Dataset Information

Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.

ABSTRACT: OBJECTIVE:The effect of metformin on weight reduction in polycystic ovary syndrome (PCOS) is often unsatisfactory. In this study, we investigated the potential add-on effect of treatment with the glucagon-like peptide-1 receptor agonist liraglutide on weight loss in obese nondiabetic women with PCOS who had lost <5% body weight during pretreatment with metformin. METHODS:A total of 40 obese women with PCOS, who had been pretreated with metformin for at least 6 months, participated in a 12-week open-label, prospective study. They were randomized to one of three treatment arms: metformin (MET) arm 1000 mg BID, liraglutide (LIRA) arm 1.2 mg QD s.c., or combined MET 1000 mg BID and LIRA (COMBI) 1.2 mg QD s.c. Lifestyle intervention was not actively promoted. The primary outcome was change in body weight. RESULTS:Thirty six patients (aged 31.3 ± 7.1 years, BMI 37.1 ± 4.6 kg/m²) completed the study: 14 on MET, 11 on LIRA, and 11 on combined treatment. COMBI therapy was superior to LIRA and MET monotherapy in reducing weight, BMI, and waist circumference. Subjects treated with COMBI lost on average 6.5 ± 2.8 kg compared with a 3.8 ± 3.7 kg loss in the LIRA group and a 1.2 ± 1.4 kg loss in the MET group (P<0.001). The extent of weight loss was stratified: a total of 38% of subjects were high responders who lost ?5% body weight, 22% of them in the COMBI arm compared with 16 and 0% in the LIRA and MET arm respectively. BMI decreased by 2.4 ± 1.0 in the COMBI arm compared with 1.3 ± 1.3 in LIRA and 0.5 ± 0.5 in the MET arm (P<0.001). Waist circumference also decreased by 5.5 ± 3.8 cm in the COMBI arm compared with 3.2 ± 2.9 cm in LIRA and 1.6 ± 2.9 cm in the MET arm (P=0.029). Subjects treated with liraglutide experienced more nausea than those treated with metformin, but severity of nausea decreased over time and did not correlate with weight loss. CONCLUSIONS:Short-term combined treatment with liraglutide and metformin was associated with significant weight loss and decrease in waist circumference in obese women with PCOS who had previously been poor responders regarding weight reduction on metformin monotherapy.

SUBMITTER: Jensterle Sever M

PROVIDER: S-EPMC3922503 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.

Jensterle Sever Mojca M Kocjan Tomaz T Pfeifer Marija M Kravos Nika Aleksandra NA Janez Andrej A

European journal of endocrinology 20140207 3

<h4>Objective</h4>The effect of metformin on weight reduction in polycystic ovary syndrome (PCOS) is often unsatisfactory. In this study, we investigated the potential add-on effect of treatment with the glucagon-like peptide-1 receptor agonist liraglutide on weight loss in obese nondiabetic women with PCOS who had lost <5% body weight during pretreatment with metformin.<h4>Methods</h4>A total of 40 obese women with PCOS, who had been pretreated with metformin for at least 6 months, participated ...[more]

PMID: 24362411

Similar Datasets

Project description:BackgroundObesity and insulin resistance (IR) are common features of polycystic ovary syndrome (PCOS). Metformin (MET) increases insulin sensitivity, but it is associated with unsatisfactory weight loss. The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes. This study aimed to explore the therapeutic effects of exenatide once-weekly (QW) combined with MET on body weight, as well as metabolic and endocrinological parameters in overweight/obese women with PCOS.MethodsFifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups: MET (500 mg three times a day [TID]) or combination treatment (COM) (MET 500 mg TID, exenatide 2 mg QW) for 12 weeks. The primary outcomes were anthropometric changes associated with obesity, and the secondary outcomes included changes in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein.ResultsForty (80%) patients completed the study. COM therapy was superior to MET monotherapy in reducing weight (P = 0.045), body mass index (BMI) (P = 0.041), and waist circumference (P = 0.023). Patients in the COM group on an average lost 3.8 ± 2.4 kg compared with 2.1 ± 3.0 kg in the MET group. In the COM group, BMI and waist circumference decreased by 1.4 ± 0.87 kg/m2 and 4.63 ± 4.42 cm compared with 0.77 ± 1.17 kg/m2 and 1.72 ± 3.07 cm in the MET group, respectively. Moreover, levels of fasting glucose, oral glucose tolerance test (OGTT) 2-h glucose, and OGTT 2-h insulin were significantly lower with COM therapy than with MET (P < 0.050). Mild and moderate gastrointestinal reactions were the most common adverse events in both groups.ConclusionsCOM therapy was more effective than MET alone in reducing body weight, BMI, and waist circumference, and improving insulin sensitivity in overweight/obese women with PCOS, with acceptable short-term side effects.Trial registrationClinicalTrials.gov, NCT04029272. https://clinicaltrials.gov/ct2/show/NCT04029272.

Project description:BackgroundAt present, a number of clinical trials have been carried out on GLP-1 receptor agonist liraglutide in the treatment of polycystic ovary syndrome (PCOS). However, the effect of liraglutide on follicle development and its specific mechanism are still unclear.MethodsRNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation.ResultsIn the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation.ConclusionsThe present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS.Trial registrationNot applicable.

Project description:Background: Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder with heterogeneous manifestations and complex etiology. As a leading cause of anovulatory infertility, the molecular diversity of the follicular microenvironment has not been fully elucidated. The aim of the present study was to investigate the follicular fluid proteomic profiles of overweight/obese and normal-weight women with PCOS, to identify novel molecular mechanisms underlying PCOS and to determine the effect of obesity on the follicular fluid protein profiles. Methods: Follicular fluid samples were collected from 3 different groups: overweight/obese PCOS patients (n = 29), normal-weight PCOS patients (n = 29), and normo-ovulatory controls (n = 29). We used a quantitative approach with tandem mass tag labeling and liquid chromatography tandem mass spectrometry to identify the differentially expressed proteins. Differential abundance of four selected proteins was confirmed by ELISA. Gene Set Enrichment Analysis was also conducted to further explore our findings. Furthermore, we compared the clinical, hormonal, and biochemical characteristics of overweight/obese and normal-weight patients with PCOS to determine the effects of obesity. Results: A total of 1,153 proteins were identified, of which 41 and 19 proteins were differentially expressed in the overweight/obese PCOS group vs. the control group, and in the normal-weight PCOS group vs. the control group, respectively. Bioinformatics analyses showed that the inflammatory, immunological, and metabolic-related biological processes were co-enriched in both subgroups of PCOS. Apolipoprotein A-II, complement C5, fetuin-B, and stromal cell-derived factor 1 were found to be involved in various processes and were validated using the ELISA analysis. From clinical features and proteomic data, obesity was found to worsen follicular development disturbances in PCOS. Conclusion: In this proteomic study, a panel of proteins were found differentially expressed in the follicular fluid of PCOS. Inflammatory, immunological, and metabolic abnormalities were identified inside the intra-follicular environment, which could be aggravated by obesity. The identified proteins were correlated with follicular growth and may be considered as candidate biomarkers as well as therapeutic targets of PCOS.

Dataset Information

Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.

Publications

Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets