SGLT-2 Inhibitors Should NOT Be Started During Active Infertility Treatment
SGLT-2 inhibitors must be discontinued before attempting conception and are contraindicated during pregnancy and breastfeeding. 1 While these medications offer substantial cardiovascular and renal benefits in type 2 diabetes, their use during infertility treatment poses unacceptable risks due to lack of safety data in pregnancy and the potential for inadvertent fetal exposure.
Clinical Decision Framework
Absolute Contraindications for SGLT-2 Inhibitor Use:
The Timing Problem
When patients with type 2 diabetes are undergoing infertility treatment, conception can occur unpredictably—often before pregnancy is confirmed. A recent case series 2 documented two women with PCOS and newly diagnosed type 2 diabetes who conceived "accidentally" within 7 months of starting combined GLP-1 RA and SGLT-2 inhibitor therapy. While both pregnancies resulted in healthy births after immediate medication discontinuation, this highlights the critical window of inadvertent early pregnancy exposure that cannot be reliably prevented.
Why This Matters for Morbidity and Mortality
The guidelines are unequivocal: there are no safety data available for SGLT-2 inhibitors in pregnancy 1. While preliminary emerging studies suggest no major teratogenic concerns from early inadvertent exposure 2, robust safety profiles regarding embryotoxicity have not been established. The clinical standard remains immediate discontinuation and transition to metformin and/or insulin prior to planning pregnancy 2.
Recommended Management Algorithm
For Patients Planning Infertility Treatment:
- Stop SGLT-2 inhibitor immediately when infertility treatment is planned
- Transition to pregnancy-safe alternatives:
- Metformin (first-line for glycemic control)
- Insulin (as needed for glycemic targets)
- Optimize glycemic control before conception (target A1C <6.5% if achievable without hypoglycemia)
- Consider restarting SGLT-2 inhibitor only after:
- Completion of breastfeeding
- No plans for future pregnancies in the near term
For Patients Already on SGLT-2 Inhibitors:
If a patient becomes pregnant while on an SGLT-2 inhibitor:
- Discontinue immediately upon pregnancy confirmation 2
- Transition to insulin ± metformin
- Provide reassurance that inadvertent early exposure appears to have low teratogenic risk based on limited data 2
Important Caveats
The cardiovascular and renal benefits of SGLT-2 inhibitors are substantial 3, 4, 5—including reduced mortality, heart failure hospitalization, and kidney disease progression. However, these long-term benefits cannot justify use during the high-risk window of potential conception and early pregnancy when safety data are absent.
For women with PCOS and type 2 diabetes, the combination of weight loss medications (including SGLT-2 inhibitors) may actually restore fertility more rapidly than anticipated 2, making inadvertent conception more likely—another reason to avoid these agents during infertility treatment.
After delivery and completion of breastfeeding, strongly consider reinitiating SGLT-2 inhibitor therapy, particularly if the patient has:
- Albuminuria (ACR ≥200 mg/g) 4, 5
- eGFR 20-90 mL/min/1.73 m² 4, 5
- Heart failure 3
- Established cardiovascular disease 1
The proven mortality and morbidity benefits in these populations make SGLT-2 inhibitors essential therapy once pregnancy and breastfeeding are no longer considerations.