Type 2 diabetes mellitus (T2D) is a common chronic disease associated with morbid and costly complications, including cardiovascular disease and chronic kidney disease - together referred to as cardiorenal complications. New medication classes - glucagon-like peptide-1 receptor agonists (GLP1 RA) and sodium-glucose cotransporter-2 inhibitors (SGL T2i) - have proven cardiorenal benefits in individuals with T2D. Veterans have a higher prevalence of T2D than the general population of US adults, and Veterans with T2D have a higher prevalence of cardiorenal complications than non-Veterans with T2D. Thus, evidence in Veterans with T2D regarding the effects of GLP1 RA, SGL T2i, and alternative glucose-lowering medications on glycemia and cardiorenal complications may have substantial implications for VA T2D care. However, Veterans are infrequently participants in influential randomized clinical trials (RCTs) of T2D medications, creating a critical evidence gap: whether the results of RCTs of GLP1 RA, SGL T2i, and other glucose-lowering medications are externally valid in Veterans with T2D. The overall goal of the proposed study is to use biostatistical tools known as transportability methods to project effects from recent RCTs of T2D treatment to Veterans with T2D and to evaluate the impacts of different treatment policies on cardiorenal complications in Veterans and system-wide costs. The challenge of assuming RCT results apply to potential real-world users of a medication who were not RCT participants is that differences in baseline characteristics could modify the treatment effect observed in the trial, leading to invalid inference of the treatment effect in the real-world population. Transportability methods re-weight individuallevel RCT data to balance baseline characteristics between RCT participants and a target population - in this case Veterans with T2D who meet RCT inclusion/exclusion criteria. Prior work from the investigator team has demonstrated the validity of transportability methods across a range of data settings and shown that these methods can accurately project treatment effects from one study population to a second. Transportability methods, therefore, provide a statistical tool to address the evidence gap between RCTs and real-world care. The proposal focuses on five recent RCTs in individuals with T2D: GRADE, CANVAS, EMPA-REG OUTCOME, LEADER, and SUSTAIN-6. GRADE compared four medications as second-line treatment for T2D in individuals with inadequate glucose control on metformin alone - a very common clinical scenario in the VA. CANVAS and EMPA-REG OUTCOME examined cardiovascular and renal outcomes associated with the SGL T2i canagliflozin and empagliflozin, respectively, the latter being the most commonly prescribed SGL T2i in the VA. LEADER and SUSTAIN-6 examined cardiovascular and renal outcomes associated with the GLP1 RA liraglutide and semaglutide, respectively - the two most frequently used GLP1 RA in the VA. Aim 1 will pr...