New national data reveal a sharp rise in GLP-1 prescriptions for young women, but low contraception use leaves many at risk of unintended pregnancy and uncertain outcomes for their babies.
Study: Incidence of GLP-1 receptor agonist use by women of reproductive age attending general practices in Australia, 2011–2022: a retrospective open cohort study. Image credit: Tetiana_Kryvous/Shutterstock.com
A new study in the Medical Journal of Australia examines the use of glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) in reproductive-age women in Australia to effectively manage type 2 diabetes mellitus, along with contraception overlap and pregnancy incidence in this population.
Introduction
GLP-1 RAs act like the natural hormone GLP-1, stimulating insulin secretion in the presence of high blood sugar levels. Initially investigated for the management of diabetes, their marked weight-loss induction effects led to their increasing use off-label for weight loss.
About 1% of Australian women of reproductive age have type 2 diabetes, and more than 40% of women with type 2 diabetes are also overweight or obese. Consequently, 1% of pregnancies are complicated by type 2 diabetes, vs 50% of pregnancies with overweight or obesity. Preconception care is essential for women with diabetes or excess body weight to improve pregnancy outcomes, particularly since 40% of pregnancies in Australia are unplanned.
The use of GLP-1 RAs for weight management is likely to improve fertility because of even modest weight loss. Yet, their safety during pregnancy remains unclear. Animal studies indicate fetal growth restriction, ossification delay, skeletal variants, and reduced maternal weight gain, though more recent human evidence, including a 2024 cohort of 938 pregnancies, suggests no increased risk of major congenital malformations compared with insulin. However, safety concerns extend beyond malformations, and other potential adverse pregnancy outcomes were not examined.
Current UK guidelines advise against their use in pregnancy and recommend concurrent effective contraception for women using them during their reproductive years. Yet few women who start GLP-1 RAs are on contraception. A significant proportion of these women become pregnant soon after beginning treatment with these agents.
The current study sought to understand GLP-1 RA use among Australian women in their reproductive years, along with compliance with contraception recommendations, and the incidence of pregnancy, in this subgroup.
About the study
The study included 1,635,684 women aged 18 to 49, of whom 18,010 were first prescribed GLP-1 Ras between January 1, 2011, and July 31, 2022. Of these, 3,739 women, making up 21% of the total, were reported to have type 2 diabetes.
Study findings
The incidence of GLP-1 RA prescription in the subgroup of reproductive-age women with type 2 diabetes stood at 13 per 1,000 women in 2011, increasing to 88.5 per 1,000 women in 2022. Women in the same age group who did not have type 2 diabetes had an incidence of 15 per 1,000 women in 2022, compared to zero at baseline.
Of the 6,954 women who received GLP-1 RA prescriptions in 2022, 91% of them did not have type 2 diabetes, indicating that off-label use made up most prescriptions.
About 21% of the cohort had sufficient electronic health record data to determine contraception overlap with the period of GLP-1 RA initiation. In this subgroup, about 17% of treated women with type 2 diabetes were on contraception at this time vs 23% of those without diabetes. About 6% and 9% of women on GLP-1 RAs with and without type 2 diabetes used long-acting reversible contraception methods, compared to 11% overall for Australian women.
There were 232 pregnancies among 10,781 women within six months of being prescribed these agents, considering only women who could be followed up for at least this period. Women on contraception when they started GLP-1 RAs were 40% less likely to conceive over the next six months.
About 4% of women aged 18-29 who had type 2 diabetes and were on GLP-1 RAs became pregnant, the highest rate among all age groups. Conversely, among non-diabetic women, the highest rate was 6% among those aged 30-34 years. Women who conceived within six months of starting GLP-1 RAs were twice as likely to have polycystic ovary syndrome compared to those who did not.
Conclusions
GLP-1 RAs are being increasingly prescribed among women within the reproductive period in Australia, irrespective of the presence of type 2 diabetes. Most women prescribed these medications did not have type 2 diabetes. This suggests that these are being increasingly used off-label for weight loss and other non-diabetes indications.
More than 75% of these women do not use contraceptives when initiating the use of these agents. This indicates the need for more research to determine guidelines that can ensure GLP-1 RAs are used safely and effectively in this group of women, including those with type 2 diabetes, obesity or overweight, and polycystic ovary syndrome.
The study also noted that the rapid rise in prescribing since 2020 coincided with the approval and PBS listing of semaglutide in Australia, which likely drove much of the recent increase. There is an urgent need to identify the potential effects of these drugs on the fetus.
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