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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type II
• Intervention / Treatment: Drug: Liraglutide; Drug: Insulin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Mountain Diabetes and Endocrine Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. Aged 18 to 80 years.
3. Females of child-bearing potential must be using adequate form of contraception.
4. Patient willing to monitor BG four times daily, use CGM, and comply with study-related protocol.

Exclusion Criteria:

1. Type 1 diabetes.
2. Use of any GLP-1 receptor agonist within previous three months.
3. Use of DPP-4 inhibitors or oral insulin secretagogues within the previous three months.
4. Use of glucocorticoids (except inhaled).
5. Use of any experimental drug within previous three months.
6. Known or suspected allergy to liraglutide, Novolog or Levemir.
7. Personal or family history of medullary carcinoma of the thyroid or MEN-2.
8. Concomitant chronic renal disease with creatinine > 1.5%.
9. Concomitant chronic hepatic, gastrointestinal or other illness (including pancreatitis or active cardiovascular disease except stable exertional angina).
10. Inability or unwillingness to monitor BG, use CGM, or comply with study protocol.
11. Women of child-bearing potential unwilling to use adequate contraception, intending to become pregnant or breast-feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: liraglutide plus insulin; Patients were randomized to receive liraglutide plus insulin (LIRA) for 12 months.	Drug: Liraglutide; SC, 1.8mg,QD, six months to one year; Other Names: Victoza; Drug: Insulin; SC, will be titrated during the study, 4 times a day, 1 year; Other Names: Levemir; Novolog; U-500
Active Comparator: Insulin titration only; 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; SC, will be titrated during the study, 4 times a day, 1 year; Other Names: Levemir; Novolog; U-500

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mountain Diabetes and Endocrine Center

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: December 16, 2011
• First Submitted That Met QC Criteria: July 30, 2012
• First Posted (Estimate): July 31, 2012

Study Record Updates

• Last Update Posted (Actual): February 25, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Type II Diabetes; insulin; Glucagon-Like Peptide 1; liraglutide
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: high dose and lira 001