ArticleScientific reports2026
Target trial emulation of sodium glucose cotransporter 2 inhibitors and clinical outcomes in diabetes and end stage kidney disease.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Patients with end-stage kidney disease (ESKD) have been largely excluded from randomized trials of sodium-glucose cotransporter-2 inhibitors (SGLT2is). Despite the lack of guideline recommendations, SGLT2i prescriptions occur in real-world clinical practice. We aimed to describe real-world associations between SGLT2i exposure and clinical outcomes among patients with type 2 diabetes mellitus (T2DM) coded with ESKD. We conducted a target trail emulation with retrospective, new-user, active-comparator cohort study using the TriNetX US Collaborative Network (2016-2023). Adults with T2DM and ESKD who initiated an SGLT2i or a dipeptidyl peptidase-4 inhibitor (DPP4i) were included. Propensity score matching (1:1) was used to balance baseline characteristics. The primary outcome was all-cause mortality; secondary outcomes included sepsis, pneumonia, major adverse cardiovascular events (MACE), all-cause hospitalization, and emergency department visits. Subgroup analyses were exploratory, and heterogeneity was assessed using Cochran's statistics. After matching, 5295 SGLT2i users were compared with 5295 DPP4i users. Over a follow-up of up to 4 years, SGLT2i exposure was associated with lower all-cause mortality (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.84-0.97), sepsis (HR 0.87, 95% CI 0.79-0.95), and all-cause hospitalization (HR 0.93, 95% CI 0.89-0.97). No significant associations were observed for MACE, pneumonia, or emergency department visits. Subgroup-specific estimates varied in magnitude, with no consistent evidence of heterogeneity. In this large real-world cohort of patients coded with ESKD, SGLT2i exposure was associated with favorable outcome patterns compared with DPP4i. Given the observational design, potential misclassification of kidney disease status, and off-label drug use, these findings should be interpreted as hypothesis-generating and do not establish causality.
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