SGLT2 inhibitors in early pregnancy: no overall malformation signal, but the data are thin

Design

Systematic review and meta-analysis of observational cohorts

Population

3 cohorts, 669 SGLT2 inhibitor-exposed pregnancies in women with type 2 diabetes

Primary outcome

Major congenital malformations

Effect

RR 0.94 (0.68–1.29) vs insulin; cardiac malformations RR 0.97 (0.64–1.48)

SGLT2 inhibitors are now prescribed to many women of reproductive age for diabetes, heart failure and kidney protection, and are often still being taken when pregnancy is discovered. This meta-analysis, by an Indian-led group, pooled three observational cohorts with 669 exposed pregnancies, comparing early SGLT2 inhibitor exposure with other glucose-lowering drugs in women with type 2 diabetes.

Against insulin, early exposure was not associated with major congenital malformations (RR 0.94, 95% CI 0.68–1.29) or cardiac malformations (RR 0.97, 0.64–1.48). Adding a sulfonylurea comparator gave a similar result. One Korean cohort, however, found exposure in gestational weeks 4–10 associated with congenital heart defects (RR 2.79, 1.16–7.06).

The authors rate certainty low to very low. The intervals are wide enough to include a meaningful increase in risk, and live-birth-only data miss malformations ending in pregnancy loss. This is reassurance for counselling after inadvertent exposure, not permission to continue the drug in pregnancy.

• Ask about pregnancy plans when starting an SGLT2 inhibitor in a woman of reproductive age, and discuss contraception.
• Stop the SGLT2 inhibitor once pregnancy is recognised; product labelling does not support use in pregnancy.
• After inadvertent early exposure, the available data do not show a clear rise in overall malformations, which can help counselling.
• Consider a detailed fetal anomaly scan, including the heart, after exposure in early pregnancy, given the single-cohort cardiac signal.

Why it matters

Cardiologists now start these drugs in younger women for heart failure, so the pregnancy conversation has moved into cardiology clinic.

Don't overread it

Three small observational cohorts cannot show SGLT2 inhibitors are safe in pregnancy.

The statistics, in plain English

A relative risk near 1.0 means no difference on average, but the confidence interval runs up to 1.29 for any major malformation and 1.48 for cardiac defects, so an increase of that size cannot be excluded. The one positive cardiac signal came from a single cohort and a narrow exposure window, which makes it a lead to check, not a finding.

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