Efficacy and Safety of Liraglutide on Body Weight in Obese Subjects or Overweight Subjects With Co-morbidities

Last updated: July 24, 2020
Sponsor: Xiangya Hospital of Central South University
Overall Status: Active - Recruiting

Phase

3

Condition

Obesity

Diabetes Prevention

Hypertriglyceridemia

Treatment

N/A

Clinical Study ID

NCT04487743
202006108
HDSJ19LLLT
  • Ages 18-75
  • All Genders

Study Summary

We performed a multicenter, randomized, double-blind, placebo-controlled 28-week trial. 300 non-diabetic obese subjects or overweight subjects with co-morbidities were randomly assigned. Eligible participants were randomized 2:1 to once-daily subcutaneous injections of either liraglutide or placebo. The primary outcome is to investigate the safety, tolerability from baseline to end of treatment.

Eligibility Criteria

Inclusion

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

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).

Study Design

Total Participants: 300
Study Start date:
May 09, 2020
Estimated Completion Date:
June 30, 2022

Study Description

We performed a multicenter, randomized, double-blind, placebo-controlled 28-week trial. 300 individuals (18-75 years of age, body-mass index ≥30 kg/m2 or BMI 27-30kg/m2 accompanied by at least one weight-related complication (treated or untreated hypertension, dyslipidemia, pre-diabetes)) were randomly assigned. All the patients provided written informed consent before participation. Key exclusion criteria were type 1 or 2 diabetes, the use of medications that cause clinically significant weight gain or loss, previous bariatric surgery, a history of pancreatitis, a history of major depressive or other severe psychiatric disorders, and a family or personal history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma. Eligible participants were randomized 2:1 to once-daily subcutaneous injections of either liraglutide or placebo using a computer-generated, centrally administered procedure. Patients, investigators, and the sponsor were unaware of the study-group assignments. The primary endpoint was change in bodyweight during the 28 weeks of the study in the intention-to-treat population. The proportion of people losing more than 5% of baseline weight was also assessed. Secondary efficacy endpoints included the proportion of people losing more than 10% of baseline weight was also assessed, change in waist circumference, hip circumference, WHR, systolic and diastolic blood pressure, fasting lipids (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), glucose metabolism parameters (fasting plasma glucose, 2-hour post-challenge plasma glucose and glycosylated haemoglobin [HbA1c]).

Connect with a study center

  • Xiangya Hospital of Central South University

    Changsha, Hunan 410008
    China

    Active - Recruiting

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