Gut Microbiome Changes Following Liraglutide Treatment in Obese Subjects or Overweight Subjects With Co-morbidities

Inclusion Criteria:

• Informed consent obtained before any trial-related activity takes place

• Obesity (BMI ≥30.0 kg/m2); or overweight (BMI ≥27.0 kg/m2) with treated or untreatedco-morbid dyslipidemia (Low-density lipoprotein ≥3.38mmol/l (130 mg/dl), ortriglycerides ≥1.7mmol/l (150 mg/dl), or high-density lipoprotein <1.04mmol/l (40mg/dl) for males and <1.30mmol/l (50 mg/dl) for females) and/or hypertension (Systolicblood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg)

• Age ≥18 years, ≤75 years

Exclusion Criteria:

• Diagnosis of type 1 or type 2 diabetes per the judgment of the investigator

• HbA1c ≥6.5% or fasting plasma glucose ≥7.0 mmol/l or 2-hour post-challenge plasmaglucose ≥11.1 mmol/liter (at screening)

• less than 5 kg self-reported change during the previous 3 months

• Previous treatment with GLP-1 receptor agonists (including liraglutide or exenatide)within the last 3 months

• Known or suspected hypersensitivity to trial product, related products or other GLP-1receptor agonist

• Diet attempts using herbal supplements or over-the-counter medications within 1 monthsbefore screening, or use prescription drugs for weight loss within 3 months beforescreening (for example: orlistat, fenfluramine, maindole ) Or lipid dissolvinginjection (for example: lipolysis needle) treatment

• Current or history of treatment with medications that may cause significant weightgain, within 3 months prior to screening, including systemic corticosteroids (morethan 1 week),tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g. imipramine, amitriptiline, mirtazapin, paroxetine, phenelzine, clorpromazine,thioridazine, clozapine, lanzapine, valproic acid and its derivatives, and lithium)

• A history of malignant tumors within 5 years before screening (except for fullytreated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localprostate cancer after radical resection, and ductal carcinoma in situ after radicaloperation)

• A history of severe heart disease is defined as: decompensated heart insufficiency (NYHA III-IV), and/or a history of unstable angina within 6 months before screening,and a history of myocardial infarction within 12 months

• Obesity induced by other endocrinologic disorders (e.g. Cushing's Syndrome)

• Suffer from gastrointestinal motility disorders or obstruction diseases, such asgastroparesis, gastroesophageal reflux disease

• Any lifetime history of a suicidal attempt or A history of any suicidal behavior inthe last month prior to randomization

• A patient health questionnaire (PHQ-9) score of ≥15

• Montreal Cognitive Assessment Scale (MoCA) score <26 at screening;

• Any suicidal ideation of type 4 or 5 on the Columbian Suicidality Severity RatingScale (C-SSRS) in the last month prior to randomization

• Untreated or uncontrolled hypothyroidism/hyperthyroidism defined asthyroid-stimulating hormone >6 mIU/liter or <0.4 mIU/liter

• Screening calcitonin ≥50 ng/liter

• Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familialmedullary thyroid carcinoma (FMTC) or Personal history of non-familial medullarythyroid carcinoma

• History of chronic pancreatitis or idiopathic acute pancreatitis or amylase ≥ 3 timesthe upper limit of normal value during screening

• ALT or AST or TBiL>3 times the upper limit of normal value during screening

• Impaired renal function, defined as serum creatinine level ≥1.5mg/dL (132µmol/L) inmen or ≥1.4mg/dL (123µmol/L) in women at screening

• Untreated or uncontrolled severe dyslipidemia, defined as blood LDL-C≥190mg/dl (4.94mmol/L) and/or TG≥500mg/dl (5.65mmol/L) at screening

• Uncontrolled treated/untreated hypertension (systolic blood pressure ≥160 mm Hg and/ordiastolic blood pressure ≥100 mm Hg)

• Previous surgical treatment for obesity (excluding liposuction if performed >1 yearbefore trial entry)

• According to the investigator's judgment, those who have a surgical plan during thetrial period (except for minor operations)

• Participated in any weight loss clinical trials within 3 months before screening, andtook any experimental drugs within 1 month (Re-screening is allowed once within thelimit of the recruitment period)

• Known or suspected abuse of alcohol or narcotics within 6 months

• Poor compliance with restrictions on diet and behavior during screening

• Females of child-bearing potential who are pregnant, breast-feeding

• Participants intend to become pregnant or are not using adequate contraceptive methodsor subjects who use hormonal contraceptives

• The investigator considers that it is not suitable for participants (for example, theinvestigator judges that severe obstructive sleep apnea will cause gastroesophagealreflux).