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LIraglutide and Beta-cell RepAir (LIBRA) Study

Phase 3
Completed
Conditions
Type 2 Diabetes
Interventions
Drug: placebo
Registration Number
NCT01270789
Lead Sponsor
Mount Sinai Hospital, Canada
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
63
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placeboplacebo-
LiraglutideLiraglutide-
Primary Outcome Measures
NameTimeMethod
Preservation of beta-cell function measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2)48-weeks

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.

Secondary Outcome Measures
NameTimeMethod
Glycemic Control48 weeks

* 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

Trial Locations

Locations (1)

Mount Sinai Hospital

🇨🇦

Toronto, Ontario, Canada

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