Dapagliflozin in Pregnancy
Direct Recommendation
Dapagliflozin is contraindicated in pregnancy and must be discontinued immediately upon conception or pregnancy recognition. Insulin is the only recommended pharmacologic agent for managing type 2 diabetes during pregnancy 1, 2, 3.
Evidence-Based Rationale
Why Dapagliflozin Cannot Be Used
Placental Transfer and Fetal Exposure:
- Recent ex vivo human placental perfusion studies demonstrate that dapagliflozin crosses the placental barrier, achieving a fetal-to-maternal concentration ratio of 0.67 ± 0.05 within 360 minutes 4.
- This substantial placental transfer results in direct fetal drug exposure, which poses unknown risks to the developing fetus 4.
Placental Hormone Disruption:
- Dapagliflozin causes a statistically significant decrease in placental leptin secretion, suggesting interference with normal placental endocrine function 4.
- The clinical implications of altered placental hormone production on fetal development remain unknown but are concerning 4.
Absence of Safety Data:
- No clinical trials have evaluated dapagliflozin safety or efficacy during pregnancy 4.
- The only human pregnancy data comes from ex vivo placental studies and one postpartum trial in women with prior gestational diabetes (not during pregnancy) 5.
Recommended Management Algorithm
For Women of Childbearing Age on Dapagliflozin:
Preconception Planning:
If Pregnancy Discovered While on Dapagliflozin:
Insulin Therapy Initiation:
Preferred insulin regimens during pregnancy include:
- Multiple daily injections using NPH insulin and rapid-acting insulin 2, 6.
- Continuous subcutaneous insulin infusion (insulin pump) 2, 6.
- Human insulin preparations (NPH, regular insulin) do not cross the placenta and are safe 2, 6.
Glycemic targets during pregnancy:
- Fasting glucose: 70-95 mg/dL 6.
- 1-hour postprandial: 110-140 mg/dL 6.
- 2-hour postprandial: 100-120 mg/dL 6.
- A1C target: <6% if achievable without significant hypoglycemia 3, 6.
Additional Pregnancy Management
Mandatory adjunctive therapy:
- Low-dose aspirin 100-150 mg daily starting at 12-16 weeks gestation to reduce preeclampsia risk 1, 3, 6.
Monitoring requirements:
- Baseline ophthalmology examination in first trimester with follow-up each trimester as indicated 3.
- Frequent blood glucose monitoring with insulin dose adjustments throughout pregnancy 6.
- Education on hypoglycemia prevention, recognition, and treatment for patient and family 2, 6.
Other medications to avoid:
Critical Clinical Pitfalls
Common errors to avoid:
- Do not continue dapagliflozin "just until the first prenatal visit"—stop immediately upon positive pregnancy test 1.
- Do not substitute metformin for dapagliflozin as a compromise; insulin is the preferred agent 1, 2.
- While metformin may be considered in specific circumstances (cost barriers, inability to use insulin safely), it should not be used in women with hypertension, preeclampsia, or risk for intrauterine growth restriction 1.
Insulin dosing considerations:
- Insulin requirements typically double during pregnancy compared to pre-pregnancy needs, with increases beginning around 16 weeks 2, 6.
- Type 2 diabetes often requires much higher insulin doses than type 1 diabetes, sometimes necessitating concentrated insulin formulations 3.
- Insulin requirements drop dramatically immediately after placental delivery 1, 2, 6.
Postpartum Considerations
After delivery: