Preconception liraglutide exposure leads to weight regain but does not worsen pregnancy outcomes after discontinuation

The rising prevalence of obesity in reproductive-aged women increases risks for cardiometabolic diseases and pregnancy complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), like liraglutide, are increasingly used for obesity and type 2 diabetes, yet their long-term impact, especially regarding preconception exposure and subsequent pregnancy outcomes, remains poorly understood. Current data on GLP-1RA exposure prior to pregnancy and its effects on maternal and fetal health are mixed, creating a critical knowledge gap for clinicians and patients.

This retrospective study evaluated bodyweight and pregnancy outcomes in 556 women of reproductive age who started liraglutide for obesity management, with 2-5 years of follow-up. Researchers compared pregnancies occurring in the same women before and after preconception liraglutide exposure, which was discontinued prior to conception. Primary endpoints included weight change, gestational weight gain, and various pregnancy-related complications such as gestational diabetes and preterm delivery.

Of the 556 women included, 97 (17.4%) conceived after liraglutide exposure, while 459 (82.6%) did not. After 2-5 years, women who conceived experienced a mean final weight change of +1.1 ± 11.3%, significantly different from the -6.7 ± 9.9% weight reduction observed in non-conceiving women (p < 0.001). The nadir weight reduction on liraglutide in women who conceived was -6.2 ± 7.8%. Importantly, gestational weight change was similar between pre- and post-exposure pregnancies (8.0 ± 10.9% vs. 9.2 ± 11.8%, p = 0.554). > There were no significant differences in key pregnancy outcomes: gestational diabetes (32.1% vs. 37.7%, p = 0.629), hypertensive disorders of pregnancy (9.2% vs. 0%, p = 0.063), need for c-section (33.3% vs. 38.9%, p = 0.549), pre-term delivery (3.7% vs. 1.9%, p = 0.500), large for gestational age (5.5% vs. 5.5%, p = 1), or small for gestational age infants (11.1% vs. 9.3%, p = 1) in pre- vs. post-exposure pregnancies. A subgroup analysis showed a non-significant trend towards lower gestational weight gain with metformin use during pregnancy (5.8 ± 9.1 kg vs. 8.2 ± 9.5 kg, p = 0.369).