Continuing Metformin Reduces PCOS Pregnancy Risks

Continuing metformin throughout the first trimester in women with polycystic ovary syndrome (PCOS) showed the potential to reduce miscarriage risk (odds ratio [OR], 0.64) and increase clinical pregnancy rates (OR, 1.57) compared with placebo. A meta-analysis of 12 randomized controlled trials involving 1708 women suggested that stopping metformin at pregnancy confirmation might be less beneficial than continuation through the first trimester.
METHODOLOGY:
Researchers conducted a systematic review and meta-analysis of randomized controlled trials evaluating metformin started preconception and continued at least until positive pregnancy test compared with placebo or no treatment in women with PCOS.
The analysis included 12 trustworthy studies with 1708 participants, with trials conducted across 14 countries spanning five continents, all graded as low to moderate quality evidence.
The primary outcome measure focused on miscarriage rate, defined as pregnancy loss prior to 20 completed weeks of gestation, while secondary outcomes included clinical pregnancy and live birth rates.
Investigators performed indirect comparisons between treatment groups using the Bucher technique to evaluate clinical pregnancy, miscarriage, and live birth rates for metformin treatment continued throughout first trimester vs stopped at a positive pregnancy test.
TAKEAWAY:
Women receiving preconception metformin continued throughout the first trimester had higher clinical pregnancy rates (OR, 1.57; 95% CI, 1.11-2.23), potential reduction in miscarriage (OR, 0.64; 95% CI, 0.32-1.25), and possible increase in live birth (OR, 1.24; 95% CI, 0.59-2.61) compared with placebo or no treatment.
Participants who stopped metformin once pregnant showed an increased clinical pregnancy rate (OR, 1.35; 95% CI, 1.01-1.80) but suggested higher miscarriage risk (OR, 1.46; 95% CI, 0.73-2.90) compared with placebo or no treatment.
Indirect comparisons consistently favored continuing metformin through first trimester vs stopping at pregnancy confirmation for clinical pregnancy (OR, 1.16; 95% CI, 0.74-1.83), miscarriage (OR, 0.44; 95% CI, 0.17-1.16), and live birth (OR, 1.14; 95% CI, 0.41-3.13).
IN PRACTICE:
'Women with PCOS have been shown to have a fivefold increased risk per year of developing insulin resistance and subsequent type 2 diabetes. Insulin resistance has been shown to be independently associated with a higher risk of miscarriage. Metformin acts by decreasing gluconeogenesis, lipogenesis and enhancing glucose uptake, all of which in turn reduce insulin resistance,' wrote the authors of the study.
SOURCE:
The study was led by James Cheshire, PhD, Birmingham Women's and Children's NHS Foundation Trust in Birmingham, England. It was published online in American Journal of Obstetrics and Gynecology .
LIMITATIONS:
According to the authors, the main limitation was the inherent heterogeneous nature of the study population and the overall low quality of evidence. Women with PCOS have different phenotypes and varying degrees of hyperandrogenism and insulin resistance, which could not be accounted for in the analyses. Additionally, many studies did not subdivide pregnancy outcome data by body mass index (BMI), preventing meaningful analyses in BMI subgroups. The limited outcome data in spontaneously conceiving populations (only 30 women from two studies) make it difficult to extrapolate findings to this group.
DISCLOSURES:
The authors reported having no conflicts of interest. The study received no external funding.

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Associated Press

13 minutes ago

• Associated Press

Novo Nordisk advances early-stage obesity medication, amycretin, to phase 3 clinical development based on early-phase clinical trial results in people with obesity or excess weight, published in The Lancet

PLAINSBORO, N.J., June 20, 2025 /PRNewswire/ -- Today, results from two early-phase clinical trials evaluating Novo Nordisk's amycretin, an innovative investigational obesity treatment designed to target appetite regulation, were published in The Lancet.1 In a phase 1b/2a clinical trial of 125 adults with overweight or obesity, once-weekly subcutaneous amycretin appeared to be safe and tolerable in trial participants, who also achieved significantly greater weight loss across the full range of doses investigated versus placebo.1 A related phase 1 trial of once-daily oral amycretin in adults with obesity or overweight also showed that treatment was safe and tolerable with an observed reduction in body weight compared to placebo.2 No weight loss plateau was observed in either trial at the end of the respective treatment durations.1,2 Data on subcutaneous amycretin is scheduled to be presented on Sunday, June 22nd, during a late-breaking poster session at the American Diabetes Association's® (ADA) 85th Scientific Sessions.1 'We are pleased with the promising results of amycretin and the feedback from regulatory authorities and are excited to advance both subcutaneous and oral versions of this molecule into phase 3 development for weight management. At Novo Nordisk, we understand that addressing obesity is a complex challenge that many patients face. These results reflect our robust pipeline in obesity, our focus on progressing scientific innovation and expanding the range of options available to patients and healthcare professionals,' said Martin Holst Lange, executive vice president for Development at Novo Nordisk. 'We remain steadfast in our mission to discover and develop therapies that can have a meaningful impact in the lives of those affected by obesity.' Results from the phase 1b/2a trial of subcutaneous amycretin showed treatment-emergent adverse events (TEAEs) were mild or moderate in severity and increased in frequency in a dose-dependent manner. The most frequent reported TEAEs were gastrointestinal in nature. Compared to placebo, participants receiving amycretin observed greater weight loss across the full range of doses investigated.1 Subcutaneous amycretin at multiple doses demonstrated greater weight reduction than placebo at the end of the trial. Participants who received the highest doses (up to 60 mg) reported body weight reductions of up to 24.3% versus 1.1% with placebo after 36 weeks of treatment. Results from this first-in-human phase 1b/2a study support further investigation of potential weight-loss efficacy of amycretin. Results from the published phase 1 trial of oral amycretin showed that the most common TEAEs were related to gastrointestinal symptoms (mainly nausea and vomiting) and decreased appetite; these were most frequent for the higher doses. Trial participants receiving the study treatment demonstrated significantly greater weight loss across the full range of doses investigated versus the placebo group.2 Exploratory results showed participants taking 100 mg per day of oral amycretin achieved a mean weight loss of 13.1% versus 1.2% with placebo after 12 weeks.2 Based on these phase 1 results, longer evaluation with more participants is warranted to substantiate the full efficacy findings of oral amycretin on body weight reductions and changes in metabolic parameters. Novo Nordisk will advance both subcutaneous and oral amycretin formulations straight to phase 3 development for weight management based on these and other completed clinical studies, as well as feedback received from regulatory authorities. About amycretin Amycretin is a unimolecular long-acting GLP-1 and amylin receptor agonist under development by Novo Nordisk, to provide a treatment for adults with overweight or obesity and as a treatment for adults with type 2 diabetes. Amycretin is under investigation for oral and subcutaneous administration, and is not approved in the US for weight loss. About the phase 1b/2a subcutaneous amycretin trial The phase 1b/2a trial was a randomized, placebo-controlled, single-center, double-blinded study of 125 participants assessing the safety, tolerability, pharmacokinetics, and effects on body weight after subcutaneous administration of amycretin in people with overweight or obesity.1 Adults with a body mass index of 27-39.9kg/m2 and glycated hemoglobin (HbA1c) <6.5% were eligible for the trial.1 The trial was conducted in 5 parts: a single ascending dose (Part A) for determination of pharmacokinetics and starting dose for the first multiple dose cohort in which the safety and tolerability were explored using dose escalation until 36 weeks of total treatment duration (Part B).1 Lastly, in the multiple ascending dose – dose response parts, body weight loss was explored for up to 36 weeks of dosing by escalating to dose levels of 1.25 mg, 5 mg, and 20 mg, respectively, dosed for 12 weeks (Part E, D and C).1 About the phase 1 oral amycretin trial The phase 1 single-center, randomized, placebo-controlled study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses (Part A) and multiple ascending doses (Part B, 10 days of treatment; Part C/D, 12 weeks of treatment) of 144 adult participants with overweight or obesity.2 The primary endpoint was the number of treatment-emergent adverse events (TEAEs) observed in the trial. The trial evaluated the single-ascending dose and multiple ascending doses for oral amycretin, up to 2 times 50 mg, in people with overweight or obesity, with a total treatment duration of up to 12 weeks.2 About obesity Obesity is a serious chronic, progressive, and complex disease that requires long-term management.3-5 One key misunderstanding is that this is a disease of just lack of willpower, when in fact there is underlying biology that may impede people with obesity from losing weight and keeping it off.3,5 Obesity is influenced by a variety of factors, including genetics, social determinants of health, and the environment.6,7 The prevalence of overweight and obesity is a public health issue that has severe cost implications to healthcare systems.8,9 In the US, about 40% of adults live with obesity.10 About Novo Nordisk Novo Nordisk is a leading global healthcare company that's been making innovative medicines to help people with diabetes lead longer, healthier lives for more than 100 years. This heritage has given us experience and capabilities that also enable us to drive change to help people defeat other serious chronic diseases such as obesity, rare blood, and endocrine disorders. We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term, and do business in a financially, socially, and environmentally responsible way. With a US presence spanning 40 years, Novo Nordisk US is headquartered in New Jersey and employs over 10,000 people throughout the country across 12 manufacturing, R&D and corporate locations in eight states plus Washington DC. For more information, visit Facebook, Instagram, and X. Novo Nordisk is committed to the responsible use of our semaglutide-containing medicines which represent distinct products with different indications, dosages, prescribing information, titration schedules, and delivery forms. These products are not interchangeable and should not be used outside of their approved indications. Learn more at Contacts for further information References © 2025 Novo Nordisk All rights reserved. US25SEMO01477 June 2025 View original content to download multimedia: SOURCE NOVO NORDISK INC.

Newsweek

32 minutes ago

• Newsweek

Bride Spends Months Dieting for Wedding—Then Gets Devastating Diagnosis

Based on facts, either observed and verified firsthand by the reporter, or reported and verified from knowledgeable sources. Newsweek AI is in beta. Translations may contain inaccuracies—please refer to the original content. For Cynthia Donovan, looking flawless on her wedding day in 2011 was a non-negotiable. But the relentless pursuit of perfection would eventually derail her health and fertility. "I got engaged and thought, 'I have to get into the best shape of my life,'" Donovan said. "So I kicked into overdrive." Prior to wedding planning, the registered dietitian from New York, already led a health-conscious lifestyle. She ate clean—plenty of vegetables and lean meats—and worked out five days a week. But once a ring was on her finger, she amped up her regimen: exercising seven days a week, sometimes for up to three hours a day. "I would exercise before work and then run after work. It was partly for stress relief, but I wasn't fueling my body properly, and that created even more stress physically," she said. She began tracking everything and wouldn't eat more than 1,500 calories. The now 39-year-old told Newsweek: "I was eating healthier and calculating my calories based on height. That's another misconception, that our bodies are just calculations." Despite being praised by others for her discipline and physique, Donovan's body was showing signs of distress. After going off birth control in hopes of checking her fertility, her period didn't return. "My doctor told me it was normal post-pill amenorrhea and to wait three to five months. But with the wedding approaching, I went back on the pill," she said. "What I didn't realize was that my period wasn't going to come back any time soon." That decision led to a grueling five-year journey of misdiagnoses, hormone therapies, supplements, acupuncture, and mounting frustration. 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"You can get in shape, but it doesn't have to be extreme. It shouldn't cost you your health," Donovan said. "I want women to feel free—not stressed—around food." Is there a health issue that's worrying you? Let us know via health@ We can ask experts for advice, and your story could be featured on Newsweek.

Fox News

7 hours ago

• Fox News

Mysterious 'dragon man' skull found in the 1930s finally identified

A mysterious human skull found in the 1930s has been identified as an existing species after once being thought to be a new species all together, according to researchers. The studies — posted in the journals Cell and Science — have identified the 146,000-year-old skull known as "dragon man" has been categorized as a Denisovan. The researchers revealed that the Denisovans were discovered by their genomes and proteins to identify them. However, the reason it took so long to identify was that the attempts to extract DNA from a tooth failed. Researchers also tried extracting DNA from the Harbin cranium as well, which also failed. When those methods failed, researchers turned to using dental calculus, which uses calcified dental plaque. The calcified dental plaque could hold and protect DNA due to its dense crystalline structure that resists degradation in various environments. Researchers used bleach on the dental plaque in order to eliminate any possible modern-day DNA. Once extracted, researchers began to compare the genetic material discovered to previous samples. The researchers found that the "dragon man" was not a new species but was a Denisovan and the very first intact specimen to date. According to the researchers, Denisovans coexisted with modern-day humans and are closely related to Neanderthals. The "dragon man" was discovered in mysterious circumstances when a Chinese laborer working on a bridge over the Songhua River found it. The man kept the Harbin cranium well hidden as he was instructed to hide it from the Japanese army. The skull was donated shortly before his death in 2018, after which his family relocated the skull and gave it to the Geoscience Museum, Hebei GEO University professor Qiang Ji. While there are limitations to this study, the researchers said there is still so much to learn moving forward. It was called "dragon man" because it was found in the Heilongjiang province of China, which translates to Black Dragon River. Fox News Digital's Julia Musto contributed to this story.