Preconception SGLT2 or DPP4 inhibitor use and adverse pregnancy outcomes

Aims: To compare preconception use of sodium-glucose cotransporter-2 (SGLT2i) and dipeptidyl peptidase-4 (DPP4i) inhibitors to sulfonylurea agents, and associated peri-conceptional A1c concentration, and risk of pregnancy loss and congenital anomalies. Methods: This population-based cohort study used administrative datasets for all of Ontario, Canada, and included women eligible for free medication coverage and who achieved a recognized pregnancy from April 2007-November 2021. Exposure was a SGLT2i, DPP4i or sulfonylurea (referent) dispensed at least 90 days preconception. Study outcomes included differences in periconceptional A1c; miscarriage, induced abortion, or stillbirth; and any congenital anomaly - the latter two outcomes assessed using propensity score overlap weighting. Results: The mean (SD) periconceptional A1c was 8.1 % (2.0) among those prescribed any sulfonylurea, compared with 8.3 % (2.0) with a DPP4i and 7.8 % (1.6) with any SGLT2i. The risk of pregnancy loss was lowest among those exclusively prescribed a SGLT2i (relative risk [RR] 0.51, 95 % CI 0.22 to 0.91). Risk of a congenital anomaly at birth did not differ significantly comparing DPP4i or SGLT2i to sulfonylurea agents. Conclusions: Neither SGLT2i nor DPP4i use before pregnancy was associated with a difference in A1c, or a higher risk of selective adverse outcomes, compared to sulfonylureas. Future larger studies are required, including assessment of medication use after conception, during the critical period of embryogenesis.