Study of Effectiveness of Liraglutide Added to High Dose Insulin in Type II Diabetics

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of adding liraglutide to high dose insulin therapy compared to high dose insulin therapy alone in patients with insulin-treated Type 2 diabetes with insulin requirements of > 100 units of insulin per day.

Detailed Description
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40 subjects with Type 2 diabetes using > 100 units of insulin per day with or without metformin with HbA1c > 6.5% will be randomized into 2 treatment groups: treatment group will have liraglutide added to insulin and control group will have insulin uptitration only for 6 months. Primary endpoint to be compared between groups will be HbA1c at 6 months. Secondary endpoints will include weight, total daily insulin dose, percent time in euglycemic, hyperglycemic, and hypoglycemic ranges by continuous glucose monitor (CGM), and effect on GlycoMark and hs-CRP. Safety endpoints will include incidence of hypoglycemia and incidence of gastrointestinal side effects.

Official Title
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Liraglutide and Insulin-001 A Randomized Prospective Trial of Liraglutide Added to High-Dose Insulin Therapy vs. High-Dose Insulin Therapy Alone in Insulin-Resistant Patients With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type II

Intervention / Treatment
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* Drug: Liraglutide
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients with Type 2 diabetes with HbA1c from 6.5 to 10% treated with intensive insulin therapy (MDI or CSII, including U-500 insulin-treated patients) using > 100 units of insulin, with or without a stable dose of oral insulin sensitizing medications, for at least three months. Aged 18 to 80 years. Females of child-bearing potential must be using adequate form of contraception. Patient willing to monitor BG four times daily, use CGM, and comply with study-related protocol. Exclusion Criteria: Type 1 diabetes. Use of any GLP-1 receptor agonist within previous three months. Use of DPP-4 inhibitors or oral insulin secretagogues within the previous three months. Use of glucocorticoids (except inhaled). Use of any experimental drug within previous three months. Known or suspected allergy to liraglutide, Novolog or Levemir. Personal or family history of medullary carcinoma of the thyroid or MEN-2. Concomitant chronic renal disease with creatinine > 1.5%. Concomitant chronic hepatic, gastrointestinal or other illness (including pancreatitis or active cardiovascular disease except stable exertional angina). Inability or unwillingness to monitor BG, use CGM, or comply with study protocol. Women of child-bearing potential unwilling to use adequate contraception, intending to become pregnant or breast-feeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: liraglutide plus insulin<br>Patients were randomized to receive liraglutide plus insulin (LIRA) for 12 months. | Drug: Liraglutide<br>* SC, 1.8mg,QD, six months to one year<br>* Other names: Victoza;Drug: Insulin<br>* SC, will be titrated during the study, 4 times a day, 1 year<br>* Other names: Novolog;|
| Active Comparator: Insulin titration only<br>Patients were randomized to receive insulin only (control) for 6 months. The controls were then crossed over to receive liraglutide plus insulin for 6 months after the initial control period. | Drug: Insulin<br>* SC, will be titrated during the study, 4 times a day, 1 year<br>* Other names: Novolog;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HbA1c at six months | Glycemic control as measured by HbA1c | baseline and six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypoglycemia | The frequency and severity of hypoglycemia in each treatment arm by glucose meter download and by percent time spent in the hypoglycemic range (BG < 70 mg/dl) by CGM will be assessed at six and 12 months | 6 months and 12 months | 
| Total Daily Insulin Dose (TDID) | TDID will be determined in each treatment arm for statistical comparisons at three and six months, and for entire cohort at nine and 12 months. | 3, 6, 9, and 12 months | 
| Weight | Weight will be statistically compared to baseline and between treatment arms at three and six months, and for entire cohort between baseline, six, nine and 12 months. | baseline, 3, 6, 9, and 12 months | 
| GlycoMark | Postprandial glycemic control as assessed by GlycoMark and CGM will be compared between study groups at three and six months, and for entire cohort compared to baseline at nine and 12 months. | baseline, 3, 6, 9, and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insulin, Type II Diabetes, liraglutide, Glucagon-Like Peptide 1