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Beyond Diuresis and Glycemic Control: Comparative Analysis of Sodiumglucose Cotransporter-2 Inhibitors (SGLT2i) vs.
Mohd Daise1, Qusai Alqudah1, Aseed Mestarihi1
1University of Central Florida College of Medicine, Graduate Medical Education/HCA Florida North Florida Hospital, Internal Medicine Residency Program, Gainesville, FL, USA.
Insights
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) use in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) was linked to reduced mortality and hospitalizations. This real-world study compared SGLT2i to furosemide and metformin.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Heart failure (HF) poses a significant burden, especially in patients with type 2 diabetes mellitus (T2DM).
- Comparing SGLT2 inhibitors (SGLT2i) with furosemide and metformin is crucial for managing co-existing HF and T2DM.
Purpose of the Study:
- To compare the real-world outcomes of SGLT2i versus furosemide and metformin in patients with HF and T2DM.
- To evaluate the association of SGLT2i with mortality and hospitalization rates in this specific patient population.
Main Methods:
- Utilized TriNetX, a federated network of de-identified electronic health records from 98 organizations.
- Conducted a 1:1 propensity score matching for adult patients (≥18 years) with HF and T2DM based on medication exposure.
- Assessed outcomes including all-cause mortality and hospitalization risk using Cox models and Kaplan-Meier curves.
Main Results:
- In matched cohorts (4,824 patients per group), SGLT2i use was associated with significantly lower all-cause mortality (HR < 0.001).
- SGLT2i demonstrated a reduced risk of hospitalization compared to furosemide and metformin.
- Kaplan-Meier survival probability was substantially higher in the SGLT2i group (82.84%) versus the furosemide and metformin group (21.33%).
Conclusions:
- Real-world analysis indicates SGLT2i use is associated with improved survival and fewer hospitalizations in T2DM patients with HF.
- Findings are hypothesis-generating and align with existing randomized trial data, though residual confounding is possible.
- SGLT2i represent a promising therapeutic option for managing patients with both heart failure and type 2 diabetes mellitus.
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.
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