Safety and Efficacy of Liraglutide in Combination With an OAD in Subjects With Type 2 Diabetes Insufficiently Controlled on OAD Alone

Study Overview
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Brief Summary
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This trial was conducted in Japan. The aim of this trial was to evaluate the safety and efficacy of once daily administration of liraglutide in combination with an oral anti-diabetic drug (OAD) in Japanese subjects with type 2 diabetes who are insufficiently controlled on OAD monotherapy. All subjects will continue their pre-trial OAD (either glinide, metformin, alpha-glucosidase inhibitor or thiazolidinedione) during the trial at unchanged type and dose.

Official Title
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A 52-week, Multi-centre, Open-labelled, Randomised (2:1), Parallel-group Trial With an Active Control (Two OADs Combination Therapy) to Evaluate the Safety and Efficacy of Liraglutide in Combination With an OAD in Subjects With Type 2 Diabetes Insufficiently Controlled on OAD Monotherapy

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: liraglutide
* Drug: oral anti-diabetic drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject.) Japanese subjects with type 2 diabetes on monotherapy with an OAD (either glinide, metformin, a-glucosidase inhibitor or thiazolidinedione) within approved Japanese labelling in addition to diet and exercise therapy. Total daily dose and type of drug should have remained unchanged for at least 8 weeks prior to Visit 1 Type 2 diabetes mellitus (clinically diagnosed) for at least 6 months HbA1c between 7.0-10.0% (both inclusive) Body Mass Index (BMI) below 40.0 kg/m^2 Outpatients who have no plans for an educational hospitalisation for the purpose of glycaemic control. However, hospitalisation for training of self-injection from Visit 2 that is for no longer than one week is allowed Subjects able and willing to perform self-monitoring of plasma glucose (SMPG) Exclusion Criteria: Subjects with known or previous malignant tumor and are strongly suspected of recurrence (except basal cell skin cancer or squamous cell skin cancer) Calcitonin above or equal to 160 pg/mL Personal history of non-familial medullary thyroid carcinoma Family or personal history of multiple endocrine neoplasia type 2 (MEN-2) or familial medullary thyroid carcinoma (FMTC) History of chronic pancreatitis or idiopathic acute pancreatitis Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months Treatment with GLP-1 receptor agonist or dipeptidyl peptidase 4 (DPP-4) inhibitor within 12 weeks prior to Visit 1 Having contraindications to liraglutide and any of the OADs (according to Japanese labelling)

Ages Eligible for Study
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Minimum Age: 20 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide + an OAD therapy<br> | Drug: liraglutide<br>* 0.9 mg/day liraglutide was injected once daily subcutaneously (s.c., under the skin).<br>|
| Active Comparator: Two OADs combination therapy<br> | Drug: oral anti-diabetic drug<br>* An additional oral anti-diabetic drug (OAD) with a different mechanism of action than the pre-trial OAD. The type and dosage of the additional OAD should be chosen by the investigator within the Japanese labelled dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (AEs) | Adverse events were defined as events occurring after administration of trial product and no later than 7 days after last day of treatment. Severe AEs: considerable interference with subject's daily activities. Moderate AEs: Marked symptoms, moderate interference with the subject's daily activities. Mild AEs: No or transient symptoms, no interference with the subject's daily activities. Serious AEs: AEs that resulted in any of the following: death, a life-threatening experience, hospitalization/prolongation of existing hospitalization, persistent/significant disability, and congenital anomaly. | Week 0 to Week 52 + 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Confirmed Hypoglycaemic Episodes | Confirmed hypoglycaemic episodes consisted of the pool of episodes of severe hypoglycaemia as well as minor hypoglycaemic episodes [An episode with symptoms consistent with hypoglycaemia with confirmation by plasma glucose <3.1 mmol/L (56 mg/dL) or full blood glucose <2.8 mmol/L (50 mg/dL) and which is handled by the subject himself or herself or any asymptomatic PG value <3.1 mmol/L (56 mg/dL) or full blood glucose value <2.8 mmol/L (50 mg/dL)] with a confirmed plasma glucose value of less than 3.1 mmol/L (56 mg/dL). | Week 0 to Week 52 | 
| Change in HbA1c From Baseline to Week 52 | Estimated mean change in HbA1c from baseline after 52 Weeks of treatment | Week 0, week 52 | 
| Change in FPG From Baseline to Week 52 | Estimated mean change from baseline in FPG after 52 Weeks of treatment | Week 0, week 52 |