Liraglutide in Adolescents With Type 1 Diabetes

Effect of Liraglutide on Glycemic Control, Glucagon Secretion and Inflammatory Markers in Adolescents With Type 1 Diabetes Mellitus

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Liraglutide

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14203
      • UBMD Pediatrics, Division of Pediatric Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liraglutide 0.6 mg; Liraglutide 0.6 mg daily injection x 7 days	Drug: Liraglutide; Liraglutide 0.6 mg; Other Names: Victoza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Weekly Blood Glucose	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	Visit 1 (Before Liraglutide) at baseline (Day 0) vs. Visit 2 (After Liraglutide) on Day 7;

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Daily Insulin Dose	mean U/kg/day over 7 days	Visit 1 (Before Liraglutide) at baseline (Day 0) vs. Visit 2 (After Liraglutide) on Day 7;

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Sugar < 70 mg/dL	Determine whether liraglutide increases episodes of blood sugar <70 mg/dL as measured by glucometer and CGM	Visit 1 (Before Liraglutide) at baseline (Day 0) vs. Visit 2 (After Liraglutide) on Day 7;
Serum Amylase Level	Determine amylase levels before and during liraglutide treatment	Visit 1 (Before Liraglutide) at baseline (Day 0) vs. Visit 2 (After Liraglutide) on Day 7;

Collaborators and Investigators

• Sponsor: University at Buffalo
• Investigators: Principal Investigator: Lucy D Mastrandrea, MD, PhD, University at Buffalo

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2012
• Primary Completion (Actual): August 3, 2022
• Study Completion (Actual): August 3, 2023

Study Registration Dates

• First Submitted: August 4, 2015
• First Submitted That Met QC Criteria: August 4, 2015
• First Posted (Estimated): August 6, 2015

Study Record Updates

• Last Update Posted (Actual): April 20, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: 437619-6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No