The Effect and the Pharmacogenomics Study of Liraglutide in Obese Patients

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.

Study Overview

• Status: Withdrawn
• Conditions: Obesity
• Intervention / Treatment: Drug: Liraglutide; Drug: Liraglutide;metformin

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients aged 18 to 65 years (to the date of screening)；
2. 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).
3. 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.
4. Weight stable for more than 3 months (weight fluctuations <5%).

Exclusion Criteria:

1. Pregnant female.
2. 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.
3. Severe cardiovascular and cerebrovascular diseases (heart failure, myocardial infarction, acute hemorrhagic or ischemic encephalopathy), pulmonary heart disease or pulmonary insufficiency, renal failure, severe hepatitis.
4. Combined with acute complications of diabetes such as ketoacidosis, lactic acidosis, hyperosmolar state of diabetes.
5. Nearly a month had surgery, trauma, infection and so on.
6. Limb deformity incomplete, difficult to accurately determine the height, weight and other physical indicators.
7. Poor medication compliance or serious side effects (severe rash, syncope, etc.).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liraglutide; Obese patients with HbA1C lower than 9.0%,receive Liraglutide alone for 3 months.	Drug: Liraglutide; 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.; Other Names: Victoza
Experimental: Liraglutide combined with metformin; Obese patients with HbA1C ≥9.0%, receive Liraglutide in combination with metformin for 3 months.	Drug: Liraglutide;metformin; 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.; Other Names: Victoza;Glucophage

What is the study measuring?

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
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
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

Collaborators and Investigators

• Sponsor: Xiangya Hospital of Central South University

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: March 27, 2018
• First Submitted That Met QC Criteria: April 8, 2021
• First Posted (Actual): April 9, 2021

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide; Metformin
• Other Study ID Numbers: 201710832

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No