GLP-1 Receptor Agonists Should NOT Be Used in Non-Diabetic Patients to Prevent Gestational Diabetes
GLP-1 receptor agonists are contraindicated in pregnancy and should not be used in non-diabetic patients attempting to prevent gestational diabetes mellitus (GDM). There is insufficient evidence to support their use for GDM prevention, and current guidelines do not recommend these medications during pregnancy or the preconception period for this indication.
Current Guideline Recommendations
The established approach to GDM management does not include GLP-1 receptor agonists:
Medical nutrition therapy (MNT) remains the cornerstone of GDM treatment, with insulin as the primary pharmacologic intervention when dietary measures fail to achieve glycemic targets 1.
For oral agents in established GDM, only glyburide has demonstrated minimal placental transfer (4% ex vivo) and acceptable safety data from randomized controlled trials, though it may be less effective in obese patients 1.
Metformin crosses the placenta, and guidelines from 2007 stated there was no evidence to recommend metformin for GDM except in clinical trials requiring long-term infant follow-up 1.
Notably, GLP-1 receptor agonists are not mentioned in established GDM treatment guidelines, reflecting the absence of evidence supporting their use 1.
Safety Concerns in Pregnancy
Multiple lines of evidence raise significant safety concerns:
Animal studies have demonstrated adverse outcomes including decreased fetal growth, skeletal and visceral anomalies, and embryonic death with GLP-1 receptor agonist exposure 2.
Current human data are limited to case reports and small observational studies, which are insufficient to establish safety 3, 2.
A 2025 review concluded that patients should be counseled there is not enough evidence to predict adverse effects or lack thereof from periconceptional GLP-1 receptor agonist exposure, and recommended all patients use contraception while taking these medications 2.
A recommended 4-week washout period prior to attempting conception has been suggested based on limited available literature 3.
Lack of Evidence for GDM Prevention
The evidence base does not support using GLP-1 receptor agonists to prevent GDM:
A 2020 systematic review examining DPP-4 inhibitors and GLP-1 receptor agonists in GDM found only 4 trials with 516 participants, and concluded that present data could not prove their use in GDM 4.
There are no prospective studies demonstrating that GLP-1 receptor agonist use prior to pregnancy improves pregnancy outcomes 5.
A 2025 narrative review stated there is currently insufficient evidence to demonstrate that GLP-1 receptor agonists prior to pregnancy improve pregnancy outcomes 5.
Clinical Implications
For non-diabetic patients concerned about GDM risk:
Focus on evidence-based preconception interventions: weight management through diet and exercise, achieving healthy BMI before conception 5.
If a patient is taking GLP-1 receptor agonists for weight loss and planning pregnancy, discontinue the medication with at least a 4-week washout period and implement effective contraception during treatment 3, 2.
For patients who conceive while on GLP-1 receptor agonists, discontinue immediately and provide counseling that current evidence cannot definitively predict outcomes 2.
Important Caveats
While GLP-1 receptor agonists have proven cardiovascular and metabolic benefits in non-pregnant adults with diabetes and obesity 1, these benefits do not extend to pregnancy or GDM prevention.
The gastrointestinal side effects (nausea, vomiting, delayed gastric emptying) are particularly problematic in pregnancy 1, 6.
Any future use would require prospective trials specifically designed to evaluate pregnancy and neonatal outcomes, which do not currently exist 3, 2.