Meta-analyzes find no clear rise in birth defects after GLP-1 exposure in pregnancy
Two new reviews found no clear rise in major birth defects after GLP-1 exposure in pregnancy, but the evidence is rated low-certainty and labels still say the drugs should not be used while pregnant.
Two meta-analyzes published in July 2026 found no statistically significant increase in major congenital malformations among pregnancies exposed to GLP-1 receptor agonists, but both groups of authors said the evidence is not strong enough to call the drugs safe during pregnancy [1][2].
The larger review, published in Scientific Reports, pooled seven cohort studies covering 42,282 GLP-1-exposed pregnancies and 723,892 comparison pregnancies [1]. The odds ratio for any congenital malformation was 1.11, with a 95 percent confidence interval of 0.82 to 1.51 [1]. Five studies that looked specifically at first-trimester exposure — 825 exposed pregnancies against 592,714 comparators — produced an odds ratio of 1.39 (95% CI, 0.73 to 2.65) [1]. A sensitivity analysis limited to four studies with adjusted estimates, covering 793 exposed and 488,871 comparator pregnancies, gave an odds ratio of 1.40 (95% CI, 0.63 to 3.12) [1]. For cardiac malformations specifically, three studies with 41,984 exposed and 136,485 comparator pregnancies found an odds ratio of 0.92 (95% CI, 0.67 to 1.27) [1].
One signal stood out in that review: urinary congenital malformations, with an odds ratio of 1.24 (95% CI, 1.05 to 1.47) across two studies covering 41,046 exposed and 131,407 comparator pregnancies [1]. Those estimates came only from unadjusted data, were driven largely by one large cohort, and no specific urinary malformation subtypes were reported, which the authors said limits any causal interpretation [1]. They added that the finding may reflect confounding by maternal diabetes or obesity rather than the medication itself [1].
Other outcomes in that review did not reach statistical significance. Stillbirth had an odds ratio of 2.17 (95% CI, 0.95 to 4.91), and the authors said a clinically meaningful increase could not be ruled out [1]. Spontaneous abortion was 0.95 (95% CI, 0.42 to 2.16), small-for-gestational-age births 0.84 (95% CI, 0.43 to 1.64), and preterm birth 1.17 (95% CI, 0.79 to 1.72), the last with substantial variation between studies [1].
The second review, in Endocrine Connections, searched literature through December 2025 and included one prospective and five retrospective studies totaling 286,599 women — 43,577 exposed to GLP-1 receptor agonists and 243,022 unexposed [2]. It reported a relative risk of 1.02 (95% CI, 0.96 to 1.08) for major congenital malformations [2]. Preterm birth was 1.09 (95% CI, 0.80 to 1.49), large-for-gestational-age 2.31 (95% CI, 0.56 to 9.44), small-for-gestational-age 0.71 (95% CI, 0.39 to 1.27), and stillbirth 1.16 (95% CI, 0.24 to 5.69) [2]. Spontaneous abortion rates were comparable between groups in one study [2].
The two reviews differ in search windows, numbers of studies and effect measures — one reports odds ratios, the other relative risks — so their figures are not directly comparable [1][2]. In the Scientific Reports review, semaglutide and liraglutide were the most frequently reported drugs, followed by exenatide and dulaglutide; tirzepatide appeared in only one included study, and individual drugs could not be analyzed separately [1].
Both papers rely on observational data. The Scientific Reports authors rated the certainty of evidence for their outcomes as low or very low, and noted that prescription records did not always confirm the medications were actually taken [1]. The Endocrine Connections authors wrote that their findings "should not be interpreted as proof of safety" [2].
Why it matters for patients
GLP-1 medications are increasingly prescribed to women of reproductive age, and the drugs can restore ovulation, so unplanned pregnancies during treatment are common [1]. That means many people learn they are pregnant while on a GLP-1 drug, or shortly after stopping one.
For those patients, these reviews offer limited reassurance rather than a green light. Neither found a statistically significant rise in major malformations overall, but both flagged weak data, and one review could not rule out a meaningful increase in stillbirth [1]. A separate urinary malformation signal remains unexplained and rests on unadjusted estimates [1].
Current guidance has not changed. The Endocrine Connections authors state that all GLP-1 receptor agonists are contraindicated during pregnancy and that discontinuation before a planned conception is recommended [2]. Studies in animals have shown embryonic growth retardation and skeletal malformations, findings that cannot be tested in human trials for ethical reasons [2]. Neither paper reports a regulatory change or new labeling guidance.
What happens next
Both groups called for larger population studies using standardized definitions of exposure, more detailed classification of outcomes, and better adjustment for factors such as maternal diabetes and obesity [1][2]. The Endocrine Connections authors also called for large prospective cohorts and randomized trials, while noting the ethical limits on testing these drugs in pregnancy [2]. No specific study start dates or completion dates were disclosed in either paper [1][2].
Sources
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