk Investigational Site
    • Kenosha, Wisconsin, United States, 53144
      • 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:

• Male or female, age greater than or equal to 18 years at the time of signing informed consent
• Subjects diagnosed with type 2 diabetes mellitus
• HbA1c 7.0-11.0% (both inclusive) (53-97 mmol/mol) by central laboratory analysis
• Body mass index greater than or equal to 20 kg/m^2
• Insulin naïve subjects; however short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes
• Stable daily dose(s) including any of the following antidiabetic drug(s)/regimens within 90 days prior to the day of screening: a) Biguanides (metformin greater than or equal to 1500 mg or maximum tolerated dose documented in the subject medical record), b) Other OAD(s) allowed: sulphonylurea, glinides, pioglitazone, and DPP4-inhibitors (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated dose as documented in subjects medical record)

Exclusion Criteria:

• Screening calcitonin greater than or equal to 50 ng/L
• Renal impairment estimated Glomerular Filtration Rate (eGFR) less than 60 ml/min/1.73 m2 as per CKD-EPI value to be defined as listed in the classification CKD-EPI using IDMS for serum creatinine measurement on the day of screening
• Impaired liver function, defined as ALAT or ASAT greater than or equal to 2.5 times upper limit of normal
• Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma
• History of pancreatitis (acute or chronic)
• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening
• Anticipated initiation or change in concomitant medications for more than 14 consecutive days or on a frequent basis known to affect weight or glucose metabolism (e.g. orlistat, thyroid hormones, corticosteroids)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin degludec/liraglutide QD + OAD(s)	Drug: insulin degludec/liraglutide; Injected subcutaneously (under the skin) once daily for 104 weeks. Dose individually adjusted.
Active Comparator: insulin glargine QD + OAD(s)	Drug: insulin glargine; Injected subcutaneously (under the skin) once daily for 104 weeks. Dose individually adjusted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Randomisation to Inadequate Glycaemic Control and Need for Treatment Intensification	Inadequate glycaemic control and need for treatment intensification was defined as a glycosylated haemoglobin (HbA1c) of 7.0% or greater at 2 consecutive visits from week 26, including week 26 if HbA1c was greater than or equal to 7% at week 12. Time from randomisation to inadequate glycaemic control and need for treatment intensification was analysed using a stratified log-rank test where treatment, baseline HbA1c group and previous OAD treatment were included as strata in the model. The variable "baseline HbA1c group" was a dichotomised baseline HbA1c variable with 2 categories: HbA1c < 8.5% or HbA1c ≥ 8.5% and the variable "previous OAD treatment" was a categorical variable with 2 categories: SU ± OAD(s) (SU users) or OAD(s) (Non-SU users). 25%, median (50%) and 75% percentiles for the cumulative distribution function were obtained from the Kaplan-Meier survival function.	Weeks 0-104 + 7 days follow-up-1 + 30 days follow-up-2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Randomisation to HbA1c >6.5% at 2 Consecutive Visits	Time to HbA1c > 6.5% at 2 consecutive visits is defined as time from randomization to HbA1c > 6.5% at 2 consecutive planned scheduled visits from week 26 (including week 26 if HbA1c was > 6.5% at week 12). Time from randomisation to HbA1c >6.5% at 2 consecutive visits was analysed using a stratified log-rank test where treatment, baseline HbA1c group and previous OAD treatment were included as strata in the model. The variable "baseline HbA1c group" was a dichotomised baseline HbA1c variable with 2 categories: HbA1c < 8.5% or HbA1c ≥ 8.5% and the variable "previous OAD treatment" was a categorical variable with 2 categories: SU ± OAD(s) (SU users) or OAD(s) (Non-SU users). 25%, median (50%) and 75% percentiles for the cumulative distribution function were obtained from the Kaplan-Meier survival function.	Weeks 0-104 + 7 days follow-up-1 + 30 days follow-up-2
Change in HbA1c	Change in HbA1c from baseline (week 0) to week 26 is presented.	Week 0, week 26
Change in Body Weight	Change in body weight from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Insulin Dose	Insulin dose after 26 and 104 weeks of treatment is presented.	Week 26, week 104
Participants Who Achieved (Yes/no): HbA1c <7.0%	Percentage of participants who achieved (yes/no) HbA1c <7.0% at week 26 and week 104 is presented.	Week 26, week 104
Participants Who Achieved (Yes/no): HbA1c <7.0% Without Weight Gain	Percentage of participants who achieved (yes/no) HbA1c <7.0% without weight gain at week 26 and week 104 is presented.	Week 26, week 104
Participants Who Achieved (Yes/no): HbA1c <7.0% Without Treatment-emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes	Severe or BG confirmed symptomatic hypoglycaemia was defined as an episode that was severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Percentage of participants who achieved (yes/no) HbA1c <7.0% without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes at week 26 and week 104 is presented.	Week 26, week 104
Participants Who Achieved (Yes/no): HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes and Without Weight Gain	Severe or BG confirmed symptomatic hypoglycaemia was defined as an episode that was severe according to the ADA classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Percentage of participants who achieved (yes/no) HbA1c <7.0% without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes and without weight gain at week 26 and week 104 is presented.	Week 26, week 104
Participants Who Achieved (Yes/no): HbA1c ≤6.5%	Percentage of participants who achieved (yes/no) HbA1c ≤6.5% at week 26 and week 104 is presented.	Week 26, week 104
Participants Who Achieved (Yes/no): HbA1c ≤6.5% Without Weight Gain	Percentage of participants who achieved (yes/no) HbA1c ≤6.5% without weight gain at week 26 and week 104 is presented.	Week 26, week 104
Participants Who Achieved (Yes/no): HbA1c ≤6.5% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes	Severe or BG confirmed symptomatic hypoglycaemia is defined as an episode that is severe according to the ADA classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Percentage of participants who achieved (yes/no) HbA1c ≤6.5% without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes at week 26 and week 104 is presented.	Week 26, week 104
Participants Who Achieved (Yes/no): HbA1c ≤6.5% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes and Without Weight Gain	Severe or BG confirmed symptomatic hypoglycaemia is defined as an episode that is severe according to the ADA classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Percentage of participants who achieved (yes/no) HbA1c ≤6.5% without treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes and without weight gain at week 26 and week 104 is presented.	Week 26, week 104
Change in FPG	Change in fasting plasma glucose (FPG) from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
SMPG-9-point Profile (Individual Points in the Profile)	Participants measured plasma glucose values using the blood glucose meter at 9 time points: before breakfast, 90 min after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 min after start of dinner, bedtime, at 4:00 am and before breakfast the following day. Self-measured plasma glucose (SMPG)-9-point profile (individual points in the profile) at week 26 and week 104 is presented.	Week 26, week 104
Change in SMPG-mean 9-point Profile	Participants measured plasma glucose values using the blood glucose meter at 9 time points: before breakfast, 90 min after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 min after start of dinner, bedtime, at 4:00 am and before breakfast the following day. Change in SMPG-mean 9-point profile from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in SMPG-mean Postprandial Increment Over All Meals	Participants measured plasma glucose values using the blood glucose meter at 9 time points: before breakfast, 90 min after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 min after start of dinner, bedtime, at 4:00 am and before breakfast the following day. Change in SMPG-mean postprandial increment over all meals from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Blood Pressure (Systolic and Diastolic)	Change in blood pressure (systolic and diastolic) from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Fasting C-peptide	Change in fasting C-peptide (measured in nanomoles per liter [nmol/L]) from baseline (week 0) to week 26 and week 104 is presented as ratio to baseline.	Week 0, week 26, week 104
Change in Fasting Human Insulin	Change in fasting human insulin (measured in picomoles per liter [pmol/L]) from baseline (week 0) to week 26 and week 104 is presented as ratio to baseline.	Week 0, week 26, week 104
Change in Fasting Total Cholesterol	Change in fasting total cholesterol (measured in mmol/L) from baseline (week 0) to week 26 and week 104 is presented as ratio to baseline.	Week 0, week 26, week 104
Change in Fasting LDL-cholesterol	Change in fasting low density lipoprotein (LDL)-cholesterol (measured in mmol/L) from baseline (week 0) to week 26 and week 104 is presented as ratio to baseline.	Week 0, week 26, week 104
Change in Fasting HDL-cholesterol	Change in fasting high density lipoprotein (HDL)- cholesterol (measured in mmol/L) from baseline (week 0) to week 26 and week 104 is presented as ratio to baseline.	Week 0, week 26, week 104
Change in Fasting VLDL-cholesterol	Change in fasting very low density lipoprotein (VLDL)-cholesterol (measured in mmol/L) from baseline (week 0) to week 26 and week 104 is presented as ratio to baseline.	Week 0, week 26, week 104
Change in Fasting Triglycerides	Change in fasting triglycerides (measured as mmol/L) from baseline (week 0) to week 26 and week 104 is presented as ratio to baseline.	Week 0, week 26, week 104
Change in Fasting Free Fatty Acids	Change in fasting free fatty acids (measured as mmol/L) from baseline (week 0) to week 26 and week 104 is presented as ratio to baseline.	Week 0, week 26, week 104
Number of Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During 26 Weeks of Treatment	Severe or BG confirmed symptomatic hypoglycaemia is defined as an episode that is severe according to the ADA classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during 26 weeks of treatment is presented.	Weeks 0-26
Number of Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During 104 Weeks of Treatment	Severe or BG confirmed symptomatic hypoglycaemia is defined as an episode that is severe according to the ADA classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during 104 weeks of treatment is presented.	Weeks 0-104
Number of Treatment Emergent Hypoglycaemic Episodes During 26 Weeks of Treatment	Hypoglycaemic episodes (SMPG value ≤3.9 mmol/L (70 mg/dL)) were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of treatment-emergent hypoglycaemic episodes according to ADA during 26 weeks of treatment is presented.	Weeks 0-26
Number of Treatment Emergent Hypoglycaemic Episodes During 104 Weeks of Treatment	Hypoglycaemic episodes (SMPG value ≤3.9 mmol/L (70 mg/dL)) were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of treatment emergent hypoglycaemic episodes according to ADA during 104 weeks of treatment is presented.	Weeks 0-104
Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During 26 Weeks of Treatment	Severe or BG confirmed symptomatic hypoglycaemia is defined as an episode that is severe according to the ADA classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Nocturnal hypoglycaemic episodes were episodes occurring between 00:01 and 05.59 both inclusive. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of treatment-emergent nocturnal severe or BG confirmed symptomatic hypoglycaemic episodes during 26 weeks of treatment is presented.	Weeks 0-26
Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During 104 Weeks of Treatment	Severe or BG confirmed symptomatic hypoglycaemia is defined as an episode that is severe according to the ADA classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Nocturnal hypoglycaemic episodes were episodes occurring between 00:01 and 05.59 both inclusive. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of treatment-emergent nocturnal severe or BG confirmed symptomatic hypoglycaemic episodes during 104 weeks of treatment is presented.	Weeks 0-104
Number of TEAEs During 26 Weeks of Treatment	An adverse event is any untoward medical occurrence in a participant administered a product, and which does not necessarily have a causal relationship with this treatment. A treatment emergent adverse event (TEAE) was defined as an adverse event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product. If the event had onset date before the first day of exposure on trial product and increased in severity during the treatment period and until 7 days after the last drug date, then this event was also considered as a TEAE. Number of TEAEs during 26 weeks of treatment is presented.	Weeks 0-26
Number of TEAEs During 104 Weeks of Treatment	An adverse event is any untoward medical occurrence in a participant administered a product, and which does not necessarily have a causal relationship with this treatment. A TEAE was defined as an adverse event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product. If the event had onset date before the first day of exposure on trial product and increased in severity during the treatment period and until 7 days after the last drug date, then this event was also considered as a TEAE. Number of TEAEs during 104 weeks of treatment is presented.	Week 0 to week 104
Eye Examination Category	Fundus photography or a dilated fundoscopy was performed at baseline (within 12 weeks prior to week 0) and week 104. The investigator interpreted each eye's (left and right) results and categorised them as: normal, abnormal not clinically significant (NCS) or abnormal clinically significant (CS). Number of participants in each category at baseline and week 104 were presented.	Baseline (within 12 weeks prior to week 0), week 104
ECG Evaluation	The electrocardiogram (ECG) was assessed at baseline (within 2 weeks prior to week 0) and week 104. The investigator interpreted the results and categorised them as: normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline and week 104 are presented.	Baseline (within 2 weeks prior to week 0), week 104
Change in Urine Albumin/Creatinine Ratio	Change in urine albumin/creatinine ratio from baseline (week 0) to week 104 is presented.	Week 0, week 104
Change in Pulse Rate	Change in pulse rate from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Biochemistry Parameter- Creatinine, Total Bilirubin	Change in biochemistry parameter- creatinine, total bilirubin from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Biochemistry Parameter- Albumin	Change in biochemistry parameter- albumin from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Biochemistry Parameters- ALP, ALT, AST, Lipase and Amylase	Change in biochemistry parameters- alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipase and amylase from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Biochemistry Parameter- Sodium, Potassium and Calcium	Change in sodium, potassium and calcium from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Haematological Parameter- Haemoglobin	Change in haemoglobin from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Haematological Parameter- Haematocrit	Change in haematocrit from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Haematological Parameter- Erythrocytes	Change in erythrocytes from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Haematological Parameter- Thrombocytes and Leukocytes	Change in thrombocytes and leukocytes from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Haematological Parameter- Eosinophils	Change in eosinophils from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Haematological Parameter- Neutrophils	Change in neutrophils from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Haematological Parameter- Basophils	Change in basophils from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Haematological Parameter- Monocytes	Change in monocytes from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Haematological Parameter- Lymphocytes	Change in lymphocytes from baseline (week 0) to week 26 and week 104 is presented.	Week 0, week 26, week 104
Change in Calcitonin	The number of participants who reported low, normal and high levels of calcitonin in relation to reference ranges at baseline (week 0), week 26 and week 104 are presented.	Week 0, week 26, week 104
Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS)	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in the sub-domain scores and component summary (PCS and MCS) scores are presented. A positive change score indicates an improvement since baseline.	Week 0, week 26, week 104
Change in TRIM-D	Treatment related impact measures-diabetes (TRIM-D) was developed according to the FDA guidance from 2009 on development of new PRO measures. The questionnaire consists of 5 sub-domains, which are scored according to a 1-5 point scale with a higher score indicating a better health state (less negative impact). Sub-domain scores are calculated by summing across items in the same sub-domain, and the total score is calculated by summing scores from all the sub-domains. The highest possible summed score within a sub-domain ranges from 20 (compliance sub-domain) to 40 (psychological health sub-domain) points and the highest possible total score is 140 points. Change in TRIM-D total score from baseline (week 0) to week 26 and week 104 is presented. A positive change score indicates an improvement since baseline.	Week 0, week 26, week 104

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Global Clinical Registry GCR, 1452, Novo Nordisk A/S

Publications and helpful links

General Publications

• Aroda VR, Gonzalez-Galvez G, Gron R, Halladin N, Haluzik M, Jermendy G, Kok A, Orsy P, Sabbah M, Sesti G, Silver R. Durability of insulin degludec plus liraglutide versus insulin glargine U100 as initial injectable therapy in type 2 diabetes (DUAL VIII): a multicentre, open-label, phase 3b, randomised controlled trial. Lancet Diabetes Endocrinol. 2019 Aug;7(8):596-605. doi: 10.1016/S2213-8587(19)30184-6. Epub 2019 Jun 9.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2016
• Primary Completion (Actual): October 3, 2018
• Study Completion (Actual): October 3, 2018

Study Registration Dates

• First Submitted: July 15, 2015
• First Submitted That Met QC Criteria: July 15, 2015
• First Posted (Estimate): July 17, 2015

Study Record Updates

• Last Update Posted (Actual): November 27, 2019
• Last Update Submitted That Met QC Criteria: November 8, 2019
• Last Verified: November 1, 2019

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; Liraglutide; Insulin Glargine; Xultophy
• Other Study ID Numbers: NN9068-4228; 2014-005639-15 (EudraCT Number); U1111-1165-3914 (Other Identifier: WHO)