INTRODUCTION: Cardiovascular, renal, and metabolic diseases, collectively known as cardio-renal-metabolic (CRM) disease, interact and exacerbate each other, creating serious clinical and economic burdens. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are important therapeutic agents in managing CRM disease. Despite proven clinical benefits, the economic benefits of SGLT2i in the management of CRM diseases remain unclear. METHODS: We developed Markov models representing the natural progression of disease for two populations: a type 2 diabetes mellitus (T2DM) population and non-diabetic chronic kidney disease (non-DM CKD) population. These models incorporated key complications, including heart failure, myocardial infarction, stroke, CKD (for the T2DM population), and end-stage renal disease. A systematic literature search was conducted to determine input parameters. For each model, we estimated the 10-year medical costs, quality-adjusted life years (QALY), and incremental cost-effectiveness ratio (ICER) for SGLT2i treatment compared with conventional treatment. A probabilistic sensitivity analysis (PSA) and scenario analyses with conservative assumptions were performed. RESULTS: In the base-case analysis, SGLT2i treatment was estimated to increase QALY by 0.177 (7.090 vs 6.913 QALY
T2DM population) and 0.457 (6.980 vs 6.523 QALY
non-DM CKD population), and increase total medical costs by Japanese yen (JPY) 99,060 (JPY 762,524 vs 663,463
T2DM population) and JPY 229,810 (JPY 3,378,873 vs 3,149,063
non-DM CKD population), compared with conventional treatment. The ICER was JPY 559,175/QALY in the T2DM population and JPY 503,123/QALY in the non-DM CKD population. The PSA revealed that the probability of ICER being below the threshold value of JPY 5,000,000/QALY was 100% in the T2DM population and 98.7% in the non-DM CKD population, and the ICERs were below this threshold in all scenario analyses. CONCLUSION: SGLT2i treatment was demonstrated to be cost-effective in both the T2DM population and the non-DM CKD population, suggesting the potential of SGLT2i to offer significant clinical and economic benefits in the comprehensive management of CRM diseases.