LIraglutide and Beta-cell RepAir (LIBRA) Study

Study Overview
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Brief Summary
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Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by progressive deterioration in the function of the pancreatic beta-cells, which are the cells that produce and secrete insulin (the hormone primarily responsible for the handling of glucose in the body). We propose a double-blind, randomized controlled study comparing the effect of liraglutide (a novel anti-diabetic drug with beta-cell protective potential) versus placebo, on the preservation of beta-cell function over one year in patients with T2DM. This study may demonstrate an important beta-cell protective capacity of liraglutide.

Detailed Description
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In this study, patients with type 2 diabetes who meet randomization criteria will be randomized to either liraglutide or placebo, with serial assessment of beta-cell function over 48 weeks follow-up. The hypothesis under study is whether liraglutide can preserve beta-cell function.

Official Title
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A Randomized Controlled Study Assessing the Effect of Liraglutide on the Preservation of Beta-Cell Function in Patients With Type 2 Diabetes Mellitus: The LIraglutide and Beta-cell RepAir (LIBRA) Study

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Liraglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: men and women between the ages of 30 and 75 years inclusive physician-diagnosed type 2 diabetes of </= 7 years duration negative for anti-GAD antibodies on 0-2 oral anti-diabetic medications A1c at screening between 5.5% and 9.0% inclusive, if on oral anti-diabetic medications, or between 6.0% and 10.0% inclusive, if not on oral anti-diabetic medications Exclusion Criteria: use of insulin, GLP-1 agonist, or dipeptidyl peptidase-4 (DPP-4) inhibitor type 1 diabetes or secondary forms of diabetes major illness with life expectancy < 5 years involvement in another study requiring drug therapy hypersensitivity to insulin, liraglutide, or metformin renal dysfunction hepatic dysfunction history of pancreatitis family or personal history of Multiple Endocrine Neoplasia type 2 (MEN-2) or familial medullary thyroid carcinoma personal history of non-familial medullary thyroid carcinoma malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer) excessive alcohol consumption unwillingness to undergo multiple daily insulin injection therapy unwillingness to perform capillary blood glucose monitoring at least 4 times per day during intensive insulin therapy congestive heart failure pregnancy

Ages Eligible for Study
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Minimum Age: 30 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide<br> | Drug: Liraglutide<br>* Liraglutide administered as once daily sc injection<br>* Other names: Victoza;|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* placebo administered as once daily sc injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preservation of beta-cell function measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2) | ISSI-2 is a validated OGTT-derived measure of beta-cell function analogous to the disposition index obtained from the intravenous glucose tolerance test. ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve (AUCins) to the area-under-the-glucose curve (AUCgluc) and (ii) insulin sensitivity measured by the Matsuda index. | 48-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Control | A1c Fasting glucose, 2 hour glucose, and AUCgluc on OGTT Proportion of participants with A1c <7% at study end Glucose tolerance status at study end (NGT, pre-diabetes, diabetes) Proportion of participants with fasting glucose in non-diabetic range at study end (ie. <7.0 mmol/L) Time to loss of glycemic control | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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beta-cell function, GLP-1 analogue, diabetes