Impact of Preconception GLP-1RA and Dual GIP/GLP-1RA Use on Insulin Requirements During Pregnancy in Patients with Type 2 Diabetes Authors: Kiera Rountree, Jessica Odom, Autumn Clemins, and Megan Schellinger
Practice Site: Prisma Health-Upstate
Background Pregestational diabetes affect approximately 1–2% of pregnancies and is associated with increased maternal and neonatal morbidity. Achieving tight glycemic goals before and throughout pregnancy is essential to reduce the risk of congenital anomalies, abnormal fetal growth, hypertensive disorders, and delivery complications. Insulin requirements fluctuate during pregnancy due to physiologic changes in insulin sensitivity, with progressive insulin resistance typically emerging in the second and third trimesters. Insulin is the preferred treatment for diabetes in pregnancy; however, glucagon-like peptide-1 receptor agonists (GLP-1RA) and dual glucose-dependent insulinotropic polypeptide/GLP-1RA (GIP/GLP-1RA) are increasingly used in women of reproductive age for type 2 diabetes and obesity. Current guidelines recommend discontinuation of these agents prior to conception due to limited safety data, yet optimal timing of discontinuation remains unclear. Discontinuation may precipitate hyperglycemia requiring insulin initiation or escalation, and many pregnancies are unplanned, resulting in inadvertent early exposure. Data evaluating the impact of preconception GLP-1–based therapy on insulin requirements during pregnancy are lacking. This study aims to evaluate whether preconception exposure to GLP-1RA or dual GIP/GLP-1RA affects insulin requirements during pregnancy in patients with preexisting type 2 diabetes.
Methods This single-center, observational, retrospective cohort study included pregnant patients with preexisting type 2 diabetes enrolled in the Management of Maternal Diabetes (MOMs) program at Prisma Health Upstate between June 2023 and March 2025. Eligible patients were ≥18 years old with singleton pregnancies and documented GLP-1RA or dual GIP/GLP-1RA use within 60 days prior to conception, discontinued before or during early pregnancy. A comparator group without GLP-1–based therapy exposure was identified. Patients with gestational or type 1 diabetes, multiple gestations, insulin pump use, or incomplete insulin data were excluded. The primary outcome was the change in total daily insulin dose (units/kg/day) from baseline intake visit to the third trimester visit closest to delivery. Secondary outcomes included change in hemoglobin A1c, weight change, initiation and use of continuous glucose monitor (CGM), and maternal and neonatal outcomes. Data was collected through manual chart review, existing REDCap registry of MOMS participants, and pharmacy dispensing records. Statistical analyses were conducted with support from a statistician.
Results 64 pregnant patients with type 2 diabetes were included; 13 (20.3%) had preconception GLP-1 receptor agonist exposure. Mean age (31.6 ± 6.2 years) and baseline BMI (37.4 ± 8.3 kg/m²) were similar between groups. Patients with preconception GLP-1 use were more likely to have hypertension (69.2% vs 31.4%, p=0.02) and obesity (76.9% vs 35.3%, p=0.01). Median total daily insulin dose increased from baseline to the third trimester from 0.3 (0.3–0.7) to 1.1 (0.8–1.5) units/kg/day. Patients with preconception GLP-1 exposure had higher insulin requirements at baseline (0.7 vs 0.3 units/kg/day, p=0.04) and in the third trimester (1.35 vs 1.0 units/kg/day, p=0.05). Hemoglobin A1c improved during pregnancy from 8.6 ± 2.0% to 6.4 ± 0.8%, with no differences between groups. A trend toward greater weight gain was observed in the preconception GLP-1 group (median 10 vs. 6 kg, p = 0.07), though not statistically significant. CGM use increased during pregnancy, with 43.8% of patients initiating CGM, and did not differ by exposure group. Maternal and neonatal outcomes were similar between groups; however, postpartum hemorrhage (15.4% vs 0%, p=0.04) and other major maternal complications (15.4% vs 0%, p=0.04) occurred more frequently in the preconception GLP-1 group. Neonatal complications were not significantly different.
Conclusion Preconception GLP-1-RA or dual GIP/GLP-1RA use was associated with higher insulin requirements throughout pregnancy, suggesting greater baseline insulin resistance. Glycemic targets and maternal and neonatal outcomes were similar, though greater weight gain was observed. These findings support early anticipation of increased insulin requirements, with proactive monitoring and timely dose titration to maintain glycemic targets.
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