Liraglutide in Adolescents With Type 1 Diabetes

Phase 3

Completed

Conditions: Type 1 Diabetes

Interventions: Drug: Liraglutide

Registration Number: NCT02516657

Lead Sponsor: University at Buffalo

Brief Summary: The purpose of this study is to study the effect of a liraglutide, a glucagon-like peptide agonist, on post-meal blood glucose concentrations, glucagon levels, mean weekly blood sugars, and insulin doses in adolescents with Type 1 diabetes. Type 1 diabetes is an autoimmune disease that is usually diagnosed before the age of 20. Individuals with this disease are completely dependent on insulin for survival. While significant advances have been made in technological support for improving diabetes control, insulin remains the only effective treatment for Type 1 diabetes. Liraglutide is a long-acting glucagon-like peptide-1 analog. This drug is approved for the treatment of Type 2 diabetes in adults. This study will test the effect of liraglutide on blood sugar control in adolescents with Type 1 diabetes.

Detailed Description: Type 1 diabetes (T1DM) affects approximately 1:500 children and represents the major form of diabetes in the pediatric population (1). Diagnosis of T1DM is based on symptoms consistent with hyperglycemia (polyuria, polydipsia, and weight loss) and elevated blood sugars. Diagnosis of T1DM is confirmed by measuring serum autoantibodies against insulin and other beta-cell proteins. Subcutaneous insulin is the mainstay of diabetes care; however, ability to achieve optimal glycemic control is impacted by multiple factors including diet, exercise, and psychosocial barriers.

The Diabetes Control and Complications Trial and follow-up EDIC trial were landmark studies demonstrating that improving glycemic control significantly reduces the risk of both micro and macro-vascular disease (2). While technologic advances in blood sugar monitoring, insulin analogs and insulin delivery devices have been made, it is estimated that less than 40% of individuals meet recommended glycemic standards as set forth by the American Diabetes Association; these estimates may be lower in the pediatric population. Thus, adjuvant pharmacologic therapies that improve glycemic control are being tested in patients with T1DM.

Incretin hormones are a class of intestinal peptides that are released in response to nutrient intake (3). The best described incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones act at the level of direct stimulation of pancreatic β-cell function and through extra-pancreatic mechanisms. They primarily potentiate glucose-dependent insulin secretion from the β-cell; other β-cell effects include increasing insulin biosynthesis, stimulating β-cell replication, and preventing apoptosis. Secondary effects of incretin hormones include suppression of glucagon secretion, inhibition of gastric emptying, and potentiation of hepatic glucose uptake (3).

Currently, there are two GLP-1 analogs approved by the Food and Drug Adminstration as adjuvant treatment of Type 2 diabetes mellitus in adults (\> 18 years) who fail to reach glycemic targets with metformin and/or oral hypoglycemic agents. The two drugs - exenatide (BID) and liraglutide (QD) are administered subcutaneously. They have been demonstrated to improve glycemic control in this population and, in some individuals, lead to sustained weight loss.

This study aims to determine whether acute exposure to liraglutide decreases the mean weekly blood glucose levels in adolescents with T1DM. In addition, we will determine whether liraglutide decreases glucose excursions following a meal challenge. The overall hypothesis to be tested is that short-term exposure (7 days) to liraglutide improves glycemic control in adolescents/young adults with T1DM treated with continuous subcutaneous insulin infusion.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 5

Inclusion Criteria

Diagnosis of Type 1 Diabetes Mellitus greater than 1 year
Insulin regimen - continuous subcutaneous insulin infusion with continuous glucose monitoring device
HbA1c <10%

Exclusion Criteria

Previous exposure to liraglutide
History of abdominal surgery
Gastrointestinal reflux disease
History of acute or chronic pancreatitis
History of alcohol abuse or unwillingness to abstain from alcohol during the study
History of thyroid cancer
Family history of Multiple Endocrine Neoplasia 2B syndrome
Pregnant/breastfeeding females
Individuals with antibody-negative insulin requiring diabetes that is consistent with Monogenic Diabetes of Youth
Individuals with steroid induced or cystic fibrosis related diabetes

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Liraglutide 0.6 mg	Liraglutide	Liraglutide 0.6 mg daily injection x 7 days

Primary Outcome Measures

Name	Time	Method
Mean Weekly Blood Glucose	Visit 1 (Before Liraglutide) at baseline (Day 0) vs. Visit 2 (After Liraglutide) on Day 7;	The primary outcome is to determine whether liraglutide decreases mean weekly blood glucose (mean mg/dL glucose as measured by continuous glucose monitor readings) in adolescents with Type 1 diabetes

Secondary Outcome Measures