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Pregnancy rate doubles with exenatide vs. metformin in PCOS

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August 28, 2017

Ying Zhang
Ying Zhang

Women with polycystic ovary syndrome and overweight or obesity assigned twice-daily exenatide therapy for 12 weeks were twice as likely to achieve pregnancy than those assigned metformin, according to findings published in Clinical Endocrinology.

The open-label, prospective, randomized controlled trial, according to researchers, is the first to demonstrate that short-term exenatide therapy (Byetta, AstraZeneca) was superior to metformin therapy in increasing natural pregnancy rates, improving menstrual cycle frequency and decreasing BMI, fat mass, insulin resistance and inflammatory markers in women with PCOS and overweight or obesity over 24 weeks.

“Short-term exenatide therapy was linked to significant weight loss and central adiposity reduction, which may further explain the improvements in insulin resistance, inflammatory markers and menstrual cycle, which may contribute to increasing pregnancy rates in overweight or obese women with PCOS,” Ying Zhang, PhD, of the department of endocrinology, at the Third Affiliated Hospital of Guangzhou Medical University, Guangdong, China, told Endocrine Today. “The current study is the first to provide preliminary data that short-term exenatide treatment can produce greater increases in the chance of pregnancy than metformin treatment.”

Zhang and Xin Liu, PhD, of the department of endocrinology at the Third Affiliated Hospital of Guangzhou Medical University in Guangdong, China, and colleagues analyzed data from 176 women with PCOS and BMI at least 24 kg/m² who did not have diabetes, had not used contraception for more than 2 years, had a male partner with a normal semen test and had not become pregnant. Researchers randomly assigned patients to 1,000 mg metformin twice daily or 10 µg exenatide twice daily for 12 weeks; women were asked to use barrier contraception exclusively during this time. In the second 12-week period, patients assigned exenatide switched to 1,000 mg metformin therapy; patients already taking metformin remained on the therapy; couples were instructed to have regular copulation two to three times weekly. All patients were guided with the same diet and physical activity recommendations. At baseline and 12 weeks, women underwent a 75-g oral glucose tolerance test and provided fasting blood samples to measure testosterone, sex hormone-binding globulin, total cholesterol, triglycerides, LDL and HDL cholesterol and high-sensitivity C-reactive protein levels, as well as a urine pregnancy test.

At 24 weeks, 158 patients completed the protocol (80 women assigned metformin and 78 women assigned exenatide).

Women in both groups experienced a decrease in body weight, with those in the exenatide group losing more (mean, –4.29 kg) than those assigned metformin (mean, –2.28 kg). BMI and waist circumference decreased in both groups, whereas those assigned exenatide saw a decrease in android fat mass percentage (P < .001). At baseline, 34 women overall (22%) had impaired glucose tolerance; among these, 54% of women assigned metformin and 57% of women assigned exenatide returned to normal glucose tolerance by the first 12 weeks. Women in the exenatide group also experienced a decrease in high-sensitivity C reactive protein (P < .05).

The rate of natural pregnancy was higher following exenatide therapy vs. metformin (43.6% vs. 18.7%), according to researchers. Menstrual cycle also became more regular in both groups, with greater improvement observed in those assigned exenatide (P < .001). The most frequent adverse events reported were mild or moderate gastrointestinal discomfort.

“The fact that subjects lost more weight with EXE may partly explain why the participants in the EXE group had more regular menstrual cycles than those in the MET group,” the researchers wrote. – by Regina Schaffer

 

For more information:

Ying Zhang, PhD, can be reached at the Third Affiliated Hospital of Guangzhou Medical University, NO.63, Duobao Road, Liwan District, Guangzhou, Guangdong, 510150, PR China; email: zhangying30412@163.com.

Disclosures: The authors report no relevant financial disclosures.