A Clinical Proof-of-principle Trial in Adult Subjects With Newly Diagnosed Type 1 Diabetes Mellitus Investigating the Effect of NNC0114-0006 and Liraglutide on Preservation of Beta-cell Function

Phase 2

Completed

Conditions: Diabetes
Diabetes Mellitus, Type 1

Interventions: Drug: NNC0114-0006
Drug: placebo
Drug: liraglutide

Registration Number: NCT02443155

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted globally. The aim of this trial is to assess the clinical proof-of-principle of NNC0114-0006 and liraglutide on preservation of beta-cell function in adult subjects with newly diagnosed type 1 diabetes mellitus.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 308

Inclusion Criteria

Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
T1DM (type 1 diabetes mellitus) (as diagnosed clinically) for not more than 20 weeks prior to screening - Male or female, aged 18-45 (both inclusive) at the time of signing the informed consent form
Non-fasting peak C-peptide higher or equal to 0.2 nmol/l at visit 2
BMI (body mass index) higher or equal to 18.5 kg/m^2
Presence of one or more islet specific auto antibodies (glutamic acid decarboxylase (GAD), islet antigen-2 (IA2) or zinc-transporter 8 (ZnT8)) at screening
Insulin dependence unless in temporary spontaneous remission (honeymoon period)

Exclusion Criteria

Daily insulin usage above 1 U/kg per day at screening or use of continuous subcutaneous insulin infusion (CSII)
History of recurrent (e.g. several times a year) of severe (e.g. pneumonia) or chronic infections or conditions predisposing to chronic infections (e.g., bronchiectasis and chronic osteomyelitis)
History of severe systemic fungal infection within the past 12 months prior to screening unless treated and resolved with appropriate documented therapy
Vaccination within 4 weeks before randomisation, Visit 3 (V3)
Receipt of any other concomitant medications or herbal products that can influence the immune system within 90 days prior to screening (V1)
History of pancreatitis (acute or chronic)
Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN2) or Medullary Thyroid Carcinoma (MTC)
Any past or current diagnosis of malignant neoplasms
Known impairment of the immune system, except for T1DM, coeliac disease, alopecia, autoimmune antibodies not considered clinical important (e.g. thyroid antibodies without any clinically important thyroid disease), and vitiligo

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NNC0114-0006 + Placebo	placebo	-
Liraglutide + Placebo	placebo	-
Placebo	placebo	-
NNC0114-0006 + Liraglutide	NNC0114-0006	-
NNC0114-0006 + Liraglutide	liraglutide	-
Liraglutide + Placebo	liraglutide	-
NNC0114-0006 + Placebo	NNC0114-0006	-

Primary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve (AUC) 0-4h of Mixed Meal Tolerance Test (MMTT) Stimulated C-peptide at Week 54 Relative to Baseline	0 - 4 hours post-dose on week 0 and week 54	Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a mixed meal tolerance test (MMTT) stimulated C-peptide at week 54 is presented as ratio to baseline. AUC of C-peptide was measured as Nano moles\hour per liter (nmol\h/L).

Secondary Outcome Measures

Name	Time	Method
Estimated Glomerular Filtration Rate (eGFR)- Ratio to Baseline	(Week 0, week 54) and (week 0, week 80)	The eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Change in eGFR (measured in milliliters per minute per 1.73 square meters) from baseline (week 0) at week 54 and week 80 is presented as ratio to baseline.
Change in Haematology: Mean Corpuscular Hemoglobin	(Week 0, week 54) and (week 0, week 80)	Change in mean Corpuscular hemoglobin (measured in femtomole 'fmol') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
AUC0-4h of Glucose at Week 54 Relative to Baseline	0 - 4 hours post-dose on week 0 and week 54	Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a MMTT stimulated glucose at week 54 is presented as ratio to baseline. AUC of glucose was measured as Milli moles\hour per liter (mmol\h/L).
Cmax of Glucose at Week 54 Relative to Baseline	0-4 hours post-dose on week 0 and week 54	Maximum observed concentration (Cmax) of a MMTT stimulated glucose at week 54 is presented as ratio to baseline. Cmax of C-peptide was measured as 'mmol/L'.
Number of Participants Experiencing Treatment Emergent Injection/Infusion Site Reactions Caused by NNC0114-0006/Liraglutide/Placebo Injection/Infusion	Week 0-54	Injection/infusion site reactions episodes were defined as treatment-emergent if the onset occurred on or after the first day of trial product administration. Number of participants experiencing treatment emergent episodes of injection/infusion site reactions episodes from first dose of trial product to week 54 (treatment period) is presented.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association (ADA)	Weeks 0-54; Weeks 54-80	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 1 day after the date of last contact. Number of treatment-emergent hypoglycaemic episodes according to American Diabetes Association (ADA) classification from first dose of trial product to week 54 and from week 54 to week 80 are presented. Results presented hypoglycaemia episodes were recorded as per ADA definition: Severe hypoglycaemia, Documented symptomatic hypoglycaemia, Asymptomatic hypoglycaemia, Probable symptomatic hypoglycaemia and Pseudo-hypoglycaemia.
Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk Definitions	Weeks 0-54; Weeks 54-80	Hypoglycaemia episodes were recorded as per Novo Nordisk definition: Symptomatic BG-confirmed: An episode that is blood glucose (BG) confirmed by plasma glucose (PG) value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. Asymptomatic BG-confirmed: An episode that is BG-confirmed by PG value \<3.1 mmol/L without symptoms consistent with hypoglycaemia. Severe or BG-confirmed symptomatic: An episode that is severe according to the ISPAD classification or BG-confirmed by a PG value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. BG-confirmed: An episode that is BG-confirmed by a PG value \<3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Severe or BG-confirmed: An episode that is severe according to the International Society for Pediatric and Adolescent Diabetes (ISPAD) classification or BG-confirmed by a PG value \<3.1 mmol/L with or without symptoms consistent with hypoglycaemia.
Change in Haematology: Mean Corpuscular Volume	(Week 0, week 54) and (week 0, week 80)	Change in Mean Corpuscular volume (measured in femtoliter 'fL') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Haematology: Thrombocytes	(Week 0, week 54) and (week 0, week 80)	Change in thrombocytes (measured in 10\^9 cells per liter) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Haematology: Eosinophil	(Week 0, week 54) and (week 0, week 80)	Change in eosinophil (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Haematology: Neutrophils	(Week 0, week 54) and (week 0, week 80)	Change in neutrophils (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Cmax of C-peptide at Week 54 Relative to Baseline	0-4 hours post-dose on week 0 and week 54	Maximum observed concentration (Cmax) of a MMTT stimulated C-peptide at week 54 is presented as ratio to baseline. Cmax of C-peptide was measured as nanomoles per liter (nmol/L).
Change in Haematology: Erythrocytes	(Week 0, week 54) and (week 0, week 80)	Change in erythrocytes (measured in 10\^12 cells per liter) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
AUC0-2h of C-peptide at Week 54 Relative to Baseline	0-2 hours post-dose on week 0 and week 54	Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated C-peptide at week 54 is presented as ratio to baseline. AUC of C-peptide was measured as 'nmol\*h/L'.
Number of Treatment Emergent Adverse Events	Week 0-54; Week 54-80	An adverse event was any untoward medical occurrence in a participants administered a product, and which did not necessarily have a causal relationship with this treatment. An adverse event was defined as treatment emergent if the onset of the adverse event occurs on or after the first day of trial product administration. Number of treatment emergent adverse events from first dose of trial product to week 54 and week 80 are presented. Results are based on the on-treatment and on-observation period. On-treatment period: From the day of first trial product administration to the day of the visit at week 54. On-observation: From the day after the visit at week 54 to the day of the last visit.
Number of Treatment Emergent Hyperglycaemic Episodes	Week 0-54; Week 54-80	Hyperglycaemic episodes were defined as treatment-emergent if the onset occurred on or after the first day of trial product administration. Number of treatment emergent episodes of hyperglycaemic episodes from first dose of trial product to week 54 and from week 54 to week 80 are presented. Results are based on the on-treatment and on-observation period. On-treatment period: From the day of first trial product administration to the day of the visit at week 54. On-observation: From the day after the visit at week 54 to the day of the last visit.
Number of Treatment Emergent Episodes of Diabetic Ketoacidosis	Weeks 0-54; Weeks 54-80	Diabetic ketoacidosis episodes were defined as treatment-emergent if the onset occurred on or after the first day of trial product administration. Number of treatment emergent episodes of hyperglycaemic episodes from first dose of trial product to week 54 and from week 54 to week 80 are presented. Results are based on the on-treatment and on-observation period. On-treatment period: From the day of first trial product administration to the day of the visit at week 54. On-observation: From the day after the visit at week 54 to the day of the last visit.
Change in Body Weight (kg)	(Week 0, week 54) and (week 0, week 80)	Change in body weight is measured at week 54 and week 80 respective to baseline. Body weight was measured in unit 'Kg'.
Diabetes Retinopathy	Baseline, week 54 and week 80	Number of participants evaluated for diabetic retinopathy at baseline (Day -28 to -14), week 54 and week 80 are presented as 'yes', 'no' or 'unknown'.
Change in Haematology: Haematocrit	(Week 0, week 54) and (week 0, week 80)	Change in haematocrit (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Haematology: Haemoglobin	(Week 0, week 54) and (week 0, week 80)	Change in haemoglobin (measured in millimoles per liter 'mmol/L') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Haematology: Leukocytes	(Week 0, week 54) and (week 0, week 80)	Change in leukocytes (measured in 10\^9 cells/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
AUC0-2h of Glucose at Week 54 Relative to Baseline	0-2 hours post-dose on week 0 and week 54	Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated glucose at week 54 is presented as ratio to baseline. AUC of glucose is measured as 'mmol\*h/L'.
Change in Haematology: Mean Corpuscular Hemoglobin Concentration	(Week 0, week 54) and (week 0, week 80)	Change in mean corpuscular hemoglobin concentration (MCHC) (measured in gram per liter 'g/L') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Haematology: Basophils	(Week 0, week 54) and (week 0, week 80)	Change in basophils (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Haematology: Lymphocytes	(Week 0, week 54) and (week 0, week 80)	Change in lymphocytes (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Haematology: Monocytes	(Week 0, week 54) and (week 0, week 80)	Change in monocytes (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Alanine Aminotransferase (ALAT)	(Week 0, week 54) and (week 0, week 80)	Change in ALAT (measured in units per liter \[U/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Albumin	(Week 0, week 54) and (week 0, week 80)	Change in albumin (measured in gram per deciliter \[g/dL\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Amylase	(Week 0, week 54) and (week 0, week 80)	Change in amylase (measured in units per liter \[U/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Alkaline Phosphatase (ALP)	(Week 0, week 54) and (week 0, week 80)	Change in ALP (measured in units per liter \[U/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Aspartate Aminotransferase (ASAT)	(Week 0, week 54) and (week 0, week 80)	Change in ASAT (measured in units per liter \[U/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Total Bilirubin	(Week 0, week 54) and (week 0, week 80)	Change in Total bilirubin (measured in micromole per liter \[umol/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Calcium Corrected	(Week 0, week 54) and (week 0, week 80)	Change in calcium corrected (measured in millimole per liter \[mmol/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Chloride	(Week 0, week 54) and (week 0, week 80)	Change in chloride (measured in millimole per liter \[mmol/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Creatine Kinase	(Week 0, week 54) and (week 0, week 80)	Change in creatine kinase (measured in units per liter \[U/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Creatinine	(Week 0, week 54) and (week 0, week 80)	Change in creatinine (measured in micromole per liter \[umol/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Gamma-glutamyl Transferase (GGT)	(Week 0, week 54) and (week 0, week 80)	Change in GGT (measured in units per liter \[U/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: C-reactive Protein Serum	(Week 0, week 54) and (week 0, week 80)	Change in C-reactive protein serum (measured in milligrams per liter \[mg/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Lactate Dehydrogenase	(Week 0, week 54) and (week 0, week 80)	Change in Lactate Dehydrogenase (measured in units per liter \[U/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Lipase	(Week 0, week 54) and (week 0, week 80)	Change in lipase (measured in units per liter \[U/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Magnesium	(Week 0, week 54) and (week 0, week 80)	Change in magnesium (measured in millimole per liter \[mmol/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Phosphate	(Week 0, week 54) and (week 0, week 80)	Change in phosphate (measured in millimole per liter \[mmol/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Potassium	(Week 0, week 54) and (week 0, week 80)	Change in potassium (measured in millimole per liter \[mmol/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Sodium	(Week 0, week 54) and (week 0, week 80)	Change in sodium (measured in millimole per liter \[mmol/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Total Protein	(Week 0, week 54) and (week 0, week 80)	Change in total protein (measured in gram per liter \[g/dL\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Blood Urea Nitrogen Serum	(Week 0, week 54) and (week 0, week 80)	Change in blood urea nitrogen serum (measured in milligram per deciliter \[mg/dL\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Biochemistry: Uric Acid	(Week 0, week 54) and (week 0, week 80)	Change in Uric Acid (measured in milligram per deciliter \[mg/dL\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in International Normalised Ratio (INR)	(Week 0, week 54) and (week 0, week 80)	Change in INR (measured in ratio\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in D-Dimer	(Week 0, week 54) and (week 0, week 80)	Change in D-Dimer (measured in mg/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Lipids: Total Cholesterol (Ratio to Baseline)	(Week 0, week 54) and (week 0, week 80)	Change in total cholesterol (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Lipids: Free Fatty Acids (Ratio to Baseline)	(Week 0, week 54) and (week 0, week 80)	Change in total free fatty acids (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Lipids: HDL Cholesterol (Ratio to Baseline)	(Week 0, week 54) and (week 0, week 80)	Change in HDL cholesterol (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Lipids: LDL Cholesterol (Ratio to Baseline)	(Week 0, week 54) and (week 0, week 80)	Change in LDL cholesterol (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Lipids: Triglycerides (TG) (Ratio to Baseline)	(Week 0, week 54) and (week 0, week 80)	Change in Triglycerides (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Total Immunoglobulin E (IgE)	(Week 0, week 54) and (week 0, week 80)	Change in IgE (measured in kilo international units per liter \[kIU/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Urinalysis: Urine Dipsticks	Week 0, week 54 and week 80	Urinalysis was performed by urine dipsticks for protein, glucose, erythrocytes, ketones leukocytes, nitrite, pH and specific gravity and categorised as normal, abnormal not clinically significant (NCS) and abnormal clinially significant (CS). Number of participants in each category at baseline (week 0), week 54 and 80 are presented.
Change in Cytokines: Interleukin (IL)-6	Week 0, week 54 and week 80	IL-6 levels at baseline (week 0), weeks 54 and 80 are evaluated and presented.
Change in Cytokines- Interleukin (IL)-10	Week 0, week 54 and week 80	IL-10 levels at baseline (week 0), weeks 54 and 80 are evaluated and presented.
Change in Cytokines: Interleukin (IL)-17	Week 0, week 54 and week 80	IL-17 levels at baseline (week 0), weeks 54 and 80 are evaluated and presented.
Change in Cytokines: Interferon (IFN) Gamma	Week 0, week 54 and week 80	IFN gamma levels at baseline (week 0), weeks 54 and 80 are evaluated and presented.
Change in Cytokines: TNF-alpha	Week 0, week 54 and week 80	TNF-alpha levels at baseline (week 0), weeks 54 and 80 are evaluated and presented.
Change in Hormone Level: Thyroid Stimulating Hormone (TSH)	(Week 0, week 54) and (week 0, week 80)	Change in TSH (measured in milli international units per liter \[mIU/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Hormone Level: Calcitonin	(Week 0, week 54) and (week 0, week 80)	Change in Calcitonin (measured in nanogram per liter \[ng/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Systolic and Diastolic Blood Pressure	(Week 0, week 54) and (week 0, week 80)	Change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) are evaluated from baseline (week 0) to weeks 54 and 80.
Change in Pulse	(Week 0, week 54) and (week 0, week 80)	Change in pulse is evaluated from baseline (week 0) to weeks 54 and 80
Change in Body Temperature	Week 0, week 54) and (week 0, week 80)	Change in body temperature is evaluated from baseline (week 0) to weeks 54 and 80.
Change in Respiratory Rate	(Week 0, week 54) and (week 0, week 80)	Change in respiratory rate is evaluated from baseline (week 0) to weeks 54 and 80.
Change in Electrocardiogram (ECG)	Week 0, week 54 and week 80	The ECG was assessed by the investigator at baseline (week 0), week 54 and week 80 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline, week 54 and week 80 are presented.
Change in Eye-examination	Week 0, week 54 and week 80	Dilated fundoscopy or fundus photography was performed by the investigator at week 0, week 54 and week 80. The results of the examination were interpreted for each eye (left/right) are categorised as normal, abnormal NCS or abnormal CS. Number of participants in each category at week 0, week 54 and week 80 are presented.
Change in Physical Examination	Week 0, week 54 and week 80	Physical examination parameters are categorised as general appearance; head, ears, eyes, nose, throat, neck; respiratory system;cardiovascular system; gastrointestinal system including mouth; musculoskeletal system; central and peripheral nervous system; skin; lymph node palpation and thyroid gland. Investigator assessed the participants with normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) findings at week 0, week 54 and week 80 are presented.
Occurrence of Anti-NNC0114-0006 Antibodies	Week 0, week 54 and week 80	This outcome measure was applicable for NNC0114-0006 + Liraglutide treatment arm and NNC0114-0006 treatment arm. Participants was assessed for anti-NNC0114-0006 antibodies. Participant who reported anti-NNC0114-0006 antibodies were further analyzed for cross-reactivity. Number of participants who measured with anti-NNC0114-0006 antibodies at week 54 and week 80 are presented.
Occurrence of Anti-liraglutide Antibodies	Week 0, week 54 and week 80	This outcome measure is applicable for NNC0114-0006 + Liraglutide treatment arm and Liraglutide treatment arm. Participants was assessed for anti-liraglutide antibodies. Participant who reported anti-liraglutide antibodies were further analyzed for cross-reactivity. Number of participants who measured with anti-liraglutide antibodies at week 54 and week 80 are presented.
Change in Insulin Dose	(Week 0, week 54) and (week 0, week 80)	The total daily insulin dose was derived as the average of the doses reported on the three days prior to the visit. Change in daily total insulin dose from baseline (week 0) after 54 weeks of treatment and week 80 are presented.
Change in Number of Insulin Injections	(Week 0, week 54) and (week 0, week 80)	The number of insulin injections was derived as the average of the reported number on the three days prior to the visit. The change in number of insulin injections per day (count) from baseline (week 0) after 54 weeks of treatment and week 80 are presented.
Number of Weeks Off Bolus Insulin	(Week 0 to week 54) and (week 0 to week 80)	The number of weeks off bolus insulin after 54 weeks of treatment and week 80 are presented.
Change in HbA1c	(Week 0, week 54) and (week 0, week 80)	Change in glycosylated haemoglobin (HbA1c) is evaluated from baseline (week 0) to weeks 54 and 80.
Change in Fasting Plasma Glucose	(Week 0, week 54) and (week 0, week 80)	Change in fasting plasma glucose is evaluated from baseline (week 0) to weeks 54 and 80.
Change in Fasting C-peptide- Ratio to Baseline	(Week 0, week 54) and (week 0, week 80)	Change in fasting C-peptide (measured in nanomole per liter \[nmol/L\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
Change in Fasting Glucagon- Ratio to Baseline	(Week 0, week 54) and (week 0, week 80)	Change in fasting glucagon (measured in picogram per milliliter \[pg/mL\]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.
7-point SMPG Profiles	Week 54 and Week 80	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime. 7-point SMPG profile values are presented for week 54 and week 80.
Change in 7- Points Self-measured Plasma Glucose (SMPG) Postprandial Glucose /Prandial Increment: Breakfast, Lunch, Dinner	(Week 0, week 54) and (week 0, week 80)	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime. Change from baseline (week 0) to week 54 and week 80 in 7-point SMPG postprandial glucose /prandial increment (breakfast, lunch and dinner) value are presented.
Change in 7- Points Self-measured Plasma Glucose (SMPG) Postprandial Glucose /Prandial Increment (Average Over the Three Meals)	(Week 0, week 54) and (week 0, week 80)	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime. Change from baseline (week 0) to week 54 and week 80 in 7-point self-measured plasma glucose (SMPG) postprandial glucose /prandial increment (average over the three meals) value is presented.
Change in Mean of 7-point Profiles	(Week 0, week 54) and (week 0, week 80)	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime. Change from baseline (week 0) to week 54 and week 80 in mean of 7-point profiles value is presented.
Before Breakfast 7- Points Self Measured Plasma Glucose (SMPG)	Week 54 and week 80	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime. Before breakfast 7-point self-measured plasma glucose (SMPG) profile values are presented at week 54 and week 80.
Area Under the NNC0114-0006 Concentration-time Curve Over a Dosing Interval at Steady State (AUCtau, NNC0114-0006)	Pre-dose and 1 hour post-dose during week 48 to week 54	AUCtau, NNC0114-0006 was derived as the area under the concentration-time curve using the linear trapezoidal technique based on observed values and actual measurement times between 0 and 6 weeks (after the last dose). This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.
Terminal Half-life (t½) After Last Dose of NNC0114-0006	Pre-dose and 1 hour post-dose during week 48 to week 80	Terminal half life was calculated as log(2)/λz. The terminal rate constant λz was determined through linear regression with the logarithm to concentration as the response variable and actual measurement time as the explanatory variable. Valid observations from the terminal part of the curve, which is approximately linear, were used for the determination. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.
Apparent Volume of Distribution of NNC0114-0006 at Steadystate (Vss, NNC0114-0006)	Pre-dose and 1 hour post-dose during week 48 to week 80	The apparent volume of distribution of NNC0114-0006 at steady-state was calculated as mean residence time of (MRT) of NNC0114-0006 multiplied by clearance of NNC0114-0006 at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.
Clearance of NNC0114-0006 at Steady State (CLss, NNC0114-0006)	Pre-dose and 1 hour post-dose during week 48 to week 54	Clearance of NNC0114-0006 at steady state was calculated as dose/AUCtau, NNC0114-0006. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.
Mean Residence Time of NNC0114-0006 (MRT, NNC0114-0006)	Pre-dose and 1 hour post-dose during week 48 to week 80	This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms. Mean residence time of NNC0114-0006 is presented.
Accumulation Ratio of NNC114-0006 (RA,AUC, NNC0114-0006)	Pre-dose and 1 hour post-dose during (week 0 to week 6) and (week 48 to week 54)	Accumulation ratio of NNC114-0006 was defined as AUC48-54 weeks/AUC0-6 weeks. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.
Observed NNC0114-0006 Concentration Prior to Dosing of NNC0114-0006 at Steady State (Ctrough, NNC0114-0006)	Week 48 (predose)	Ctrough of NNC0114-0006 was defined as concentration prior to dosing of NNC0114-0006 at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.
Observed NNC0114-0006 Concentration 1 Hour After Dosing of NNC0114-0006 at Steady State (C1h, NNC0114-0006)	Week 48 (1 hour post-dose)	C1h, NNC0114-0006 was defined as concentration of NNC0114-0006 at 1 hour after dosing of NNC0114-0006 at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.
Liraglutide Concentration at Steady State (C Liraglutide)	Week 54 (post-dose)	C liraglutide was defined as the liraglutide concentration at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and Liraglutide treatment arms.
Change in Biomarker: Immune Phenotyping- B Cell Panel	Week 0, week 54 and week 80	B cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80. In below table CD refer to Cluster of Differentiation; IgMNeg refers to Immunoglobulin M negative; IgDNeg refers to Immunoglobulin D negative.
Change in Biomarker: Immune Phenotyping- Natural Killer (NK) Cell Panel	Week 0, week 54 and week 80	NK cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80. In below table ADCC refer to Antibody-dependent cellular cytotoxicity; CD refer to Cluster of Differentiation.
Change in Biomarker: Immune Phenotyping- T Cell Panel	Week 0, week 54 and week 80	T cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80. In below table CD refer to Cluster of Differentiation; TEMRA refers to terminally differentiated effector memory cells re-expressing CD45RA; CCR refers to C-C chemokine receptor; TREG refers to Regulatory T cells.
Change in Biomarker: Immune Phenotyping- T Follicular Helper (TfH) Cell Panel	Week 0, week 54 and week 80	TfH cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80. In below table CTFH refer to Circulating T follicular helper; ICOS refers to inducible T-cell co-stimulator; PD refers to Programmed cell death protein; CCR refers to C-C chemokine receptor; CXCR refers to C-X-C chemokine receptor; CD refer to Cluster of Differentiation; CM refers to central memory; EM refers to effector memory, TIGIT refers to T cell immunoreceptor with Ig and ITIM domains.
Change in Biomarker: Immune Phenotyping- Myeloid Cell Panel	Week 0, week 54 and week 80	Myeloid panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80. In below table HLA refers to Human Leukocyte Antigen; MDSC refers to myeloid-derived suppressor cell; DC refers to Dendritic cells; MYDC refers to Myeloid Dendritic Cells; IMMYE_MDSC refers to Immature myeloid cells \& a subset of myeloid suppressor cells within the CD14-HLA class II- myeloid cell population.
Autoantibodies Against Glutamic Acid Decarboxylase (GAD)	Week 0, week 54 and week 80	Participants were analyzed for autoantibodies against Glutamic acid decarboxylase (GAD) and were categorized as negative and positive.
Autoantibodies Against Zinc-transporter 8 (ZnT8)	Week 0, week 54 and week 80	Participants were analyzed for autoantibodies against Zinc-transporter 8 (ZnT8) and were categorized as negative and positive.
Autoantibodies Against Islet Antigen-2 (IA2)	Week 0, week 54 and week 80	Participants were analyzed for autoantibodies against Islet antigen-2 (IA2) and were categorized as negative and positive.
Autoantibodies Against Insulin Autoantibodies (IAA)	Week 0, week 54 and week 80	Participants were analyzed for autoantibodies against Insulin autoantibodies (IAA) and were categorized as negative and positive.
Change in Biomarker: Total Interleukin-21 (IL-21)	Week 0, week 54 and week 80	IL-21 is evaluated at baseline (week 0), week 54 and week 80.
Change in Biomarker: Serum Vitamin D (1,25 Dehydroxy-calciferol)	Week 0, week 54 and week 80	Serum vitamin D is evaluated at baseline (week 0), week 54 and week 80.
Change in Short Form 36 Health Survey (SF-36)	(Week 0, week 54) and (week 0, week 80)	SF-36v2™ questionnaire measured the HRQoL on 8 domains (Bodily Pain, General Health, Mental Health, Physical Functioning, Role Emotion, Physical Health, Social Functioning and Vitality) on individual scale ranges. 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. Change from baseline (week 0) to week 54 and week 80 in SF-36 score is presented.The MCS measure is derived from domain scales of vitality, social functioning, role emotional and mental health. The PCS measure is derived from domain scales of physical functioning, role-physical, bodily pain, and general health. 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. A positive change score indicate an improvement since baseline.
Change in Experience of Treatment Benefits and Barriers (ETBB)	(Week 0, week 54) and (week 0, week 80)	Treatment Benefits and Barriers (ETBB) questionnaire measured diabetes-specific health beliefs on 2 categories: Total Score for Perceived Barriers and Perceived Benefits. The measurement of perceived benefits of, and barriers to, treatment was achieved by creating a pool 28 statements each with a 7-point scale ranging from strongly agree (6) to strongly disagree (0). ETBB benefits score was calculated using the responses from questions 1, 4, 7, 8, 10, and 12 and ETBB barriers score was calculated using the responses from questions 2, 3, 5, 6, 9, and 11. Both was calculated as the sum of responses divided by number of responses received multiplied by the maximum number of responses. Based on the responses used the maximum responses available was 6. The higher score indicates more perceived benefits or more perceived barrier.
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ)	(Week 0, week 54) and (week 0, week 80)	Change from baseline (week 0) in DTSQ is evaluated at week 54 and 80. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher score indicates a higher level of glycaemia/treatment satisfaction.
Area Under the Concentration-time Curve (AUC) 0-4h of Mixed Meal Tolerance Test (MMTT) Stimulated C-peptide at Week 80 Relative to Baseline	0 - 4 hours post-dose on week 0 and week 80	Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a mixed meal tolerance test (MMTT) stimulated C-peptide at week 80 is presented as ratio to baseline. AUC of C-peptide was measured as Nano moles\hour per liter (nmol\h/L).
AUC0-2h of C-peptide at Week 80 Relative to Baseline	0-2 hours post-dose on week 0 and week 80	Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated C-peptide at week 80 is presented as ratio to baseline. AUC of C-peptide was measured as 'nmol\*h/L'.
Cmax of C-peptide at Week 80 Relative to Baseline	0-4 hours post-dose on week 0 and week 80	Maximum observed concentration (Cmax) of a MMTT stimulated C-peptide at week 80 is presented as ratio to baseline. Cmax of C-peptide was measured as nanomoles per liter (nmol/L).
AUC0-4h of Glucose at Week 80 Relative to Baseline	0 - 4 hours post-dose on week 0 and week 80	Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a MMTT stimulated glucose at week 80 is presented as ratio to baseline. AUC of glucose was measured as Milli moles\hour per liter (mmol\h/L).
AUC0-2h of Glucose at Week 80 Relative to Baseline	0-2 hours post-dose on week 0 and week 80	Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated glucose at week 80 is presented as ratio to baseline. AUC of glucose was measured as 'mmol\*h/L'.
Cmax of Glucose at Week 80 Relative to Baseline	0-4 hours post-dose on week 0 and week 80	Maximum observed concentration (Cmax) of a MMTT stimulated glucose at week 80 is presented as ratio to baseline. Cmax of C-peptide was measured as 'mmol/L'.