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

NCT03480022 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: U1111-1198-4126
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Pre Diabetes; Polycystic Ovary Syndrome; Obesity Android

Keywords

prediabetes; PCOS; GLP-1 agonist; weight loss

Outcome Measures

Primary Outcomes (2)

• Absolute Body Weight (BW)

  Treatment impact on change in body weight after 32 weeks of treatment.

  32 weeks of treatment

• Free Androgen Index (FAI)

  Drug treatment effect on free androgen levels as calculated as FAI= total testosterone (T) concentrations divided by sex hormone binding globulin (SHBG) levels. A higher score indicates a worse outcome (more androgenic).

  32 weeks of treatment

Secondary Outcomes (27)

• Body Mass Index (BMI)

  32 weeks of treatment

• Change in Percent Body Weight

  Change from baseline (time 0) to study end (32 weeks)

• 5% Weight Loss From Baseline

  32 weeks of treatment

• 10% Body Weight Loss From Baseline

  32 weeks of treatment

• Abdominal Adiposity (Waist Circumference [WC]

  32 weeks of treatment

Study Arms (2)

Liraglutide Pen Injector (Saxenda)

EXPERIMENTAL

Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg liraglutide SQ daily

Drug: Liraglutide Pen Injector [Saxenda]

Placebo liraglutide pen injector

PLACEBO COMPARATOR

Start injection of placebo liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), step up to 1.2 mg SC QD for 1week, to 1.8 mg SC QD for 1 week, 2.4 mg SC QD for 1week, to a final dose of 3.0 mg placebo liraglutide SQ daily

Drug: Placebo Liraglutide Pen Injector

Interventions

Liraglutide Pen Injector [Saxenda] DRUG

daily sc injection of liraglutide with final dose of 3mg daily

Also known as: Liraglutide 3mg, Saxenda

Liraglutide Pen Injector (Saxenda)

Placebo Liraglutide Pen Injector DRUG

daily sc injection of placebo liraglutide with final dose of 3mg daily of placebo

Also known as: Placebo Saxenda, Placebo liraglutide 3 mg

Placebo liraglutide pen injector

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Patients must be female to have the disorder being studied since it involved the female reproductive system
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female gender
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Woman's: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Woman's Hospital

Baton Rouge, Louisiana, 70817, United States

Location

Related Publications (1)

• Elkind-Hirsch KE, Chappell N, Shaler D, Storment J, Bellanger D. Liraglutide 3 mg on weight, body composition, and hormonal and metabolic parameters in women with obesity and polycystic ovary syndrome: a randomized placebo-controlled-phase 3 study. Fertil Steril. 2022 Aug;118(2):371-381. doi: 10.1016/j.fertnstert.2022.04.027. Epub 2022 Jun 13.

  PMID: 35710599 DERIVED

MeSH Terms

Conditions

Glucose Intolerance; Polycystic Ovary Syndrome; Obesity, Abdominal; Prediabetic State; Weight Loss

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Body Weight Changes

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Director of Research
• Organization: Woman's Hospital

karen.elkind-hirsch@womans.org

12252315278

Study Officials

• Peggy Dean, PharmD

  Woman's Hospital Foundation IRB

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double- Blind 2:1 Drug: Placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Scientific Director of Research

Study Record Dates

• First Submitted: March 13, 2018
• First Posted: March 27, 2018
• Study Start: September 26, 2018
• Primary Completion: February 22, 2021
• Study Completion: May 19, 2021
• Last Updated: June 7, 2021
• Results First Posted: June 7, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)