GLP-1 receptor agonists in early pregnancy: What ob-gyns should know

A recent meta-analysis of more than 47,000 pregnancies exposed to GLP-1 receptor agonists shortly before or during early pregnancy found no increased risk of several major maternal complications, including gestational diabetes, preterm birth, and hypertensive disorders of pregnancy such as preeclampsia.¹ In this interview, Elizabeth Jasper, PhD, an assistant professor in the division of quantitative and clinical sciences in the department of obstetrics and gynecology at Vanderbilt University Medical Center in Nashville, Tennessee, discusses what these findings mean for practicing OB/GYNs and their patients.

Although the pooled results are reassuring, Jasper notes that the underlying studies are heterogeneous and largely observational, varying in patient populations, medication and dosage, exposure timing, and outcome measurement—limitations that temper the certainty of the evidence. A sensitivity analysis suggesting a possible protective effect against gestational diabetes is hypothesis-generating rather than conclusive, and she cautions against overstating it, given the potential for confounding by body mass index (BMI) and metabolic risk factors.

Also see: GLP-1 RAs linked to broad menstrual adverse event signals in reproductive-aged patients

Jasper also discusses what a more definitive study would require, including clearer exposure definitions, stronger comparison groups, and better control for confounders such as BMI, weight loss, and prior pregnancy history. She explains how the findings support current guidance to discontinue GLP-1 receptor agonists before or upon recognition of pregnancy, and how ob-gyns should coordinate with endocrinologists and primary care physicians when a patient presents pregnant while on these medications. She closes with guidance for counseling patients who discover inadvertent early exposure, as well as those planning a pregnancy while using a GLP-1 receptor agonist.

Contemporary OB/GYN: What is the most clinically meaningful takeaway from this meta-analysis for OB/GYNs whose patients are on GLP-1 receptor agonists when they conceive?

Jasper: For clinicians, the most clinically meaningful takeaway from our meta-analysis is that based on the currently available human data, exposure to GLP-1 receptor agonists shortly before or early in pregnancy was not associated with higher rates of several major maternal complications, including gestational diabetes, preterm birth, and hypertensive disorders of pregnancy. That said, there are few peer-reviewed studies on this topic, and the existing literature is heterogeneous and largely observational. [These findings] should mainly be used to reassure patients after inadvertent early exposure, rather than to endorse continued use throughout pregnancy.

Contemporary OB/GYN: No significant associations were found for gestational diabetes, preterm birth, preeclampsia, or hypertensive disorders. How should clinicians communicate that null result to patients, given the high heterogeneity across the included studies?

Jasper: Clinicians have to balance reassurance with transparency when communicating these findings—first, reassurance in the fact that we did not see a signal of increased risk for these outcomes when we pooled published studies. Second, transparency. They should also frame the evidence in context. The existing studies we included were very different in who was included, why a GLP-1 was prescribed, which medication it was, the dosage used, the timing and duration of the exposure, and [even] how they measured the outcomes. So, the certainty is limited. Providers should tell their patients, “Based on the data we have, we don't see evidence that early exposure increases risk of pregnancy complications. However, research is still limited, so we'll continue our routine pregnancy care based on your individual factors.” No evidence of increased risk does not mean proof of no risk. However, it is meaningful that our large, pooled data didn't show consistent signals of harm.

Contemporary OB/GYN: The sensitivity analysis suggesting a potential protective effect against gestational diabetes is intriguing. How much clinical weight should that exploratory finding carry at this stage?

Jasper: At this stage, I would say very little weight. The protective effect is certainly interesting and definitely hypothesis generating, but additional research and sensitivity analysis would be useful for understanding how robust these findings really are, because the results could reflect residual confounding. For example, patients on the GLP-1s might systematically differ than those who aren't on them. There could be differences in pre-pregnancy BMI and baseline genetic or metabolic risk, and those could be contributing to the findings, too. We also observed differences in the timing and duration of exposure between studies, and these factors could influence the amount of weight that's lost. We know that weight is heavily tied to the risk of gestational diabetes, so future research needs to investigate this further before we can make definitive conclusions. I would not tell clinicians or patients that GLP-1s protect against gestational diabetes. I would say in a meta-analysis, the direction of effects suggests decreased risk but it’s still unclear if that's a medication effect or differences in underlying risk like BMI or pre-pregnancy metabolic health.

Contemporary OB/GYN: With over 47,000 exposed pregnancies included, this is a substantial sample size, yet the certainty of evidence remains limited by study quality variability. What would a more definitive study need to look like?

Jasper: Randomizing pregnant patients to GLP-1s is not ethical or feasible, so the best path forward is high-quality prospective registries, pregnancy registries, and maybe different study designs like target trial emulation, and then diverse, generalizable health care populations. A more definitive observational study would ideally have a couple features. The first, and most important, is clear exposure definition and timing including if it is preconception use vs perifertilization vs first trimester exposure, and the dose, the duration, and the specific agent. We also need a strong comparison group, so a group of individuals without that GLP-1 exposure that matches the clinical scenario—patients with similar BMI or diabetes risk who are using alternative therapies or those who discontinued the GLP-1s before conception vs those who had early exposure inadvertently. And then we need more information on several key confounders, like their baseline BMI, for the groups that lost weight, how much weight they lost, their A1C, other comorbidities, their parity is certainly important, and their prior history of these pregnancy complications, as well as concurrent medications and socioeconomic factors. And then, like I said, a pregnancy registry or a rigorously designed observational cohort using methods like propensity scores, active comparators, and sensitivity analysis would really help us provide a more precise estimate of relationships.

Contemporary OB/GYN: Current guidance generally recommends stopping GLP-1 receptor agonists before or upon recognition of pregnancy. How does this meta-analysis inform that recommendation?

Jasper: Our results support the current cautious guidance in two ways. First, there really isn't enough high-quality evidence to recommend intentional continued use throughout pregnancy, so stopping remains the most appropriate [option] when pregnancy is either planned or recognized. Second, it offers reassurance to providers and patients that if exposure happens around conception or early in pregnancy before you might even know you're pregnant, the available evidence does not show increased risk of maternal complications for the outcomes we were able to study. [I would recommend] continuing the clinical advice of discontinuation when planning a pregnancy or when a pregnancy is recognized, but to avoid alarmism after inadvertent exposure.

Contemporary OB/GYN: GLP-1 receptor agonists are prescribed across multiple specialties. How should ob-gyns coordinate with endocrinologists and primary care physicians when a patient on one of these agents presents pregnant?

Jasper: Ob-gyns shouldn't be managing this in isolation, especially if the medication was prescribed for diabetes. They need to connect with endocrinologists and potentially primary care providers to evaluate the reason or indication for prescription and prevent gaps in glycemic control when it's prescribed for diabetes, and to ensure their patients are getting consistent counseling across providers. I'd emphasize a coordinated plan, with the main focus being on coordinating that medication management. Ob-gyns need to confirm which GLP-1 [the patient is using]; the indication (whether it's for weight loss or diabetes); dosage; and the start and, if it's been discontinued, stop dates. The reason and the timing of exposure in relation to conception will be particularly important for ob-gyns managing coordinated care. If pregnant people are still on the medication, ob-gyns can follow current guidelines of stopping those medications, but they will need to coordinate alternatives for diabetes or medical management with other providers if they need.

Second, when screening for metabolic risk in pregnancy and planning interventions, ob-gyns should think about early screening for gestational diabetes and inadequate or excessive gestational weight gain in these individuals. They may also need to work with endocrinologists, primary care providers, or other providers like dietitians to provide additional counseling for gestational weight gain, or prepare and implement interventions like nutrition counseling or more guidance on weight gain.

And then the transition to postpartum care will be critical. Providers should work with each other and their patients to discuss restarting GLP-1s in the postpartum if that's desired, and then breastfeeding if they plan to breastfeed, as well as the plans for future conception and planning for medication in relation to the next pregnancy.

Contemporary OB/GYN: What should ob-gyns tell a patient who calls after discovering she was on a GLP-1 receptor agonist during early pregnancy and is worried about her risk of complications?

Jasper: What I tell the patient is the reassuring news is that when we combined all available data from research currently, we don't see an increased risk of several major pregnancy complications, including preeclampsia, hypertensive disorders of pregnancy, preterm birth, and gestational diabetes after this exposure. However, the studies aren't all the same and the evidence quality varies, so we should still take a cautious approach by stopping the medication once you know you're pregnant, and then continue the standard prenatal care and evaluating your personal risk factors.

Contemporary OB/GYN: The sensitivity analysis hinted at a possible protective effect against gestational diabetes. How do you explain a hypothesis-generating finding like that without overstating it to patients?

Jasper: I would say in previous research, the direction of effect suggested a lower risk of gestational diabetes. Because past studies were all very different, we can't say for certain that this is because of the medication or something else, like differences in underlying risk, especially with BMI and pre-pregnancy metabolic health. We need more research on GLP-1s in pregnant patients, although it is reassuring we aren't seeing increased risk in this large, pooled analysis with over 47,000 pregnancies.

Contemporary OB/GYN: How should the current evidence shape the counseling conversation about GLP-1 receptor agonist use in women who are planning a pregnancy?

Jasper: For those planning a pregnancy, I'd frame it as a risk-benefit [situation]. Current guidance recommends stopping a GLP-1 receptor agonist before conception, or if the pregnancy is unplanned, when it's recognized. [This is] largely because we don't have that high-quality pregnancy safety data, and these drugs weren't intended for use during pregnancy. Our meta-analysis provides reassurance for scenarios of an inadvertent exposure shortly before or after pregnancy starts, as we didn't find evidence of increased risk for several major maternal complications, though existing evidence is heterogeneous. Counseling should recommend planning ahead when possible if you want to get pregnant and coordinating with your clinicians on stopping GLP-1s and alternatives, if necessary, as well as optimizing your weight and metabolic health prior to conception, if possible. If exposure does happen, we can provide some reassurance and proceed with routine pregnancy care and monitoring after discontinuation.

REFERENCE

1. Hattler E, Schluter H, Greene C, Adgent MA, Sundermann AC, Jasper EA. Glucagon-like peptide-1 receptor agonists and risk of adverse maternal pregnancy outcomes: A systematic review and meta-analysis. Obstet Gynecol. 2026 Jul 2:10.1097/AOG.0000000000006363. doi:10.1097/AOG.0000000000006363