2138-P: A Novel Strategy for Optimizing Preconception Medication Choices in Women with Early-Onset Type 2 Diabetes

Introduction and Objective: Women with type 2 diabetes have suboptimal pregnancy outcomes, including high risks of miscarriage, stillbirth and perinatal death. Optimizing pre-pregnancy glycemia to achieve HbA1c <48 mmol/mol (6.5%) can improve outcomes. Insulin therapy preconception is widely recommended, but can cause weight gain and is often unappealing to patients, suggesting that alternative glucose-lowering agents may have a role. We aimed to identify optimal alternative therapies to improve glycemic control in women with early onset type 2 diabetes using a recently validated model which predicts individual glycemic responses to five major glucose-lowering drug classes using routine clinical features. Methods: We analyzed UK routine primary care data (Clinical Practice Research Datalink) for adult women 18-40 years old initiating one of 5 major glucose-lowering therapies post 1st-line metformin, up to December 2023. We excluded patients already treated with insulin. We assessed the model’s calibration of overall benefit drug pair comparisons in model-concordant and model-discordant patients. Results: We identified 6,533 therapy initiations (mean [SD] baseline characteristics: HbA1c 76[14] mmol/mol, age 35[4] years, BMI 37[9] kg/m2, diabetes duration 5[4] years and 66%, 24% and 6% self-identified as White, South Asian and Black ethnicities). Mean observed HbA1c reductions with initiation of SGLT2i, GLP-1RA, DPP4i, SU and TZDs were 13[17], 9[15], 3[16], 8[17] and 10[17] mmol/mol, respectively. Using the 5-drug class model, the best single agent was predicted to be SGLT2i in 61% and GLP-1RA in 32% of cases. Receiving model predicted optimal therapy was associated with a mean overall benefit of 5.7 (95% CI 4.6-7.0) mmol/mol, and model predictions were well-calibrated with observed responses. Conclusion: Optimal alternative treatments for women with early onset type 2 diabetes are SGLT2i or GLP1RAs to optimize glycemia in preparation for pregnancy. SGLT2is and GLP1RAs should be stopped 4-8 weeks before discontinuing contraception. Disclosure C. Meek: Research Support; Current; Dexcom, Inc. P. Cardoso: None. L. Kusinski: None. K.G. Young: None. A. Jones: None. E. Pearson: None. B. Shields: None. J. Dennis: None. Funding Diabetes UK project grant number 24/0006695. European Foundation for the Study of Diabetes - Novo Nordisk Foundation Future Leaders’ Award (NNF19SA058974).