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

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

Detailed Description
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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.

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

Conditions
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Type 1 Diabetes Mellitus, Autoimmune Diabetes

Intervention / Treatment
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* Drug: Liraglutide
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide + insulin<br>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<br>* Dose escalation of liraglutide starts from 0.6 mg up to 1.2 mg per day.<br>Drug: Insulin<br>* Receive insulin following clinician's instruction.<br>|
| Active Comparator: Insulin<br>Patients will receive insulin injection as a routine therapy. | Drug: Insulin<br>* Receive insulin following clinician's instruction.<br>|

What is the study measuring?
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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 |