The purpose of the trial is to assess whether the beneficial effect of liraglutide on weight is mediated by changes in the composition of the intestinal Microbiome. The main mechanisms of action of liraglutide were traced to a reduction in the secretion of glucagon and slowing gastric emptying resulting in decreased appetite and body weight. It also seems that liraglutide is capable of increasing the satiety signals thanks to a dual mechanism of stimulation and inhibition induced by medication. Pomc neurons (opiomelacortin) present in hypothalamic arcuate nuclei, stimulated by liraglutide, glucagon-like peptide- 1 (GLP-1) receptor expressed by inhibiting intensely appetite. At the same time through the GABAergic neuronal activity is inhibited neuropeptide Y(NPY) deputies to the production of orexins that are powerful promoters of appetite. Alterations in the composition of the human gut microbiome occur in metabolic disorders such as obesity, diabetes. Liraglutide has been reported to switch microbiome composition towards lean-related bacterial phylotypes in animal studies. This leads to hypothesize that the switch of microbiome by liraglutide may be one of the mechanisms through which liraglutide may exert its effect. In particular the investigators hypothesize that liraglutide could restore a healthy microbiome or at least improve the microbiome composition through slowing gastrointestinal motility. Moreover, the liraglutide-related change of microbiome could be an additional mechanism that contribute to the beneficial metabolic effect of liraglutide. To test this hypothesis the investigators will investigate if there will be any change of gut microbiome assessed as Firmicutes-to-Bacteroidetes ratio after liraglutide treatment. In order to understand if the change of gut microbiome after liraglutide treatment occurs as an association or contributes to the effect of liraglutide ,the investigators will correlate the Firmicutes-to-Bacteroidetes ratios with the changes of Body Mass Index, Body Composition, appetite parameters, chronic inflammation parameters, lipid profile and insulin resistance. All the subjects will follow the same diet in order to avoid any bias.

This is a randomized, double-blind, parallel group, placebo-controlled trial comparing liraglutide 3.0 mg with placebo both administered subcutaneously once-daily in subjects with established obesity. Subjects will be randomised in a 1:1 ratio to receive either liraglutide 3.0 mg or placebo as an adjunct to standard-of-care.All baseline assessments will be done prior to administration of the first dose of trial product while all the follow up assessments will be done at the end of the trial. Dose escalation of liraglutide/placebo will take place during the first 4 weeks after randomisation as described. All subjects will aim at reaching the recommended target dose of 3.0 mg liraglutide once-daily or the corresponding volume of placebo. In this trial approximately 70 subjects will be randomly assigned to trial product.

Inclusion Criteria:

1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial;
2. Age ≥ 18 years and < 65 years at the time of signing informed consent;
3. Body mass index (BMI) ≥ 30 kg/m2
4. Stable body weight during the previous 3 months (< 5 kg self-reported weight change).

Exclusion Criteria:

General Safety

1. Current or history of treatment with medications that may cause significant weight gain for at least 3 months before this trial;

2. Current use or use within three months before this trial of GLP-1 receptor agonist, pramlintide, sibutramine, orlistat, zonisamide, topiramate or phentermine;

3. Type 1 diabetes;

4. Type 2 diabetes;

5. Obesity related to endocrine diseases;

6. Hepatic Failure (AST and/or ALT >3 times upper limit of normal and/or Total Bilirubin >1.7 upper limit of normal)

7. End stage renal disease (eGFR < 30 ml/min/1.73 m2 ) or chronic or intermittent haemodialysis or peritoneal dialysis

8. History or presence of chronic pancreatitis

9. Presence of acute pancreatitis within the past 180 days prior to the day of screening

10. Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma

11. Presence or history of malignant neoplasms within the past 5 years prior to the day of screening

12. Severe psychiatric disorder which in the investigator's opinion could compromise compliance with the protocol

13. Known or suspected hypersensitivity to trial product(s) or related products

14. Previous participation in this trial. Participation is defined as randomisation

15. Receipt of any investigational medicinal product within 30 days before screening

16. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method i.e.:

    • patients who use combined hormonal contraceptives (containing estreogen and progesterone) associated with inhibition of ovulation or oral, intravaginal that transdermal;
    • patients who use hormonal contraceptives based only progesterone that inhibit ovulation, whether oral, injectable or implantable
    • patients with placement of IUD (intrauterine device)
    • patients with positioning of hormone releasing intrauterine systems
    • patients with bilateral tubal occlusion
    • patients with vasectomized partner
    • patients who practice sexual abstinence

17. Any disorder, unwillingness or inability, which in the investigator's opinion, might jeopardise the subject's safety or compliance with the protocol

18. Previous surgical treatment for obesity (excluding liposuction >1 year before trial entry); 19 ) Inflammatory bowel diseases; 20 ) recent antibiotic therapy ( within 30 days before screening)

Cardiovascular- related

• Any of the following: myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening
• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening;
• Presently classified as being in New York Heart Association (NYHA) Class IV heart failure