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This two-phased study consists of a decision tree model built from real-world claims data to determine factors related to physician choice of 2nd line therapy for type 2 diabetes (T2D) patients after metformin, followed by a physician focus group study to validate results of the data-driven approach. We identified 58patients in the U.S. who initiated sulfonylurea (SU), DPP-4 inhibitor, GLP-1-RA, or insulin after metformin during 2012-2014 from the HealthCore Integrated Research Database. Claims-derived factors, such as demographics, clinical characteristics, and prior healthcare utilization and costs, were selected from a classification and regression tree (CART) model that minimized classification errors. Of factors most predictive of 2nd line drug assignment, patients’ cost sharing for antidiabetic drugs (Relative Importance, RI=1) was 3 times more important than HbA1c level (RI=0.3), and 10 times more important than age, comorbidity, and kidney status (GFR) (RI=0.1). SU was most likely to be assigned to patients with lowest drug spending, moderate HbA1c control, abnormal kidney function, or no comorbid conditions. Similar themes were identified from the four physician focus groups (consisting of 8 endocrinologists and 10 PCPs in NYC and LA) and supported the findings. This study identified a gap in diabetes care where patients often receive SU due to lack of access to other treatment options. Disclosure S. Wu: None. A.D. Raval: None. J.J. Stephenson: None. X. Peng: Employee; Self; Eli Lilly and Company. H. Weisman: Employee; Self; Anthem, Inc. D.E. Faries: Employee; Self; Eli Lilly and Company.

Background Newer oral antidiabetic drug classes are expanding treatment options for type 2 diabetes mellitus (T2DM); however, concerns remain. The objective was to assess relative risk of heart failure hospitalization of sodium–glucose co-transporter-2 (SGLT2) and dipeptidyl peptidase-4 (DPP4) inhibitors in T2DM patients. Methods This retrospective observational study used a national commercially insured claims database. Adults (>18 years) with T2DM newly starting SGLT2 or DPP4 medication between April 2013 and December 2014 were included. Depending on their index fill, patients were grouped into either SGLT2 or DPP4 medication class cohorts. The primary outcome was hospitalization for heart failure and the risk was assessed using Cox regression models. Propensity score matching (1:2 ratio) was used to adjust for potential confounders. Analyses were also stratified by the presence of baseline diabetes complication and age (

Insulin release from the pancreas in response to glucose appears at the end of gestation in the fetal rat and develops completely in the neonatal period. To determine when this response begins to occur in fetal pancreases transplanted into adult animals, in vitro perfusions were performed in normal and diabetic rats after varying periods of growth. Responsivity to a 300 mg/dl glucose as opposed to a basal medium (50 mg/dl) was not present in the transplanted organ after 3 or 5 wk of growth in normal rats, despite a rise in total insulin content from 88 ± 10 mU to 197 ± 10 mU per two pancreases. Transfer of the pancreases—after 3 wk in the normal—to a diabetic rat for 2 wk resulted in a greater insulin content (343 ± 15 mU) and more insulin being released during perfusion with the basal medium (1863 ± 56 vs. 1374 ± 113 μU/h). Insulin release from these pancreases doubled during perfusion with the high glucose medium rather than with the basal medium. When the transplanted pancreas was left in the normal rats for 5 wk before being transferred to the diabetic animal for 2 wk, the insulin content increased (450 ±10 mU) but there was no response to the glucose challenge during perfusion, despite good function, indicated by a response of all transplanted animals in the diabetic state. We conclude that glucose-induced insulin release will develop in the fetal rat pancreas transplanted into an adult animal after exposure to hyperglycemia, but optimal function requires a period of prior normoglycemia. Careful control of blood glucose with insulin may provide these conditions and will be required when this method is applied to diabetic patients.

Despite the best efforts of physicians and diabetic patients in the use of insulin for control of juvenile-onset (insulin-deficient) diabetes, vascular complications occur in most patients...