The Effect and the Pharmacogenomics Study of Liraglutide in Obese Patients

Study Overview
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Brief Summary
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This studay evaluates the effect of liraglutide in the treatment of obese patients ande the influence of genetic factors on the curative effect.Half of participants will receive Liraglutide alone,while the other half who can not achieving adequate glycaemic control will receive Liraglutide and metformin in combination.

Detailed Description
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Background:The rapid growth of obese or overweight people in the world has become a major social problem. Obese often associated with kinds of metabolic disorders, especially type 2 diabetes, and Liraglutide can effectively reduce weight and improve blood glucose.Previous studies have indicated that most patients will experience different degrees of weight loss after using Liraglutide, but there is also a small number of patients with no significant weight loss.The gene polymorphism among individuals may affect the weight loss effect of Liraglutide. Objectives：1.To find the relationships between genetic variants and the response of Liraglutide to treatment of obese patients.2.To investigate the effects of Liraglutide on weight, metabolism (blood glucose, blood lipid, uric acid, etc.) and gut microbiota in obese Chinese patients. Intervention:Half of participants will receive Liraglutide alone,while the other half who can not achieving adequate glycaemic control will receive Liraglutide and metformin in combination.

Official Title
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The Effect and the Pharmacogenomics Study of Liraglutide in Obese Patients

Conditions
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Obesity

Intervention / Treatment
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* Drug: Liraglutide
* Drug: Liraglutide;metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 18 to 65 years (to the date of screening)； The newly diagnosed obese patients (BMI greater than 28 kg/m2) or abdominal obesity (male waist circumference is greater than 90cm, female waist is greater than 85cm). Nearly a month have not used weight-related drugs,including various weight-loss drugs,GLP-1 analogs or agonists,metformin, acarbose,insulin,anti hyperthyroid drugs,etc;Or recently used weight-related drugs but the stable dose was more than 1 month,and the drug dose remained constant or decreased during the trial. Weight stable for more than 3 months (weight fluctuations <5%). Exclusion Criteria: Pregnant female. Secondary diseases caused by other diseases: including hypothyroidism, increased cortisol, hypothalamic and pituitary lesions caused by obesity, all kinds of drug-induced obesity, and others. Severe cardiovascular and cerebrovascular diseases (heart failure, myocardial infarction, acute hemorrhagic or ischemic encephalopathy), pulmonary heart disease or pulmonary insufficiency, renal failure, severe hepatitis. Combined with acute complications of diabetes such as ketoacidosis, lactic acidosis, hyperosmolar state of diabetes. Nearly a month had surgery, trauma, infection and so on. Limb deformity incomplete, difficult to accurately determine the height, weight and other physical indicators. Poor medication compliance or serious side effects (severe rash, syncope, etc.).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide<br>Obese patients with HbA1C lower than 9.0%,receive Liraglutide alone for 3 months. | Drug: Liraglutide<br>* The treatment of Liraglutide lasted three months,During the first week: 0.6mg per day, subcutaneous injection;During the second week: 1.2mg per day, subcutaneous injection; From third week onwards,1.8mg per day, subcutaneous injection.<br>* Other names: Victoza;|
| Experimental: Liraglutide combined with metformin<br>Obese patients with HbA1C ≥9.0%, receive Liraglutide in combination with metformin for 3 months. | Drug: Liraglutide;metformin<br>* The treatment of Liraglutide combined with metformin lasted three months.For Liraglutide,during the first week: 0.6mg per day, subcutaneous injection;during the second week: 1.2mg per day, subcutaneous injection; from third week onwards,1.8mg per day, subcutaneous injection.For metformin,during three months:0.5g each time, 3 times per day,oral.<br>* Other names: Victoza;Glucophage;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight Change at 3 months | Measured in kilograms | baseline and 3 months | 
| Genotype |  | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in waist circumference | Measured in cm | baseline and 3 months | 
| Change in systolic blood pressure | Measured in mmHg | baseline and 3 months | 
| Change in diastolic blood pressure | Measured in mmHg | baseline and 3 months | 
| Change in HbA1c | Measured in % | baseline and 3 months | 
| Change in plasma glucose | Measured in mmol/l | baseline and 3 months | 
| Change in insulin | Measured in μU/ml | baseline and 3 months | 
| Change in lipids-total cholesterol | Measured in mmol/l | baseline and 3 months | 
| Change in lipids-low density lipoprotein cholesterol | Measured in mmol/l | baseline and 3 months | 
| Change in lipids-high density lipoprotein cholesterol | Measured in mmol/l | baseline and 3 months | 
| Change in lipids-triglycerides | Measured in mmol/l | baseline and 3 months | 
| Change in lipids-free fatty acids | Measured in μmol/l | baseline and 3 months | 
| Change in Uric Acid | Measured in mmol/l | baseline and 3 months | 
| Gut microbiota composition | Gut microbiota composition is assessed by 16S rRNA pyrosequencing. This analysis allows to obtain the relative abundance (%) of the different bacterial taxa and OTUs (operational taxonomic units). | 3 months |