Are sodium‑glucose cotransporter‑2 (SGLT‑2) inhibitors safe to use during pregnancy?

SGLT-2 Inhibitors Are Contraindicated During Pregnancy

SGLT-2 inhibitors should NOT be used during pregnancy and must be discontinued before conception, not after pregnancy is confirmed. 1

Key Recommendation

The 2025 Endocrine Society/European Society of Endocrinology joint guideline explicitly recommends discontinuing SGLT-2 inhibitors before conception rather than waiting until pregnancy is confirmed 1. This is a conditional recommendation based on limited safety data and the unknown effects of these medications on placental GLP-1 receptors and fetal development.

Why SGLT-2 Inhibitors Must Be Stopped

Placental Transfer and Fetal Exposure

• All SGLT-2 inhibitors cross the placenta within 4 hours at clinically relevant concentrations 2
• Dapagliflozin crosses fastest; empagliflozin slowest
• More lipophilic agents (canagliflozin, ertugliflozin) accumulate heavily in placental tissue 2
• Transfer occurs via passive diffusion, modulated by efflux transporters and protein binding 2

Potential Fetal Risks

Recent 2026 data shows concerning signals:

• Increased risk of congenital heart defects during organogenesis (gestational weeks 4-10) with a relative risk of 2.79 (95% CI: 1.16-7.06) 3
• While overall congenital malformation risk was not elevated in the full first trimester, the timing-specific risk during critical organ formation is significant 3
• Altered placental glycolytic activity, though without immediate impairment of viability or hormone secretion 2

Unknown Long-Term Effects

The guidelines emphasize critical knowledge gaps 1:

• Effects on fetal development and teratogenicity
• Impact on spontaneous abortion rates
• Fetal growth patterns
• Placental drug passage consequences
• Long-term childhood outcomes

Clinical Management Algorithm

For Women Planning Pregnancy:

1. Discontinue SGLT-2 inhibitors BEFORE attempting conception 1
2. Use effective contraception while on SGLT-2 inhibitors 1
3. Transition to insulin (preferred) or metformin for glycemic control
4. Ensure glucose is actively monitored during the transition 1

For Unplanned Pregnancy on SGLT-2 Inhibitors:

1. Discontinue immediately upon pregnancy confirmation
2. Transition urgently to insulin-based regimen
3. Implement intensive glucose monitoring
4. Counsel about the timing-specific risk if exposure occurred during weeks 4-10

Critical Pitfall to Avoid:

Do NOT wait until the end of the first trimester to discontinue 1. The organogenesis period (weeks 4-10) is when congenital heart defect risk appears elevated 3. Many women don't confirm pregnancy until 6-8 weeks, making preconception discontinuation essential.

Why This Matters More Than You Think

Approximately 40% of pregnancies remain unintended 1, and SGLT-2 inhibitors improve fertility 1, creating a perfect storm for inadvertent exposure. The 2026 case reports document accidental spontaneous conception within 7 months of starting combination GLP-1RA/SGLT-2i therapy 4.

Balancing Risks of Discontinuation

The guidelines acknowledge legitimate concerns about stopping SGLT-2 inhibitors 1:

• Risk of hyperglycemia rebound
• Potential weight regain
• Loss of achieved glycemic targets

However, these metabolic risks do not outweigh the uncertain but potentially serious fetal risks. The GDP (guideline development panel) explicitly prioritized "uncertainty of potential harms" to the fetus over maternal metabolic concerns 1.

What to Use Instead

Insulin remains the gold standard for diabetes management in pregnancy 1, 5. Metformin may be considered as adjunctive therapy in some cases, though the 2025 guidelines suggest against routine addition to insulin in T2DM pregnancy due to concerns about small-for-gestational-age infants and childhood metabolic effects 1.

Emerging Evidence Nuance

While the 2026 Korean cohort study 3 found no overall increased malformation risk with first-trimester SGLT-2 inhibitor exposure, the organogenesis-specific signal for cardiac defects cannot be dismissed. The study authors themselves emphasize "cautious interpretation" and note the importance of exposure timing 3. The 2026 placental transfer study confirms these agents readily cross to the fetus and alter placental metabolism 2, reinforcing that use during pregnancy "should remain contraindicated" 2.

Bottom line: SGLT-2 inhibitors must be stopped before conception, with effective contraception used until discontinuation, and immediate transition to pregnancy-safe alternatives with intensive glucose monitoring.