Ozempic’s hidden pregnancy risk few women know about

A groundbreaking study, spearheaded by Flinders University and published in the esteemed Medical Journal of Australia, has cast a critical spotlight on the prescribing patterns of GLP-1 receptor agonists—a class of medications increasingly popular for weight management—among Australian women of reproductive age. The research reveals a significant oversight in clinical practice: the vast majority of these women are not using effective contraception, despite well-documented warnings and potential risks associated with these drugs during pregnancy. This finding underscores a pressing public health concern, highlighting a disconnect between clinical guidelines and real-world application, with potentially profound implications for maternal and fetal health.

The Alarming Data: A Gap in Contraception Use

The comprehensive study meticulously analysed data from over 1.6 million women aged 18 to 49 who attended general practices across Australia between 2011 and 2022. The findings were stark: out of the 18,010 women who were newly prescribed GLP-1 receptor agonists during this period, a mere 21% had reported using any form of contraception. This figure is particularly concerning given the established teratogenic risks identified in animal studies and the growing off-label use of these medications for weight loss in a demographic highly susceptible to unplanned pregnancies.

Associate Professor Luke Grzeskowiak, a pharmacist and the lead author of the study from Flinders University’s College of Medicine and Public Health, articulated the gravity of the situation. "We’re seeing widespread use of these medications among women of childbearing age, but very little evidence that contraception is being considered as part of routine care," he stated. "These medications can be incredibly helpful, but they’re not risk-free, especially during pregnancy."

The research further revealed that 2.2% of women initiated on GLP-1 treatment became pregnant within six months, with pregnancy rates notably higher among younger women with diabetes and among non-diabetic women in their early thirties. Importantly, the study confirmed that women who were using contraception at the time of prescribing had a significantly lower risk of pregnancy, unequivocally demonstrating the protective role of effective birth control.

The Rise of GLP-1 Receptor Agonists: From Diabetes to Weight Loss Phenomenon

To fully appreciate the scope of this issue, it is crucial to understand the trajectory of GLP-1 receptor agonists. Originally developed in the early 2000s for the management of type 2 diabetes, drugs like exenatide (Byetta) and liraglutide (Victoza) mimic the action of glucagon-like peptide-1, a hormone that helps regulate blood sugar. Their mechanism involves slowing gastric emptying, increasing insulin secretion in response to high glucose, suppressing glucagon release, and promoting satiety. These effects not only aid in glycemic control but also lead to significant weight loss, a side effect that soon became a primary indication for their use.

The landscape dramatically shifted with the introduction of semaglutide (Ozempic, Wegovy) and later tirzepatide (Mounjaro). Semaglutide, initially approved for type 2 diabetes, gained widespread attention for its potent weight-loss capabilities, leading to the approval of a higher-dose formulation (Wegovy) specifically for chronic weight management in individuals with obesity or overweight with comorbidities. This marked a pivotal moment, transforming GLP-1s from niche diabetes treatments into mainstream weight-loss solutions.

The global obesity epidemic, recognised by the World Health Organization as a major public health challenge, has fuelled the demand for effective pharmacological interventions. In Australia, the prevalence of overweight and obesity continues to rise, with over two-thirds of adults classified as overweight or obese. This backdrop has contributed to the explosive popularity of GLP-1 agonists, often amplified by media coverage, social media trends, and word-of-mouth.

The Flinders study highlighted this shift, finding that in 2022 alone, more than 6,000 Australian women began treatment on GLP-1s, and over 90% of those did not have a diabetes diagnosis. This indicates a profound expansion of their use into the general population, particularly among those seeking weight loss, which inherently includes a large cohort of women in their reproductive years.

Understanding the Potential Risks: What Animal Studies Tell Us

While human data on GLP-1 exposure during pregnancy remains limited due to ethical constraints on conducting trials in pregnant individuals, animal studies provide critical insights into potential risks. A comprehensive review conducted by the University of Amsterdam, for instance, linked GLP-1 exposure during pregnancy to concerning outcomes such as reduced fetal growth and skeletal abnormalities.

The implications of these animal studies are significant. Regulatory bodies worldwide, including the Therapeutic Goods Administration (TGA) in Australia, the Food and Drug Administration (FDA) in the United States, and the European Medicines Agency (EMA), classify many GLP-1 receptor agonists with warnings against use during pregnancy. For example, semaglutide is typically classified in pregnancy category B3 in Australia (or equivalent Category C in the US for some formulations/drugs in this class), advising against use in pregnancy and recommending discontinuation well in advance of planned conception due to its long half-life (approximately one week for semaglutide, requiring a washout period of several weeks, sometimes two months, before attempting conception).

The mechanism of potential harm is thought to involve both direct fetal exposure through placental transfer and indirect effects on maternal metabolism, which can impact the fetal environment. Alterations in maternal glucose regulation, rapid weight loss, and potential direct effects of the drug on fetal development are all areas of concern. Given that some GLP-1s have a prolonged half-life, their effects can persist in the body for several weeks after discontinuation, necessitating careful planning for women considering pregnancy.

The Contraception Conundrum: A Call for Consistent Clinical Practice

The disparity between international clinical advice and Australian practice revealed by the Flinders study is alarming. As Associate Professor Grzeskowiak noted, "Whilst the UK advises that women using GLP-1 receptor agonists should avoid pregnancy and use effective contraception, this advice is not being followed consistently in Australian clinical practice."

This gap suggests several underlying issues:

• Lack of Prescriber Awareness: While prescribers are generally aware of pregnancy warnings for medications, the rapid surge in GLP-1 use for weight loss, combined with the focus on the primary indication, may lead to reproductive health discussions being overlooked.
• Patient Education Deficiencies: Patients, often eager for weight loss, may not be adequately informed about the pregnancy risks or the necessity of effective contraception. The ‘off-label’ use for weight loss in some instances might also obscure clear guidelines.
• Time Constraints in Consultations: General practice consultations are often time-pressured, making comprehensive discussions on all potential side effects, including detailed reproductive health counselling, challenging.
• Perceived Urgency of Weight Loss: For some patients, the immediate benefits of weight loss may overshadow future pregnancy planning, leading to a less cautious approach.

The Royal Australian College of General Practitioners (RACGP) and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) play crucial roles in disseminating best practice guidelines. The study’s findings highlight an urgent need for these bodies, in conjunction with the TGA, to reinforce and clarify guidelines specifically for GLP-1 prescribing to women of childbearing potential.

Polycystic Ovary Syndrome (PCOS) and Unintended Fertility

An intriguing and equally critical finding of the study was the observation that women with polycystic ovary syndrome (PCOS) were twice as likely to conceive while on GLP-1 treatment. PCOS is a common endocrine disorder affecting up to 1 in 10 women of reproductive age, often characterised by hormonal imbalances, irregular periods, and insulin resistance. Weight management is a cornerstone of PCOS treatment, as obesity can exacerbate symptoms and impair fertility.

The link between GLP-1 use, weight loss, and increased conception rates in women with PCOS suggests that these medications may inadvertently improve fertility by addressing underlying metabolic issues. While this could be a desired outcome for some women actively trying to conceive, it becomes a significant risk factor for unplanned pregnancies when contraception is not in place. This underscores the need for particularly vigilant counselling for women with PCOS starting GLP-1s, ensuring they are fully aware of their potentially enhanced fertility and the absolute necessity of effective contraception if pregnancy is to be avoided.

Broader Implications and Future Directions

The Flinders University study is more than just a warning; it is a call to action for multiple stakeholders within the healthcare ecosystem.

Public Health Policy and Guidelines: There is an immediate need for clearer, more explicit national guidelines for prescribers of GLP-1 receptor agonists to women of childbearing age. These guidelines should mandate comprehensive reproductive health counselling, including discussions about pregnancy risks, the need for highly effective contraception, and appropriate washout periods if pregnancy is planned. Regulatory bodies like the TGA must ensure that product information clearly communicates these risks in a way that is easily understood by both prescribers and patients.

Prescriber Responsibility and Education: Healthcare professionals, particularly general practitioners, endocrinologists, and bariatric specialists, must integrate reproductive health into every conversation when prescribing GLP-1s. This includes:

• Thorough Patient Assessment: Ascertaining pregnancy status and intentions.
• Counselling on Risks: Explaining known and potential risks to pregnancy.
• Contraception Discussion: Offering and facilitating access to effective contraception, including long-acting reversible contraceptives (LARCs), which are highly effective and user-independent.
• Pre-conception Planning: Advising on appropriate discontinuation and washout periods for those planning pregnancy.

Patient Empowerment and Education: Women must be empowered with accurate information to make informed decisions about their health. Associate Professor Grzeskowiak’s advice is clear: "Our advice is to speak to your GP about the risks and benefits of GLP-1 medicines before taking them, and only take those prescribed by a healthcare professional." Patient advocacy groups can also play a vital role in raising awareness.

Research Imperative: The study authors rightly call for further studies evaluating the impact of these medications on pregnancy and unborn babies in humans. This includes establishing robust pregnancy registries to track outcomes of unintended exposures, conducting observational studies, and investigating the long-term developmental impacts on children exposed in utero. Such data is critical to refine risk assessments and inform future guidelines.

Ethical Considerations: The widespread use of GLP-1s raises ethical questions about balancing the benefits of weight loss and metabolic control with potential fetal risks. The autonomy of women to make reproductive choices must be respected, but this autonomy can only be truly exercised when informed by comprehensive and accurate medical advice.

In conclusion, the Flinders University research has unveiled a critical blind spot in the rapidly expanding use of GLP-1 receptor agonists. While these medications offer significant benefits for weight management and diabetes, their deployment must be accompanied by a rigorous commitment to reproductive health counselling and effective contraception for women of childbearing age. The findings serve as an urgent reminder that patient safety, particularly for vulnerable populations like pregnant women and unborn babies, must remain paramount in all clinical practice. A concerted effort from researchers, prescribers, policymakers, and patients themselves is essential to ensure these powerful medications are used both safely and effectively, without inadvertently compromising the health of future generations.

Acknowledgements: Luke Grzeskowiak receives salary support from a Channel 7 Children’s Research Foundation Fellowship (CRF-210323). We also acknowledge the contributions of members of the SPHERE Centre of Research Excellence in Women’s Sexual and Reproductive Health in Primary Care (SPHERE 2.0 CRE), which is funded by the National Health and Medical Research Council (APP2024717).