Sodium Glucose Co-Transporter 2 Inhibitor Exposure and the Risk of Congenital Malformations: Nationwide Birth Cohort Study
Author(s)
Minseol Jang, PharmD1, Miryoung Kim, RPh, MCP, PhD1, Hae Sun Suh, RPh, MPharm, MA, PhD2;
1Kyung Hee University, Department of Regulatory Science, Graduate School, Seoul, Korea, Republic of, 2Kyung Hee University, College of Pharmacy, Seoul, Korea, Republic of
1Kyung Hee University, Department of Regulatory Science, Graduate School, Seoul, Korea, Republic of, 2Kyung Hee University, College of Pharmacy, Seoul, Korea, Republic of
Presentation Documents
OBJECTIVES: Diabetes is a common condition in pregnancy, and uncontrolled glucose levels are associated with an increased risk of malformations in offspring. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, a second-line option for type 2 diabetes, provide additional cardioprotective and renoprotective benefits. This study aimed to evaluate the association between SGLT2 inhibitor exposure during pregnancy and the risk of congenital malformations.
METHODS: This population-based cohort study utilized data from the National Health Insurance Service Database of South Korea (2016-2022). A total of 534,915 pregnancies among women with live-born infants between 2018 and 2021, aged 19 to 44 years and were included. Pregnancies with known teratogen exposure were excluded. SGLT2 inhibitor or insulin (as active comparator) use during the first trimester was defined as exposure. The primary outcomes were congenital malformations and heart defects. Propensity score matching controlled for confounders, and generalized linear regression estimated relative risks (RRs) with 95% confidence intervals (CIs). Negative control outcomes were employed to assess residual confounding.
RESULTS: Among 534,915 pregnancies, 142 pregnancies were exposed to SGLT2 inhibitors (mean [SD] age: 35.36 [4.11]), and 1,839 to insulin (mean [SD] age: 34.94 [4.28]). Among offspring exposed to SGLT2 inhibitors, 31 (21.8%) had major congenital malformations, and 27 (19.0%) had heart defects, compared to 392 (21.3%) and 292 (15.9%), respectively, in the insulin-exposed group. Adjusted RRs (95% CIs) for congenital malformations and heart defects were 0.95 (0.61-1.49) and 1.17 (0.69-2.00), respectively. No residual confounding detected in negative control outcome.
CONCLUSIONS: In this study, SGLT2 inhibitor use during the first trimester was not associated with an increased risk of congenital malformations. These findings provide evidence to guide clinical decision-making regarding antidiabetic medication use during pregnancy. Further research with greater sample sizes and expanded outcome measures is needed to ensure its safety.
METHODS: This population-based cohort study utilized data from the National Health Insurance Service Database of South Korea (2016-2022). A total of 534,915 pregnancies among women with live-born infants between 2018 and 2021, aged 19 to 44 years and were included. Pregnancies with known teratogen exposure were excluded. SGLT2 inhibitor or insulin (as active comparator) use during the first trimester was defined as exposure. The primary outcomes were congenital malformations and heart defects. Propensity score matching controlled for confounders, and generalized linear regression estimated relative risks (RRs) with 95% confidence intervals (CIs). Negative control outcomes were employed to assess residual confounding.
RESULTS: Among 534,915 pregnancies, 142 pregnancies were exposed to SGLT2 inhibitors (mean [SD] age: 35.36 [4.11]), and 1,839 to insulin (mean [SD] age: 34.94 [4.28]). Among offspring exposed to SGLT2 inhibitors, 31 (21.8%) had major congenital malformations, and 27 (19.0%) had heart defects, compared to 392 (21.3%) and 292 (15.9%), respectively, in the insulin-exposed group. Adjusted RRs (95% CIs) for congenital malformations and heart defects were 0.95 (0.61-1.49) and 1.17 (0.69-2.00), respectively. No residual confounding detected in negative control outcome.
CONCLUSIONS: In this study, SGLT2 inhibitor use during the first trimester was not associated with an increased risk of congenital malformations. These findings provide evidence to guide clinical decision-making regarding antidiabetic medication use during pregnancy. Further research with greater sample sizes and expanded outcome measures is needed to ensure its safety.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
EPH24
Topic
Epidemiology & Public Health
Topic Subcategory
Public Health, Safety & Pharmacoepidemiology
Disease
SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity), SDC: Pediatrics, SDC: Reproductive & Sexual Health