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

Diabetes Mellitus, Type 2 Clinical Trial

— DUAL™ VIII  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02501161
• Other study ID #: NN9068-4228
• Secondary ID: 2014-005639-15U1
• Status: Completed
• Phase: Phase 3
• Start date: January 31, 2016
• Est. completion date: October 3, 2018

Study information

• Verified date: November 2019
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1012
• Est. completion date: October 3, 2018
• Est. primary completion date: October 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• insulin degludec/liraglutide
Injected subcutaneously (under the skin) once daily for 104 weeks. Dose individually adjusted.
• insulin glargine
Injected subcutaneously (under the skin) once daily for 104 weeks. Dose individually adjusted.

Locations

Country	Name	City	State
Argentina	Novo Nordisk Investigational Site	Buenos Aires
Argentina	Novo Nordisk Investigational Site	Caba
Argentina	Novo Nordisk Investigational Site	Capital Federal
Argentina	Novo Nordisk Investigational Site	Mendoza
Brazil	Novo Nordisk Investigational Site	Porto Alegre
Brazil	Novo Nordisk Investigational Site	São Paulo	Sao Paulo
Czechia	Novo Nordisk Investigational Site	Plzen
Czechia	Novo Nordisk Investigational Site	Plzen
Czechia	Novo Nordisk Investigational Site	Prague 1
Czechia	Novo Nordisk Investigational Site	Praha 4
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Dunaujvaros
Hungary	Novo Nordisk Investigational Site	Kaposvár
Hungary	Novo Nordisk Investigational Site	Pecs
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Coimbatore	Tamil Nadu
India	Novo Nordisk Investigational Site	Delhi	New Delhi
India	Novo Nordisk Investigational Site	Jaipur	Rajasthan
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Kolkata	West Bengal
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	Nagpur	Maharashtra
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Rohtak	Haryana
India	Novo Nordisk Investigational Site	Secunderabad	Andhra Pradesh
India	Novo Nordisk Investigational Site	Visakhapatnam	Andhra Pradesh
Israel	Novo Nordisk Investigational Site	Haifa
Israel	Novo Nordisk Investigational Site	Haifa
Israel	Novo Nordisk Investigational Site	Nahariya
Israel	Novo Nordisk Investigational Site	Rishon Le Zion
Israel	Novo Nordisk Investigational Site	Tel Aviv
Israel	Novo Nordisk Investigational Site	Tel Hashomer
Israel	Novo Nordisk Investigational Site	Tel-Aviv
Israel	Novo Nordisk Investigational Site	Zerifin
Italy	Novo Nordisk Investigational Site	Bologna
Italy	Novo Nordisk Investigational Site	Catanzaro
Italy	Novo Nordisk Investigational Site	Cittadella (PD)
Italy	Novo Nordisk Investigational Site	Negrar (VR)
Italy	Novo Nordisk Investigational Site	Palermo
Italy	Novo Nordisk Investigational Site	Pavia
Italy	Novo Nordisk Investigational Site	Verona
Mexico	Novo Nordisk Investigational Site	Ciudad Madero	Tamaulipas
Mexico	Novo Nordisk Investigational Site	Cuernavaca	Morelos
Mexico	Novo Nordisk Investigational Site	Durango
Mexico	Novo Nordisk Investigational Site	Guadalajara	Jalisco
Norway	Novo Nordisk Investigational Site	Bodø
Norway	Novo Nordisk Investigational Site	Hamar
Norway	Novo Nordisk Investigational Site	Hoenefoss
Norway	Novo Nordisk Investigational Site	Kløfta
Norway	Novo Nordisk Investigational Site	Lierskogen
Norway	Novo Nordisk Investigational Site	Oslo
Norway	Novo Nordisk Investigational Site	Stavanger
Norway	Novo Nordisk Investigational Site	Tananger
Poland	Novo Nordisk Investigational Site	Bialystok
Poland	Novo Nordisk Investigational Site	Gdansk
Poland	Novo Nordisk Investigational Site	Zabrze
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Penza
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	St. Petersburg
Russian Federation	Novo Nordisk Investigational Site	Stavropol
Slovakia	Novo Nordisk Investigational Site	Prievidza
Slovakia	Novo Nordisk Investigational Site	Sabinov
Slovakia	Novo Nordisk Investigational Site	Trebisov
Slovakia	Novo Nordisk Investigational Site	Trencin
Slovakia	Novo Nordisk Investigational Site	Trnava
South Africa	Novo Nordisk Investigational Site	Alberton
South Africa	Novo Nordisk Investigational Site	Brits	North West
South Africa	Novo Nordisk Investigational Site	Cape Town	Western Cape
South Africa	Novo Nordisk Investigational Site	Cosmo City	Gauteng
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
South Africa	Novo Nordisk Investigational Site	Umkomaas	KwaZulu-Natal
Turkey	Novo Nordisk Investigational Site	Ankara
Turkey	Novo Nordisk Investigational Site	Bursa
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Rize
Turkey	Novo Nordisk Investigational Site	Samsun
United Kingdom	Novo Nordisk Investigational Site	Angus
United Kingdom	Novo Nordisk Investigational Site	Coventry
United Kingdom	Novo Nordisk Investigational Site	Dudley
United Kingdom	Novo Nordisk Investigational Site	Dundee
United Kingdom	Novo Nordisk Investigational Site	Fife
United Kingdom	Novo Nordisk Investigational Site	Hull
United Kingdom	Novo Nordisk Investigational Site	Rotherham
United Kingdom	Novo Nordisk Investigational Site	Torquay
United Kingdom	Novo Nordisk Investigational Site	Wolverhampton
United States	Novo Nordisk Investigational Site	Albuquerque	New Mexico
United States	Novo Nordisk Investigational Site	Avon	Indiana
United States	Novo Nordisk Investigational Site	Beaver	Pennsylvania
United States	Novo Nordisk Investigational Site	Bermuda Dunes	California
United States	Novo Nordisk Investigational Site	Billings	Montana
United States	Novo Nordisk Investigational Site	Blackfoot	Idaho
United States	Novo Nordisk Investigational Site	Boynton Beach	Florida
United States	Novo Nordisk Investigational Site	Buckley	Michigan
United States	Novo Nordisk Investigational Site	Colorado Springs	Colorado
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Fresno	California
United States	Novo Nordisk Investigational Site	Glendale	Arizona
United States	Novo Nordisk Investigational Site	Glendale	Arizona
United States	Novo Nordisk Investigational Site	Greer	South Carolina
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Humboldt	Tennessee
United States	Novo Nordisk Investigational Site	Hyattsville	Maryland
United States	Novo Nordisk Investigational Site	Indianapolis	Indiana
United States	Novo Nordisk Investigational Site	Irving	Texas
United States	Novo Nordisk Investigational Site	Katy	Texas
United States	Novo Nordisk Investigational Site	Kenosha	Wisconsin
United States	Novo Nordisk Investigational Site	Kenosha	Wisconsin
United States	Novo Nordisk Investigational Site	Lake Worth	Florida
United States	Novo Nordisk Investigational Site	Lancaster	California
United States	Novo Nordisk Investigational Site	Mason	Ohio
United States	Novo Nordisk Investigational Site	Maumee	Ohio
United States	Novo Nordisk Investigational Site	Metairie	Louisiana
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Midlothian	Virginia
United States	Novo Nordisk Investigational Site	Monterey	California
United States	Novo Nordisk Investigational Site	Muscle Shoals	Alabama
United States	Novo Nordisk Investigational Site	Nashua	New Hampshire
United States	Novo Nordisk Investigational Site	New Windsor	New York
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Rockville	Maryland
United States	Novo Nordisk Investigational Site	Sacramento	California
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	Spring Valley	California
United States	Novo Nordisk Investigational Site	Tuscumbia	Alabama
United States	Novo Nordisk Investigational Site	Ventura	California
United States	Novo Nordisk Investigational Site	Walnut Creek	California
United States	Novo Nordisk Investigational Site	Waltham	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Czechia,  Hungary,  India,  Israel,  Italy,  Mexico,  Norway,  Poland,  Russian Federation,  Slovakia,  South Africa,  Turkey,  United Kingdom, 

References & Publications (1)

Aroda VR, González-Galvez G, Grøn R, Halladin N, Haluzík 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): — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Change in HbA1c	Change in HbA1c from baseline (week 0) to week 26 is presented.	Week 0, week 26
Secondary	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
Secondary	Insulin Dose	Insulin dose after 26 and 104 weeks of treatment is presented.	Week 26, week 104
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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