Metformin Plus Liraglutide Ups Pregnancy in Women with PCOS, Obesity


The GLP-1 receptor agonist/metformin combination did not support weight loss in this population but did increase pregnancy rates per in vitro embryo transfer.

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Obese women with polycystic ovarian syndrome (PCOS) who have experienced infertility have higher pregnancy rates (PR) per invitro embryo transfer (ET) when liraglutide is added to metformin therapy.
Similar weight loss is experienced by women with PCOS who take metformin and liraglutide as by those who take metformin alone.

The glucagon-like peptide-1 (GLP-1) receptor has been implicated in regulating the reproductive system in animal studies. Since obese women with PCOS often have problems with infertility, the authors wondered whether or not the GLP-1 receptor agonist, liraglutide would affect pregnancy rates in this population.

Mojca Sever, MD, PhD and colleagues at University Medical Centre Ljubljana, in Ljubljana, Slovenia sought to evaluate the impact of low-dose liraglutide when added to metformin on the in vitro fertilization pregnancy rate in obese women with PCOS. They presented their findings at this year’s ENDO 2018 annual meeting.

The Study

The authors conducted a prospective randomized open-label study looking at 28 infertile obese women with PCOS. Subjects were randomized to receive metformin alone or metformin in combination with liraglutide 1.2mg daily for 12 weeks.

The Results

Weight loss was not significantly different between the groups (average 7 kg and 7.5 kg for the metformin group and the combined group respectively).
The rate of pregnancy for each embryo transfer was higher in the combination group compared to the metformin alone group (85.7% vs 28.6%; P =0.03).
The total pregnancy rate over 12 months was higher in the combination group compared with the metformin-alone group (69.2% vs 35.7%).
There were no differences in the dosage of stimulation, number of retrieved oocytes, number of mature, fertilized and degenerated oocytes, number of embryos and blastocysts at day five and number of transferred embryos.

Implications for Physicians

• Physicians treating infertile women with PCOS may consider adding liraglutide to metformin therapy if infertility persists.
• Clinicians may counsel women that the combined treatment may also yield similar weight loss to metformin therapy alone.

Dr Sever: “Our observations are not definitive, but do encourage further exploration of the impact of preconception treatment with GLP-1 receptor agonists on reproductive outcomes in different obesity-related populations”.

Abstract: Sever MJ, Salamun V, Bokal EV, Janez A. GLP1 receptor agonist liraglutide increased pregnancy rates in obese women with PCOS undergoing in vitro fertilization: a pilot randomized study. Presented at: The Endocrine Society Annual Meeting (ENDO 2018); March 2018; Chicago. OR33-3


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