Clinical and economic value of novel diabetes medications for prevention of cardiovascular disease in type 2 diabetes

PROJECT SUMMARY/ABSTRACT Individuals with type 2 diabetes (T2D) are at substantially increased risk for atherosclerotic cardiovascular disease (ASCVD) and heart failure, as well as other important outcomes such as end-stage renal disease (ESRD). Therefore, strategies to reduce these adverse health events in the T2D population are critically important. Cardiovascular safety concerns related to rosiglitazone led the Food and Drug Administration (FDA) to mandate cardiovascular outcome trials for new glucose lowering therapies. The cardiovascular outcome trials on two recently introduced glucose lowering classes of drugs, sodium glucose transporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists unexpectedly showed cardiovascular benefits with reduced rates of myocardial infarction, stroke, heart failure, and renal outcomes, particularly in those with established ASCVD. As a result, the FDA approved a new indication for three SGLT-2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) and three GLP-1 receptor agonists (liraglutide, dulaglutide and semaglutide) for reduction of cardiovascular events in those with T2D and established ASCVD. However, cardiovascular outcomes of these novel diabetes agents in T2D have only been evaluated in the context of very high ASCVD risk and as add-on treatment to standard T2D therapy. Wider use of these expensive novel medications by replacing cheaper standard drug regimens may yield uncertain effects on clinical outcomes and costs to the patient and the health system. We propose a decision-analytic approach to compare long-term clinical and economic outcomes of guideline-based and alternative treatment algorithms and identify optimal strategies for the use of SGLT2 inhibitors and GLP-1 receptor agonists. Insurance coverage and cost sharing can affect access and adherence to these agents and we will therefore additionally evaluate economic implications of their use from a patient perspective and address the potential disparities in utilization and cost-effectiveness across patients with T2D at different cardiovascular risk levels. Our specific aims are to assess differences in long-term clinical outcomes of strategies utilizing novel diabetes medications vs conventional care by combining meta- analysis of reconstructed trial survival data with prognostic and simulation modeling of epidemiologic data. First, we will compare guideline-based strategies of novel diabetes medication as second-line therapy vs alternative strategies including first-line usage and combination therapy across different target patient populations. Second, we will evaluate differences in lifetime quality-adjusted survival and costs of these various strategies utilizing novel diabetes medication with generally accepted societal benchmarks for cost-effective care as the criterion and address the impact of insurance coverage and cost sharing on treatment decisions. Thus, our research will rigorously evaluate clinical value and cost implications of novel pharmacologic approaches to prevention of ASCVD, heart failure and renal outcomes in patients with T2D. Identifying optimal prevention strategies that are economically sensible has the potential to improve public health in a cost-effective manner.