Periconceptional and early-pregnancy exposure to SGLT2 inhibitors and congenital malformations: a systematic review and meta-analysis.

In 30 seconds

This systematic review and random-effects meta-analysis assessed observational cohort evidence on preconception or early-pregnancy SGLT2 inhibitor exposure among women with type 2 diabetes. Three cohorts included 669 exposed pregnancies. Compared with insulin, exposure was not associated with major congenital malformations (RR 0.94, 95% CI 0.68-1.29) or cardiac malformations (RR 0.97, 95% CI 0.64-1.48). A Korean cohort reported an association between exposure during gestational weeks 4-10 and congenital heart defects, while the authors judged the overall evidence limited and imprecise.

Key findings

• Against insulin comparators, major congenital malformations had a pooled RR of 0.94 (95% CI 0.68-1.29).
• Against insulin comparators, cardiac malformations had a pooled RR of 0.97 (95% CI 0.64-1.48).
• Adding a preconception sulfonylurea comparator cohort yielded a major-malformation RR of 0.98 (95% CI 0.74-1.29).
• In one Korean cohort, exposure during gestational weeks 4-10 was associated with congenital heart defects (RR 2.79, 95% CI 1.16-7.06).

Why it matters

SGLT2 inhibitors may be continued inadvertently until pregnancy is recognized, so estimates of fetal risk are clinically relevant. The pooled findings do not show an increased overall risk of major or cardiac malformations, but low to very low certainty and imprecise estimates mean that a meaningful increase cannot be excluded. The timing-specific cardiac finding also warrants attention without establishing causality.

What to keep in mind

Evidence came from only three observational cohorts with few exposed events. The authors cite residual confounding, live-birth selection, and heterogeneous exposure definitions; certainty was low to very low.