Liraglutide as Additional Treatment to Insulin in Patients With Autoimmune Diabetes Mellitus

Effect of Liraglutide as Additional Treatment to Insulin in Patients With Autoimmune Diabetes Mellitus

The purpose of this study is to investigate the therapeutic effect of Liraglutide on autoimmune diabetes.

Study Overview

• Status: Unknown
• Conditions: Type 1 Diabetes Mellitus; Autoimmune Diabetes
• Intervention / Treatment: Drug: Liraglutide; Drug: Insulin

Detailed Description

Autoimmune Diabetes Mellitus (AIDM) is a subtype of diabetes mellitus caused by autoimmune destruction of beta cells in the islet, including Type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA). Insulin has been used as a routine therapy for AIDM to alleviate the hyperglycemic status, yet cannot effectively prevent the progressing destruction of beta cells or preserve its function. Glucagon-like peptide (GLP-1) analog Liraglutide has been tested in large-scale clinical trial to prove its various benefits for beta cells and glucolipid metabolism in Type 2 diabetes and obesity patients. However, its clinical application in AIDM is not well-defined so far. The aim of this study is to investigate the potential use of Liraglutide on glycemic control in AIDM.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Type 1 diabetes according to ADA criteria <3 years.
• Age≥ 18 years.
• Positive for at least one of the anti-islet autoantibodies: GADA, IA2A, ZnT8A
• Fasting or postprandial plasma C-peptide more than 100 pmol/L
• Written informed consent from the patient or family representative

Exclusion Criteria:

• History or family history of medullary thyroid carcinoma or MEN 2 syndrome;
• History of chronic or acute pancreatitis;
• Allergic to liraglutide or any components in Victoza®;
• Hepatic abnormalities (transaminase > 2 times normal);
• Renal impairments (serum creatinine >133 umol/L);
• Cardiovascular diseases (hypertension, coronary heart disease, etc.);
• Presence of acute metabolic disorders; In the case of acute ketone acidosis, with blood ketone over 0.3mmol/L and pH lower than 7.30;
• Any history of malignancy;
• Female patients who are pregnant or breastfeeding; any female who is unwilling to use a reliable and effective form of contraception for 2 years after recruitment;
• Presence of any infectious diseases, including active skin infections, flu, fever, upper or lower respiratory tract infections; those who wish to participate in the study should keep the infection under control for at least 1 week before receiving Treg product infusion;
• Any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liraglutide + insulin; Patients will be subjected to a dose escalation of liraglutide up to 1.2 mg, then continue to receive the reached liraglutide dose once daily for 6 months thereafter. Insulin will be continued as routine therapy.	Drug: Liraglutide; Dose escalation of liraglutide starts from 0.6 mg up to 1.2 mg per day.; Drug: Insulin; Receive insulin following clinician's instruction.
Active Comparator: Insulin; Patients will receive insulin injection as a routine therapy.	Drug: Insulin; Receive insulin following clinician's instruction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean amplitude of glycemic excursions (MAGE)	MAGE is measured by applying continuous glucose monitoring system (CGMS) on subjects in each follow-up of this one-year study.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1C		1 year
Change in C-peptide		1 year
Change in insulin dose	hyperglycemic and hypoglycemic events.	1 year
Hyperglycemic and hypoglycemic events	Blood sugar level higher than 11.1 mmol/l or lower than 3.9 mmol/l.	1 year
Life quality evaluation	Number of subjects with disturbance of emotion, sleep, resting or energy.	1 year

Collaborators and Investigators

• Sponsor: Second Xiangya Hospital of Central South University

Publications and helpful links

General Publications

• Rondas D, D'Hertog W, Overbergh L, Mathieu C. Glucagon-like peptide-1: modulator of beta-cell dysfunction and death. Diabetes Obes Metab. 2013 Sep;15 Suppl 3:185-92. doi: 10.1111/dom.12165.
• Chang TJ, Tseng HC, Liu MW, Chang YC, Hsieh ML, Chuang LM. Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation. Sci Rep. 2016 Mar 21;6:23403. doi: 10.1038/srep23403. Erratum In: Sci Rep. 2016 May 31;6:26917.
• Mathieu C, Gillard P. Arresting type 1 diabetes after diagnosis: GAD is not enough. Lancet. 2011 Jul 23;378(9788):291-2. doi: 10.1016/S0140-6736(11)60978-1. Epub 2011 Jun 27. No abstract available.

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: January 2, 2017
• First Submitted That Met QC Criteria: January 3, 2017
• First Posted (Estimate): January 5, 2017

Study Record Updates

• Last Update Posted (Actual): March 18, 2020
• Last Update Submitted That Met QC Criteria: March 17, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: 0002