Abstract Body (Do not enter title and authors here): Objective: Though updated American Diabetes Association (ADA) guidelines recommend initiating GLP1 receptor agonists (GLP1) or SGLT2 inhibitors (SGLT2i) for persons with type 2 diabetes mellitus (PWT2DM) with high CV risk, metformin was previously recommended as 1st-line treatment. For PWT2DM at moderate CV risk, it is unknown which 2nd-line drug optimizes CV outcomes. Our multicenter observational study describes US-wide trends in 2nd-line T2DM medication use (DPP4 inhibitors [DPP4i], GLP1s, SGLT2i and sulfonylureas [SU]) overall and in key sociodemographic subgroups between 2014-2023.

Methods: This is a secondary analysis of the oBservational Evaluation of Second line Therapy Medications in Diabetes (BESTMED) study, which used a new-user design to evaluate associations between 2nd-line medications and CV events in PWT2DM at moderate CV risk. The database comprised EHRs and insurance claims for 75,224 PWT2DM from 10 health systems and 2 insurance plans on metformin who initiated a 2nd medication from 1/2013 to 1/2023. Data were obtained from orders or prescription fills. Prescription class was regressed on calendar time via multinomial logistic regression to model trends in prescribing patterns, adjusted for sociodemographic variables. Subgroup analyses were performed by adjustment factors; CIs and p-values for differences were calculated via nonparametric bootstrap (B=200). Due to large sample size, statistical significance was interpreted at p<0.05 and annual rate of change >0.5%.

Results: We included 75,224 T2DM adults (median A1c 7.8%), of whom 18%,17%, 18%, and 47% initiated DPP4i, GLP1, SGLT2i, SU respectively. From 2014 - 2023, SGLT2i and GLP1 increased: 5.7 to 28.8%, and 3.5 to 30.3%, and DPP4i and SUs decreased: 25.3 to 11.6%, and 65.6 to 29.3%, respectively. Annual rate of change for SGLT2i was higher in men(3.0% vs 2.1%/year; p<0.001) and in >65 y (3.0% vs 2.4%; p<0.001), and for GLP1s was higher in those <65 y (3.6% vs 2.1%; p<0.001), women (3.5% vs 2.5%; p<0.001), Hispanic ethnicity (3.2% vs 2.7%; p=0.005), and with class II/III obesity (4.1% versus 2.6% per year; p<0.001). There was no evidence that these trends differed by race, insurance, or SDI.

Conclusion:In this nationwide study of prescribing patterns PWT2DM at moderate CV risk, prevalences of 2nd-line T2DM therapies are approaching current ADA guidelines for initial therapy for those at high CV risk. Differences between sociodemographic groups appear aligned with clinical expectations.