Beyond Diuresis and Glycemic Control: Comparative Analysis of Sodiumglucose Cotransporter-2 Inhibitors (SGLT2i) vs. Furosemide and Metformin in Heart Failure (HF) Patients with Type 2 Diabetes Mellitus (T2DM) Using the TriNetX Database

Introduction: Heart failure (HF) is prevalent and debilitating, particularly among individuals with type 2 diabetes mellitus (T2DM). This study compared outcomes associated with sodium–glucose cotransporter-2 inhibitors (SGLT2i) versus the combination of furosemide and metformin in patients with HF and T2DM. Methods: We used TriNetX, a global federated network of de-identified electronic health records from 98 healthcare organizations. Adults (≥18 years) with HF and T2DM were assigned to cohorts based on medication exposure. Propensity score matching (1:1) was performed to balance baseline characteristics. Outcomes were assessed using Cox models and Kaplan–Meier curves. Results: Among 208,761 eligible patients (SGLT2i = 4,847; furosemide and metformin = 203,914), 4,824 patients per group remained after matching. In the matched cohorts, SGLT2i use was associated with lower all-cause mortality (hazard ratio [HR] = 4.077 for furosemide and metformin vs. SGLT2i; p < 0.001) and reduced hospitalization risk (e.g., HR/RR estimates summarized in Tables 2 and 4; see figure caption for Cox HRs). At the end of the observed follow- up (median follow-up detailed in Table 3), Kaplan–Meier survival probability remained higher in the SGLT2i group (82.84%) compared with the furosemide and metformin group (21.33%). Given the magnitude of this absolute difference relative to randomized trials, residual confounding is likely despite matching. discussion: SGLT2 inhibitors demonstrated clear benefits over Furosemide + Metformin in reducing both mortality and hospitalization rates. The findings align with existing literature supporting SGLT2 inhibitors as a cornerstone therapy in patients with heart failure, especially in diabetic populations. The improved outcomes could be attributed to the pleiotropic effects of SGLT2 inhibitors, such as glucose regulation, diuresis, and cardiovascular protection. Conclusion: In this real-world analysis, SGLT2i use was associated with lower mortality and fewer hospitalizations compared with furosemide and metformin in patients with HF and T2DM. These findings should be interpreted as associations rather than causal effects due to the observational design and potential residual confounding. The results are hypothesis-generating and directionally consistent with prior randomized evidence.