The Efficacy and Safety of Liraglutide as Adjunct Therapy to Insulin in the Treatment of Type 1 Diabetes

Study Overview
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Brief Summary
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This trial is conducted globally. The aim of the trial is to confirm the efficacy and safety of liraglutide as adjunct therapy to insulin in the treatment of type 1 diabetes. The total trial duration per subject is approximately 58 weeks.

Official Title
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The Efficacy and Safety of Liraglutide as Adjunct Therapy to Insulin in the Treatment of Type 1 Diabetes. A 52-week Randomised, Treat-to-target, Placebo-controlled, Double Blinded, Parallel Group, Multinational, Multi-centre Trial

Conditions
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Diabetes, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: liraglutide
* Drug: placebo
* Drug: liraglutide
* Drug: placebo
* Drug: liraglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Informed consent obtained - Type 1 diabetes mellitus for 12 months or longer - Basal bolus or CSII (Continuous Subcutaneous Insulin Infusion, insulin pump) treatment for 6 months or longer - Stable insulin treatment for the last 3 months prior to Screening, as judged and documented by the investigator - HbA1c 7.0-10% (Diabetes Control and Complications Trial (DCCT)), both inclusive, (corresponding to 53-86 mmol/mol (International Federation of Clinical Chemistry (IFCC)) - Ability and willingness to comply with all protocol procedures e.g. correct handling of trial product, complete trial related questionnaires, diaries, self-monitoring of plasma glucose, self titration of insulin and attend all scheduled visits Exclusion Criteria: - Prior use of glucagon-like peptide-1 (GLP-1) receptor agonist or dipeptidyl peptidase IV (DPP-4) inhibitors - Use of any medication, which in the investigator's opinion could interfere with the glycaemic control or affect the subject's safety.Premix insulin is not allowed - Known proliferative retinopathy or maculopathy requiring acute treatment - Severe neuropathy, in particular autonomic neuropathy, i.e. gastroparesis, as judged by the investigator - Uncontrolled/ untreated blood pressure at screening above 160 mmHg for systolic or above 100 mmHg for diastolic - History of acute or chronic pancreatitis - Screening calcitonin value equal to or above 50 ng/L - Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia type 2 (MEN2) - Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide 0.6 mg + insulin<br> | Drug: liraglutide<br>* Subjects randomised to 0.6 mg liraglutide treatment or liraglutide placebo as an add-on to their pre-trial insulin treatment will remain on this dose throughout the study (52 weeks). Administered subcutaneously (s.c., under the skin) once daily.<br>|
| Experimental: Liraglutide 1.2 mg + insulin<br> | Drug: liraglutide<br>* Subjects randomised to 0.6 mg liraglutide treatment or liraglutide placebo as an add-on to their pre-trial insulin treatment will remain on this dose throughout the study (52 weeks). Administered subcutaneously (s.c., under the skin) once daily.<br>|
| Experimental: Liraglutide 1.8 mg + insulin<br> | Drug: liraglutide<br>* Subjects randomised to 0.6 mg liraglutide treatment or liraglutide placebo as an add-on to their pre-trial insulin treatment will remain on this dose throughout the study (52 weeks). Administered subcutaneously (s.c., under the skin) once daily.<br>|
| Placebo Comparator: Liraglutide placebo 0.6 mg + insulin<br> | Drug: placebo<br>* Subjects randomised to 0.6 mg liraglutide treatment or liraglutide placebo as an add-on to their pre-trial insulin treatment will remain on this dose throughout the study (52 weeks). Administered subcutaneously (s.c., under the skin) once daily.<br>|
| Placebo Comparator: Liraglutide placebo 1.2 mg + insulin<br> | Drug: placebo<br>* Subjects randomised to 0.6 mg liraglutide treatment or liraglutide placebo as an add-on to their pre-trial insulin treatment will remain on this dose throughout the study (52 weeks). Administered subcutaneously (s.c., under the skin) once daily.<br>|
| Placebo Comparator: Liraglutide placebo 1.8 mg + insulin<br> | Drug: placebo<br>* Subjects randomised to 0.6 mg liraglutide treatment or liraglutide placebo as an add-on to their pre-trial insulin treatment will remain on this dose throughout the study (52 weeks). Administered subcutaneously (s.c., under the skin) once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (Glycosylated Haemoglobin) | Change from baseline in HbA1c at week 52. Missing values were handled by using a mixed model for repeated measurements (MMRM). | Week 0, week 52 | 
| Change From Baseline in Body Weight | Change from baseline in body weight at week 52. Missing values were handled by using a MMRM. | Week 0, week 52 | 
| Change From Baseline in Total Daily Insulin Dose | Change from baseline in total daily insulin dose at week 52. Change from baseline was represented in terms of ratio to baseline for insulin dose i.e. Total daily insulin dose at week 52/total daily insulin dose at baseline. Missing values were handled by using a MMRM. | Week 0, week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment-emergent Symptomatic Hypoglycaemic Episodes | This is a confirmatory secondary endpoint. Symptomatic hypoglycaemic episodes were defined as: 1) Severe according to the American Diabetes Association (ADA) classification: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. OR 2) Self-monitoring of plasma glucose value of <3.1 mmol/L, with symptoms consistent with hypoglycaemia. A treatment emergent episode is defined as an episode with onset date (or increase in severity) on or after first day of exposure to randomised treatment and up to last dose + 7 days. | Weeks 0-52 |