Liraglutide 3mg (Saxenda) on Weight, Body Composition, Hormonal and Metabolic Parameters in Obese Women With PCOS

Conditions:Ovarian Cancer, Obesity Weight Loss, Women's Studies, Endocrine, Diabetes
Therapuetic Areas:Endocrinology, Oncology, Reproductive
Age Range:18 - 45
Start Date:September 26, 2018
End Date:November 15, 2020
Contact:Karen Elkind-Hirsch, PhD

Use our guide to learn which trials are right for you!

A Randomized Placebo-controlled Double Blind Trial of Liraglutide 3 mg [Saxenda] on Weight, Body Composition, Hormonal and Metabolic Parameters in Obese Women With Polycystic Ovary Syndrome (PCOS)

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.

The drug, liraglutide 3.0 mg was approved for chronic weight management in management in
obese adults with an initial BMI of 30 kg/m2 or greater or in overweight adults BMI of 27
kg/m2 or greater with at least one weight-related co-morbid condition as an adjunct to a
reduced-calorie diet and increased physical activity. Liraglutide is an acylated human
glucagon-like peptide -1 (GLP-1) analog that binds to and activates the GLP-1 receptor. It
lowers body weight through decreased caloric intake while stimulating insulin secretion and
reducing glucagon via a glucose-dependent mechanism. For obesity management, patients may
lose weight with GLP-1 receptor agonists due to other unique actions. Glucagon-like peptide-1
receptor agonists (GLP-1RAs) can slow gastric emptying and increase satiety. While predictors
of weight loss success for the general population are available (protein intake, weight loss
medications), predictors of weight loss success may differ between normal and hyperandrogenic
women. Glucagon-like peptide 1 agonists are linked with dose dependent weight lowering
potential in different obesity related populations. The weight loss effects of GLP-1RAs
previously demonstrated in diabetic and obese non-diabetic patients, offer a unique
opportunity to expand the medical options available to patients with PCOS.

Given this lack of information, the aim of the present study was to investigate the effects
of liraglutide 3mg vs. placebo on body composition as well as hormonal and metabolic features
in non-diabetic obese women with PCOS.The non-diabetic obese female with PCOS offers a unique
model to study the relationship between insulin resistance and adiposity. The investigators
propose a double-blind, placebo-controlled 30-week trial designed to directly examine the
therapeutic effects of liraglutide 3 mg (LIRA 3 mg) compared to placebo on body weight,
hormonal and cardiometabolic parameters in obese non-diabetic women with PCOS. All patients
will receive diet and lifestyle counseling, including advice on exercise commencing during
the lead-in period and continuing throughout the study. In this study, the investigators will
examine the efficacy of LIRA 3mg on body weight and body composition, reproductive function
metabolic parameters and cardiovascular risk factors in a well-defined group of
pre-menopausal obese non-diabetic women with hyperandrogenism, focusing on the relationship
to obesity and insulin resistance.

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

- 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

- 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
We found this trial at
Baton Rouge, Louisiana 70815
Principal Investigator: Karen Elkind-Hirsch, Ph.D.
Phone: 225-231-5278
Baton Rouge, LA
Click here to add this to my saved trials