Clinical trial NCT02501161: 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
Official title: A Clinical Trial Comparing Long Term Glycaemic Control of Insulin Degludec/Liraglutide (IDegLira) Versus Insulin Glargine Therapy in Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2015-07-17
Enrollment: 1012
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Time From Randomisation to Inadequate Glycaemic Control and Need for Treatment Intensification
timeFrame: Weeks 0-104 + 7 days follow-up-1 + 30 days follow-up-2
Secondary outcomes:
measure: Time From Randomisation to HbA1c >6.5% at 2 Consecutive Visits
timeFrame: Weeks 0-104 + 7 days follow-up-1 + 30 days follow-up-2
measure: Change in HbA1c
timeFrame: Week 0, week 26
measure: Change in Body Weight
timeFrame: Week 0, week 26, week 104
measure: Insulin Dose
timeFrame: Week 26, week 104
measure: Participants Who Achieved (Yes/no): HbA1c <7.0%
timeFrame: Week 26, week 104
measure: Participants Who Achieved (Yes/no): HbA1c <7.0% Without Weight Gain
timeFrame: Week 26, week 104
measure: Participants Who Achieved (Yes/no): HbA1c <7.0% Without Treatment-emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Week 26, week 104
measure: Participants Who Achieved (Yes/no): HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes and Without Weight Gain
timeFrame: Week 26, week 104
measure: Participants Who Achieved (Yes/no): HbA1c ≤6.5%
timeFrame: Week 26, week 104
measure: Participants Who Achieved (Yes/no): HbA1c ≤6.5% Without Weight Gain
timeFrame: Week 26, week 104
measure: Participants Who Achieved (Yes/no): HbA1c ≤6.5% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Week 26, week 104
measure: Participants Who Achieved (Yes/no): HbA1c ≤6.5% Without Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes and Without Weight Gain
timeFrame: Week 26, week 104
measure: Change in FPG
timeFrame: Week 0, week 26, week 104
measure: SMPG-9-point Profile (Individual Points in the Profile)
timeFrame: Week 26, week 104
measure: Change in SMPG-mean 9-point Profile
timeFrame: Week 0, week 26, week 104
measure: Change in SMPG-mean Postprandial Increment Over All Meals
timeFrame: Week 0, week 26, week 104
measure: Change in Blood Pressure (Systolic and Diastolic)
timeFrame: Week 0, week 26, week 104
measure: Change in Fasting C-peptide
timeFrame: Week 0, week 26, week 104
measure: Change in Fasting Human Insulin
timeFrame: Week 0, week 26, week 104
measure: Change in Fasting Total Cholesterol
timeFrame: Week 0, week 26, week 104
measure: Change in Fasting LDL-cholesterol
timeFrame: Week 0, week 26, week 104
measure: Change in Fasting HDL-cholesterol
timeFrame: Week 0, week 26, week 104
measure: Change in Fasting VLDL-cholesterol
timeFrame: Week 0, week 26, week 104
measure: Change in Fasting Triglycerides
timeFrame: Week 0, week 26, week 104
measure: Change in Fasting Free Fatty Acids
timeFrame: Week 0, week 26, week 104
measure: Number of Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During 26 Weeks of Treatment
timeFrame: Weeks 0-26
measure: Number of Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During 104 Weeks of Treatment
timeFrame: Weeks 0-104
measure: Number of Treatment Emergent Hypoglycaemic Episodes During 26 Weeks of Treatment
timeFrame: Weeks 0-26
measure: Number of Treatment Emergent Hypoglycaemic Episodes During 104 Weeks of Treatment
timeFrame: Weeks 0-104
measure: Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During 26 Weeks of Treatment
timeFrame: Weeks 0-26
measure: Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During 104 Weeks of Treatment
timeFrame: Weeks 0-104
measure: Number of TEAEs During 26 Weeks of Treatment
timeFrame: Weeks 0-26
measure: Number of TEAEs During 104 Weeks of Treatment
timeFrame: Week 0 to week 104
measure: Eye Examination Category
timeFrame: Baseline (within 12 weeks prior to week 0), week 104
measure: ECG Evaluation
timeFrame: Baseline (within 2 weeks prior to week 0), week 104
measure: Change in Urine Albumin/Creatinine Ratio
timeFrame: Week 0, week 104
measure: Change in Pulse Rate
timeFrame: Week 0, week 26, week 104
measure: Change in Biochemistry Parameter- Creatinine, Total Bilirubin
timeFrame: Week 0, week 26, week 104
measure: Change in Biochemistry Parameter- Albumin
timeFrame: Week 0, week 26, week 104
measure: Change in Biochemistry Parameters- ALP, ALT, AST, Lipase and Amylase
timeFrame: Week 0, week 26, week 104
measure: Change in Biochemistry Parameter- Sodium, Potassium and Calcium
timeFrame: Week 0, week 26, week 104
measure: Change in Haematological Parameter- Haemoglobin
timeFrame: Week 0, week 26, week 104
measure: Change in Haematological Parameter- Haematocrit
timeFrame: Week 0, week 26, week 104
measure: Change in Haematological Parameter- Erythrocytes
timeFrame: Week 0, week 26, week 104
measure: Change in Haematological Parameter- Thrombocytes and Leukocytes
timeFrame: Week 0, week 26, week 104
measure: Change in Haematological Parameter- Eosinophils
timeFrame: Week 0, week 26, week 104
measure: Change in Haematological Parameter- Neutrophils
timeFrame: Week 0, week 26, week 104
measure: Change in Haematological Parameter- Basophils
timeFrame: Week 0, week 26, week 104
measure: Change in Haematological Parameter- Monocytes
timeFrame: Week 0, week 26, week 104
measure: Change in Haematological Parameter- Lymphocytes
timeFrame: Week 0, week 26, week 104
measure: Change in Calcitonin
timeFrame: Week 0, week 26, week 104
measure: 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)
timeFrame: Week 0, week 26, week 104
measure: Change in TRIM-D
timeFrame: Week 0, week 26, week 104
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Tuscumbia
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Glendale
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Glendale
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Bermuda Dunes
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Fresno
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Lancaster
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Monterey
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Sacramento
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Spring Valley
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Ventura
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Colorado Springs
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Boynton Beach
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Lake Worth
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Blackfoot
country: United States
facility: Novo Nordisk Investigational Site
state: Idaho
city: Avon
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Metairie
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Hyattsville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Rockville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Waltham
country: United States
facility: Novo Nordisk Investigational Site
state: Massachusetts
city: Buckley
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Billings
country: United States
facility: Novo Nordisk Investigational Site
state: Montana
city: Nashua
country: United States
facility: Novo Nordisk Investigational Site
state: New Hampshire
city: Albuquerque
country: United States
facility: Novo Nordisk Investigational Site
state: New Mexico
city: New Windsor
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Mason
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Maumee
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Beaver
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Greer
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Humboldt
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Irving
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Katy
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Midlothian
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Kenosha
country: United States
facility: Novo Nordisk Investigational Site
state: Wisconsin
city: Kenosha
country: United States
facility: Novo Nordisk Investigational Site
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Capital Federal
country: Argentina
facility: Novo Nordisk Investigational Site
city: Mendoza
country: Argentina
facility: Novo Nordisk Investigational Site
city: São Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
state: Sao Paulo
city: Porto Alegre
country: Brazil
facility: Novo Nordisk Investigational Site
city: Plzen
country: Czechia
facility: Novo Nordisk Investigational Site
city: Plzen
country: Czechia
facility: Novo Nordisk Investigational Site
city: Prague 1
country: Czechia
facility: Novo Nordisk Investigational Site
city: Praha 4
country: Czechia
facility: Novo Nordisk Investigational Site
city: Budapest
country: Hungary
facility: Novo Nordisk Investigational Site
city: Budapest
country: Hungary
facility: Novo Nordisk Investigational Site
city: Dunaujvaros
country: Hungary
facility: Novo Nordisk Investigational Site
city: Kaposvár
country: Hungary
facility: Novo Nordisk Investigational Site
city: Pecs
country: Hungary
facility: Novo Nordisk Investigational Site
city: Secunderabad
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Novo Nordisk Investigational Site
state: Andhra Pradesh
city: Rohtak
country: India
facility: Novo Nordisk Investigational Site
state: Haryana
city: Bangalore
country: India
facility: Novo Nordisk Investigational Site
state: Karnataka
city: Mumbai
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Nagpur
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Pune
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Pune
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Delhi
country: India
facility: Novo Nordisk Investigational Site
state: New Delhi
city: Jaipur
country: India
facility: Novo Nordisk Investigational Site
state: Rajasthan
city: Coimbatore
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Kolkata
country: India
facility: Novo Nordisk Investigational Site
state: West Bengal
city: Kolkata
country: India
facility: Novo Nordisk Investigational Site
state: West Bengal
city: Haifa
country: Israel
facility: Novo Nordisk Investigational Site
city: Haifa
country: Israel
facility: Novo Nordisk Investigational Site
city: Nahariya
country: Israel
facility: Novo Nordisk Investigational Site
city: Rishon Le Zion
country: Israel
facility: Novo Nordisk Investigational Site
city: Tel Aviv
country: Israel
facility: Novo Nordisk Investigational Site
city: Tel Hashomer
country: Israel
facility: Novo Nordisk Investigational Site
city: Tel-Aviv
country: Israel
facility: Novo Nordisk Investigational Site
city: Zerifin
country: Israel
facility: Novo Nordisk Investigational Site
city: Bologna
country: Italy
facility: Novo Nordisk Investigational Site
city: Catanzaro
country: Italy
facility: Novo Nordisk Investigational Site
city: Cittadella (PD)
country: Italy
facility: Novo Nordisk Investigational Site
city: Negrar (VR)
country: Italy
facility: Novo Nordisk Investigational Site
city: Palermo
country: Italy
facility: Novo Nordisk Investigational Site
city: Pavia
country: Italy
facility: Novo Nordisk Investigational Site
city: Verona
country: Italy
facility: Novo Nordisk Investigational Site
city: Guadalajara
country: Mexico
facility: Novo Nordisk Investigational Site
state: Jalisco
city: Cuernavaca
country: Mexico
facility: Novo Nordisk Investigational Site
state: Morelos
city: Ciudad Madero
country: Mexico
facility: Novo Nordisk Investigational Site
state: Tamaulipas
city: Durango
country: Mexico
facility: Novo Nordisk Investigational Site
city: Bodø
country: Norway
facility: Novo Nordisk Investigational Site
city: Hamar
country: Norway
facility: Novo Nordisk Investigational Site
city: Hoenefoss
country: Norway
facility: Novo Nordisk Investigational Site
city: Kløfta
country: Norway
facility: Novo Nordisk Investigational Site
city: Lierskogen
country: Norway
facility: Novo Nordisk Investigational Site
city: Oslo
country: Norway
facility: Novo Nordisk Investigational Site
city: Stavanger
country: Norway
facility: Novo Nordisk Investigational Site
city: Tananger
country: Norway
facility: Novo Nordisk Investigational Site
city: Bialystok
country: Poland
facility: Novo Nordisk Investigational Site
city: Gdansk
country: Poland
facility: Novo Nordisk Investigational Site
city: Zabrze
country: Poland
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Novosibirsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Penza
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Stavropol
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Prievidza
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Sabinov
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Trebisov
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Trencin
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Trnava
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Cosmo City
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Johannesburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Pretoria
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Pretoria
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Pretoria
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Umkomaas
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Brits
country: South Africa
facility: Novo Nordisk Investigational Site
state: North West
city: Cape Town
country: South Africa
facility: Novo Nordisk Investigational Site
state: Western Cape
city: Alberton
country: South Africa
facility: Novo Nordisk Investigational Site
city: Ankara
country: Turkey
facility: Novo Nordisk Investigational Site
city: Bursa
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Istanbul
country: Turkey
facility: Novo Nordisk Investigational Site
city: Rize
country: Turkey
facility: Novo Nordisk Investigational Site
city: Samsun
country: Turkey
facility: Novo Nordisk Investigational Site
city: Angus
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Coventry
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Dudley
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Dundee
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Fife
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Hull
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Rotherham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Torquay
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Wolverhampton
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry GCR, 1452
role: STUDY_DIRECTOR
References:
citation: 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.