Efficacy and Safety of Liraglutide Versus Lixisenatide as add-on to Metformin in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of the trial is to investigate the efficacy and safety of liraglutide versus lixisenatide as add-on to metformin in subjects with type 2 diabetes (T2DM).

Official Title
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Efficacy and Safety of Liraglutide Versus Lixisenatide as add-on to Metformin in Subjects With Type 2 Diabetes

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: liraglutide
* Drug: lixisenatide


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 are carried out as part of the trial, including activities to determine suitability for the trial Subjects diagnosed with T2DM and on unchanged metformin treatment at the maximum tolerated dose (at least 1000 mg/day and up to 3000 mg/day) for at least 90 days prior to screening HbA1c 7.5 - 10.5% (53 mmol/mol - 91 mmol/mol) (both inclusive) Body Mass Index (BMI) equal to or above 20 kg/m^2 Exclusion Criteria: Female of child-bearing potential who is pregnant, breast-feeding or intend to become pregnant or is not using adequate contraceptive methods. (Adequate contraceptive measures as required by local law or practice) Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days prior to screening. Exception is short-term treatment (equal to or below 7 days in total) with insulin in connection with intercurrent illness History of chronic pancreatitis or idiopathic acute pancreatitis Screening calcitonin value equal to or above 50 ng/L Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) Impaired liver function, defined as alanine aminotransferase (ALAT) equal to or above 2.5 times upper normal limit (UNL) Impaired renal function defined as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m^2 per Modification of Diet in Renal Disease (MDRD) formula Any episode of unstable angina, acute coronary event, cerebral stroke/transient ischemic attack (TIA) or other significant cardiovascular event as judged by the investigator within 90 days prior to screening Heart failure, New York Heart Association (NYHA) class IV Uncontrolled hypertension (defined as systolic blood pressure equal to or above 180 mmHg and/or diastolic blood pressure equal to or above 100 mmHg) 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

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: Metformin + liraglutide 1.8 mg<br> | Drug: liraglutide<br>* Starting dose of 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day is reached. Administered s.c. (subcutaneously, under the skin) once daily in addition to the subject's stable pre-trial metformin (equal to or above 1000 mg/day and up to 3000 mg/day).<br>|
| Active Comparator: Metformin + lixisenatide 20 microg<br> | Drug: lixisenatide<br>* Starting dose of 10 microg to be administered s.c. once daily, within the hour prior to the first meal of the day or the evening meal in addition to subject's stable pre-trial metformin (equal to or above 1000mg/day and up to 3000mg/day). Dose escalation to 20 microg s.c. once daily from day 15 after randomization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin (HbA1c) From Baseline | Change from baseline in HbA1c after 26 weeks of treatment. | Week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Plasma Glucose (FPG) From Baseline | Change from baseline in FPG after 26 weeks of treatment. | Week 0, week 26 | 
| Change in Body Weight From Baseline | Change from baseline in body weight after 26 weeks of treatment. | Week 0, week 26 | 
| Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no) | Subjects who achieved HbA1c below 7.0% (53 mmol/mol) after 26 weeks of treatment (yes/no). | After 26 weeks of treatment | 
| Subjects Who Achieve HbA1c Equal to or Below 6.5% (48 mmol/Mol) (American Association of Clinical Endocrinologists [AACE] Target) (Yes/no) | Subjects who achieved HbA1c below equal to or below 6.5% (48 mmol/mol) after 26 weeks of treatment (yes/no). | After 26 weeks of treatment | 
| Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain (Yes/no) | Subjects who achieved HbA1c below 7.0% (53 mmol/mol) and no weight gain after 26 weeks of treatment (yes/no). | After 26 weeks of treatment | 
| Number of Treatment Emergent Adverse Events (TEAEs) | A Treatment Emergent Adverse Event (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. Severity was assessed by investigator. | Weeks 0-26 |