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Combination liraglutide, metformin therapy increases pregnancy rate in obesity, PCOS

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May 8, 2018

Women with obesity and polycystic ovary syndrome randomly assigned to combination metformin plus liraglutide therapy were nearly twice as likely to achieve pregnancy via in vitro fertilization over 12 months vs. similar women assigned to metformin alone, according to findings from a small pilot study published in the European Journal of Endocrinology.

The potential beneficial effects of liraglutide (Victoza, Novo Nordisk), a GLP-1 receptor agonist, on IVF outcomes in women with PCOS and obesity have not been addressed yet, Vesna Salamun, MD, of the department of human reproduction at University Medical Centre Ljubljana, Slovenia, and colleagues wrote in the study background. Weight loss before IVF has been associated with improved fertility and live birth rates, as well as a decrease in number of IVF cycles needed to achieve pregnancy.

“Since liraglutide is an effective insulin-sensitizing agent, there is a theoretical assumption that weight loss will improve the reproductive outcomes by weight loss,” the researchers wrote. “Moreover, new animal data suggest that GLP-1 receptor agonists play a role in the regulation of the hypothalamus-pituitary-ovary axis by neuroendocrine modulation of gonadotropin-releasing hormones.”

Salamun and colleagues analyzed data from 28 women with obesity and PCOS, diagnosed according to Rotterdam criteria, who participated in a 12-week, open-label, randomized trial (mean age, 31 years; mean BMI, 36.7 kg/m²). Between September 2014 and May 2015, researchers randomly assigned women to 1,000 mg metformin twice daily (n = 14; infertility duration, 32.7 months) or 1,000 mg metformin plus 1.2 mg liraglutide once daily for 12 weeks (n = 13; infertility duration, 56.2 months). In the liraglutide arm, metformin was titrated from an initial dose of 500 mg to 1,000 mg over 12 days before liraglutide was added (initial liraglutide dose, 0.6 mg, increased to 1.2 mg after 3 days). Researchers promoted lifestyle interventions in both groups, including a reduced-calorie diet consisting of 50% carbohydrates, 20% proteins and 30% fat (mostly mono- and polyunsaturated). IVF was offered to all women who completed treatment after a 1-month washout period.

Fasting blood samples were collected at baseline and 12 weeks to measure levels of glucose, insulin, androstenedione, total and free testosterone and sex hormone-binding globulin. IVF pregnancy rate was defined as the number of clinical pregnancies confirmed by ultrasound of fetal cardiac activity, divided by the total number of cycles performed or embryo transfers.

There were no between-group differences in weight loss over 12 weeks; patients in the metformin group lost a mean 7 kg, and patients in the combination therapy group lost a mean 7.5 kg. However, the pregnancy rate per egg transfer was higher in the combination therapy group (85.7%) vs. the metformin-only group (28.6%; P = .03).

In the combination group, 9 of 13 women (69.2%) became pregnant in 1 year, including one who conceived spontaneously after treatment, six after IVF and two spontaneous after an unsuccessful IVF. In the metformin group, five of 14 women (35.7%) became pregnant in 1 year, including one immediately after treatment, two after an IVF procedure and two spontaneous pregnancies after an unsuccessful IVF.

“Our observations are not definitive, but do encourage further exploration of the efficacy and safety of this class of medications on reproductive outcomes in different obesity-related populations,” the researchers wrote. “The precise role of liraglutide in the relationship between the GLP-1 axis and female reproduction remains to be elucidated, in particular the GLP-1 impact on endometrial quality and receptivity.” – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.

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