When should GLP-1 (Glucagon-like peptide-1) receptor agonists, SGLT2 (Sodium-glucose cotransporter 2) inhibitors, and DPP4 (Dipeptidyl peptidase-4) inhibitors be stopped in a pregnant woman with diabetes?

When to Stop GLP-1 Receptor Agonists, SGLT2 Inhibitors, and DPP-4 Inhibitors in Pregnancy

GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors must be discontinued immediately upon pregnancy confirmation or as soon as the patient becomes aware of pregnancy. 1, 2

Timing of Discontinuation

GLP-1 Receptor Agonists

• Stop immediately upon pregnancy confirmation - these medications should be discontinued as soon as the patient becomes aware of pregnancy 2
• Current evidence shows GLP-1 agonists are not approved for use during pregnancy, and while the incidence of congenital abnormalities appears relatively low from inadvertent exposures, planned use is not recommended 2
• Animal studies demonstrate reduced fetal weight, delayed ossification, and skeletal variants, though human placental transfer appears minimal 3
• A single case report of first-trimester liraglutide exposure resulted in normal pregnancy outcome, but this does not establish safety 4

SGLT2 Inhibitors

• Stop immediately upon pregnancy confirmation - discontinue as soon as pregnancy is detected 1
• Animal studies show renal toxicity during periods corresponding to late second and third trimester human renal development, including renal pelvis and tubular dilatation 3
• Human pharmaceutical database data suggest increased miscarriages and congenital malformations with inadvertent exposure 3
• Recent multinational cohort data (2024) showed no large increased risk of major congenital malformations above baseline T2D risk, but confirmation from additional studies is needed 5

DPP-4 Inhibitors

• Stop immediately upon pregnancy confirmation - discontinue when pregnancy is detected 1
• Limited human safety data exist, though a 2024 multinational study showed adjusted relative risk of 0.83 (95% CI, 0.64-1.06) for major congenital malformations compared to insulin, suggesting no increased risk 5
• Despite reassuring preliminary data, continuous monitoring is needed as evidence accumulates 5

Medication Substitutions Upon Pregnancy Confirmation

First-Line Therapy

• Insulin should be initiated or optimized as first-line therapy for all women with preexisting diabetes in pregnancy 1
• Insulin requirements are typically roughly half the prepregnancy requirements for the initial few days postpartum 6

Acceptable Oral Agents (If Already in Use)

• Metformin may be continued throughout pregnancy if already in use, as it does not increase fetal anomalies and may reduce neonatal hypoglycemia and maternal weight gain 1
• Glyburide may be continued alongside insulin if already in use, but must be discontinued at least two weeks before expected delivery date due to risk of prolonged neonatal hypoglycemia 1

Critical Implementation Points

Preconception Planning

• All women with diabetes of childbearing potential should have contraception counseling at regular intervals until medications are optimized and glycemic goals achieved (A1C <6.5%, ideally <6%) 1
• Medication review must occur immediately upon pregnancy confirmation to minimize teratogenic exposure 1

Additional Medications to Stop

• ACE inhibitors and ARBs must be stopped prior to conception and avoided in sexually active individuals of childbearing potential not using reliable contraception to prevent fetal renal dysplasia, oligohydramnios, pulmonary hypoplasia, intrauterine growth restriction, and fetal death 6, 1
• Statins must be discontinued at the first pregnancy visit as they are pregnancy category X and contraindicated 1
• Atenolol should be stopped due to association with fetal growth restriction and lower birth weight 1

Antihypertensive Substitutions

• Methyldopa, labetalol, and long-acting nifedipine are recommended as first-line options for blood pressure control 1
• Target blood pressure should be 110-135/85 mmHg to balance maternal hypertension risk against fetal growth impairment 6, 1

Additional Medications to Initiate

• Low-dose aspirin (100-150 mg daily) should be started at 12-16 weeks gestation to reduce preeclampsia risk in women with type 1 or type 2 diabetes 6, 1

Common Pitfalls to Avoid

• Failing to discontinue newer antidiabetic agents immediately - the rapid uptake of GLP-1 agonists and SGLT2 inhibitors for diabetes and obesity treatment has resulted in increasing inadvertent pregnancy exposures 3, 5
• Delaying insulin initiation - insulin remains the gold standard for glycemic control in pregnancy and should be started promptly upon discontinuation of contraindicated agents 1
• Inadequate preconception counseling - the majority of pregnancies are unplanned, making proactive contraception counseling essential for all women with diabetes of childbearing potential 6