Type 2 Diabetes
Conditions
Keywords
beta-cell function, GLP-1 analogue, diabetes
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.
Interventions
DRUGLiraglutide
Liraglutide administered as once daily sc injection
DRUGplacebo
placebo administered as once daily sc injection
Sponsors
Novo Nordisk A/S
Mount Sinai Hospital, Canada
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Glycemic Control | 48 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 |
Countries
Canada
Outcome results
None listed