Study finds reassuring signs for diabetic and weight loss drug use around pregnancy, but questions remain

A study by an international group of researchers finds popular diabetes and weight-loss drugs are not linked to pregnancy complications in most women with diabetes.

The results of the study have just been published in The Lancet Obstetrics, Gynaecology & Women’s Health and presented at the Annual Meeting of The European Association for the Study of Diabetes (EASD) in Milan, Italy, this week.

They show that following a review and meta-analysis of available studies, use of glucagon-like peptide-1 receptor agonists known more commonly as (GLP-1 RA) drugs for diabetes and weight management in women living with diabetes, are not associated with adverse pregnancy outcomes in most cases. 

However, the international panel of authors, which include Professor Claire Meek from the Leicester Diabetes Research Centre and Leicester NIHR Biomedical Research Centre, say more research to address this field is critical to address large evidence gaps and to keep pace with the huge and accelerating increase in women of reproductive age using these drugs. 

Professor Meek said: “Millions of women are now using GLP-1 receptor agonists, but there remain important unanswered questions about their impact on fertility, pregnancy, and maternal and child health. Women deserve clearer evidence to guide some of the most important healthcare decisions of their lives. As new weight loss medications enter clinical practice at pace, generating robust evidence for women before, during, and after pregnancy has never been more urgent.”

The prevalence of diabetes in pregnancy, including type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM), continues to rise globally, underscoring the need to optimise maternal metabolic health before conception – that is, make women as healthy as possible before they conceive, including improving their blood sugar status and weight loss if needed. 

GLP-1 RA-based therapies offer substantial benefits for weight reduction and blood sugar control and are increasingly prescribed to women of reproductive age. However, their safety and effectiveness before, during, and after pregnancy remain uncertain. 

To investigate the available evidence, the authors did a systematic review and used seven studies with more than 43,000 participants exposed to GLP-1 RAs in their meta-analysis. 

Among these studies, 6 of the 7 assessed exposure in the first trimester of pregnancy; 1 of the 7 assessed exposure at any point in the 12 months pre-pregnancy, which could include exposure in early pregnancy. The exact timings of exposure in terms of weeks of pregnancy were often not well documented.

The meta-analysis suggested no significant associations between GLP-1 RA exposure and risk of preterm birth, stillbirth or neonatal death, caesarean section, pregnancy hypertensive disorders or pre-eclampsia, or small-for-gestational age infant. 

There was a slightly higher risk of early pregnancy loss but the authors urge caution over this as deliberate termination and miscarriage were counted as the same outcome. Evidence regarding miscarriage, pregnancy exposure to GLP-1 RA beyond the first trimester, and postpartum use of these drugs remains limited.

The study on the use of GLP-1 medicines during pregnancy planning, pregnancy and after birth in women with diabetes, is the first of its kind and involved research on more than 43,000 women, advice from 42 specialists, and feedback from women with personal experience.

It suggests that stopping GLP-1 medicines in early pregnancy does not increase the risk of birth defects compared with not taking the drugs at all. However, there is still limited evidence about miscarriage risk, use later in pregnancy, and use while breastfeeding.

The experts say GLP-1 medicines can be helpful for improving health and managing weight before pregnancy in women with type 2 diabetes, but more research is needed to understand their safety and effects throughout pregnancy, breastfeeding and beyond.

They also highlight that evidence regarding GLP-1RA use in the second and third trimesters remains extremely limited, and robust data on maternal, fetal and offspring outcomes are needed. 

There has also been very little research on using GLP-1 medicines following birth.  Available studies suggest that only tiny amounts, if any, pass into breast milk when the drugs are given by injection. However, there is not yet enough evidence to know whether they are completely safe for breastfed babies, especially for tablet forms of the drugs.

Professor Meek added: “Overall, current evidence is insufficient to define the benefits and risks of GLP-1RA therapy across the reproductive life course. Large prospective studies are urgently required to evaluate maternal, fetal and infant outcomes, alongside longer-term metabolic and developmental consequences for both mother and child.”