Effect of rimonabant and metformin on glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 in obese women with polycystic ovary syndrome

Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Metabolic consequences associated with PCOS include, but are not limited to, insulin resistance (IR), type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). This narrative review aims to provide a comprehensive overview of the potential therapeutic roles of the incretin-based therapies in the management of PCOS. Methods: We performed a systematic search of databases including PubMed, MEDLINE and EMBASE up to 1 October 2020. We developed a search string of medical subject headings (MeSH) including the terms PCOS, incretin mimetics, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-1 receptor antagonists (GLP-1 RAs), liraglutide, exenatide, semaglutide, dipeptidyl peptidase-4 (DPP-4) inhibitors, combined with IR, testosterone and sex hormone-binding globulin (SHBG). Results: We identified 854 relevant articles and, after the initial screening, eight interventional animal studies, one observational animal study, 14 interventional human studies, two case–control studies and one systematic review were included. These studies showed the potential significant roles of GLP-1 RAs and DPP-4 inhibitors in the management of PCOS, with significant improvements in the metabolic parameters, including substantial weight reduction and improved insulin sensitivity. These agents also improved the hormonal parameters through decreased free androgen and increased SHBG. Moreover, they improved menstrual regularity, increased fertility with enhanced ovulation and pregnancy in obese women with PCOS. Conclusion: GLP-1 RAs and DPP-4 inhibitors have a promising therapeutic role in PCOS; however, larger clinical trials are needed to establish the role of incretin-based therapies in the management of PCOS.

Download Full-text

Overview of the Role of Glucagon like Peptide-1 Receptor Agonists in the Management of Polycystic Ovary Syndrome

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i58b34206 ◽

2021 ◽

pp. 312-318

Author(s):

Asma Alshenqiti ◽

Ghaida Almohammadi

Keyword(s):

Insulin Resistance ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Premenopausal Women ◽

Ovary Syndrome ◽

Receptor Agonists ◽

Long Term Effect ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects premenopausal women. It is a multifactorial disease that involves hyperandrogenism, ovulatory dysfunction, insulin resistance and genetic factors. Women with PCOS present with menstrual disorder, hirsutism, and obesity. Diagnosis of PCOS involves evidence of ovulation dysfunction, hyperandrogenism, either physical or biochemical, and ultrasonographic evaluation of the ovarian morphology. There is no single treatment for PCOS but rather it is a symptom-oriented management. Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) are insulin sensitizers usually involved in the management of PCOS. Aim: This article aims to review the evidence regarding the role GLP-1 RAs in the management of polycystic ovary syndrome. Conclusion: GLP-1 RAs found to improve PCOS outcomes in the form of increasing menstrual frequency, reducing androgens levels, higher pregnancy rates, weight reduction, and improving insulin resistance. Mild and transient adverse events were observed such as nausea, diarrhea, headache, insomnia and mild hypoglycemic events. However, long term studies are required to assess long term effect of GLP-1 RAs and its safety during pregnancy.

Download Full-text

An impaired glucagon-like peptide-1 response is associated with prediabetes in polycystic ovary syndrome with obesity

Journal of International Medical Research ◽

10.1177/0300060519865351 ◽

2019 ◽

Vol 47 (10) ◽

pp. 4691-4700 ◽

Cited By ~ 1

Author(s):

Simona Ferjan ◽

Mojca Jensterle ◽

Tjasa Oblak ◽

Irena Prodan Zitnik ◽

Janja Marc ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Glucose Tolerance ◽

Cell Function ◽

Polycystic Ovary ◽

Tolerance Test ◽

Normal Glucose Tolerance ◽

Oral Glucose ◽

Ovary Syndrome ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Objective Impaired glucose homeostasis in polycystic ovary syndrome (PCOS) is associated with obesity, age, and disease phenotype. This study aimed to investigate the glucagon-like peptide-1 (GLP-1) response in patients with obesity and PCOS with normal glucose tolerance (NGT) or prediabetes. Methods Twenty-six women with obesity and PCOS were included. Thirteen women had NGT and 13 had prediabetes. Serum glucose, insulin, and GLP-1 levels were measured during an oral glucose tolerance test. Beta-cell function and insulin resistance were determined. Results Women with prediabetes had significantly lower GLP-1 levels than did those with NGT after a glucose load. GLP-1 levels <3.02 pM at 120 minutes were associated with prediabetes. Women with prediabetes had a lower oral glucose insulin sensitivity (OGIS) index and greater amount of visceral adipose tissue than did those with NGT. Plasma GLP-1 levels at 120 minutes were correlated with visceral adiposity and the OGIS index. A change in GLP-1 levels was correlated with a family history of type 2 diabetes. Conclusion The GLP-1 response is lower in patients with obesity, PCOS, and prediabetes than in those with obesity, PCOS, and NGT. Further investigation of the GLP-1 response as a potential separate risk factor for prediabetes in PCOS is required.

Download Full-text