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

Division

North Florida

Hospital

North Florida Regional Medical Center

Document Type

Manuscript

Publication Date

1-20-2026

Keywords

Heart failure, SGLT2 inhibitors, comparative effectiveness, diabetes, furosemide, metformin

Disciplines

Endocrine System Diseases | Internal Medicine | Medicine and Health Sciences

Abstract

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.

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.

Publisher or Conference

Cardiovascular & Hematological Agents in Medicinal Chemistry

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