Liraglutide 3mg (Saxenda) on Weight, Body Composition, Hormonal and Metabolic Parameters in Obese Women With PCOS
Condition: Pre Diabetes; Polycystic Ovary Syndrome; Obesity Android
MeSH terms: Polycystic Ovary Syndrome; Prediabetic State; Syndrome; Body Weight
Intervention: Liraglutide Pen Injector [Saxenda]; Placebo Liraglutide Pen Injector
Intervention description: daily sc injection of liraglutide with final dose of 3mg daily; daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo
Intervention MeSH terms: Liraglutide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Double- Blind 2:1 Drug: Placebo
Enrollment: 88.0
Sex: Female
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: prediabetes; PCOS; GLP-1 agonist; weight loss

Summary:

      There is a growing need to develop pharmacologic interventions to improve metabolic function
      in women with polycystic ovary syndrome (PCOS). Given that PCOS is a frequent condition and
      weight loss is essential but difficult to achieve, it is important to study if the effect on
      body weight reported in other studies can be confirmed in a selected population of
      hyperandrogenic patients, especially with medications currently approved for weight
      reduction. High dose liraglutide alone results in significant weight reduction in obese women
      without PCOS. There is limited data on weight loss with high dose liraglutide in non-diabetic
      females with PCOS treated with this agent . Studies on the effect of anti-obesity medication
      combined with lifestyle changes on body weight and composition and androgen excess in obese
      women diagnosed with PCOS are lacking. The investigators aim to elucidate the most
      efficacious weight reduction regime in obese PCOS women. The investigators further hope to
      determine which treatment(s) addressing the multifaceted disturbances of this disorder in
      patients with PCOS and obesity emerges as the preferable therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female gender

          -  18-45 years of age

          -  BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with one or more obesity-associated co-morbid
             conditions (e.g. hypertension, and dyslipidemia)

          -  PCOS- NIH criteria hyperandrogenism and irregular menstrual cyclicity

          -  Non-diabetic as determined by a 75 gram oral glucose tolerance test (OGTT) and
             hemoglobin A1C. Non-diabetic is inclusive of women with impaired fasting glucose
             (IFG), impaired glucose tolerance (IGT), or both (IFG/IGT). Participants with diabetes
             will be excluded

          -  Willing to use effective contraception consistently during therapy which is defined
             as:

               -  an intrauterine device, tubal sterilization, or male partner vasectomy, or

               -  combination of two barrier methods with one being male condom.

          -  Written consent for participation in the study

        Exclusion Criteria:

          -  Presence of significant systemic disease, cerebrovascular disease, clinically
             significant cardiac abnormalities or heart problems including congestive heart
             failure, unstable angina or acute myocardial infarction, current infectious liver
             disease, acute stroke or transient ischemic attacks, history of pancreatitis, or
             diabetes mellitus (Type 1 or 2)

          -  Any hepatic diseases in the past (infectious liver disease, viral hepatitis, toxic
             hepatic damage, jaundice of unknown etiology) or severe hepatic insufficiency and/or
             significant abnormal liver function tests defined as aspartate aminotransferase (AST)
             >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN

          -  Renal impairment (e.g., serum creatinine levels ≥1.4 mg/dL for women, or eGFR <60
             mL/min/1.73 m2) or history of unstable or rapidly progressing renal disease or end
             stage renal disease.

          -  Uncontrolled thyroid disease (documented normal TSH), Cushing's syndrome, congenital
             adrenal hyperplasia or clinically significant elevations in prolactin levels. The
             clinical significance of prolactin levels will be determined by the treating physician

          -  Significantly elevated triglyceride levels (fasting triglyceride > 400 mg %)

          -  Untreated or poorly controlled hypertension (sitting blood pressure > 160/95 mm Hg)

          -  Use of hormonal medications, the use of medications that cause clinically significant
             weight gain or loss (prescription or OTC) and medications known to exacerbate glucose
             tolerance (such as isotretinoin, hormonal contraceptives, GnRH analogues,
             glucocorticoids, anabolic steroids, C-19 progestins) including herbal medicines for at
             least 8 weeks. Use of anti-androgens that act peripherally to reduce hirsutism such as
             5-alpha reductase inhibitors (finasteride, spironolactone, flutamide) for at least 4
             weeks

          -  Prior history of a malignant disease requiring chemotherapy

          -  Family or personal history of familial medullary thyroid carcinoma or multiple
             endocrine neoplasia type 2

          -  Known hypersensitivity or contraindications to use GLP1 receptor agonists

          -  Use of metformin, thiazolidinediones, GLP-1 receptor agonists, dipeptidyl peptidase-4
             (DPP-4) inhibitors, sodium/glucose co-transporter 2 (SGLT2) inhibitors or weight loss
             medications (prescription or OTC) stopped for at least 4 weeks

          -  Prior use of medication to treat diabetes except gestational diabetes

          -  Eating disorders (anorexia, bulimia) or gastrointestinal disorders

          -  Suspected pregnancy (documented negative serum pregnancy test), desiring pregnancy in
             next 15 months, breastfeeding, or known pregnancy in last three months

          -  Active or prior history of substance abuse (smoke or tobacco use within past 6 months)
             or significant intake of alcohol

          -  Previous bariatric surgery or device intervention for obesity

          -  Patient not willing to use barrier contraception during study period (unless
             sterilized or have an IUD)

          -  History of major depressive or other severe psychiatric disorders

          -  Inability or refusal to comply with protocol

          -  Currently participating or having participated in an experimental drug study in
             previous three months