Sodium–glucose cotransporter-2 inhibitors as adjunctive therapy in left ventricular assist device recipients without diabetes: a real-world cohort study

Background Guideline-directed medical therapy (GDMT) after left ventricular assist device (LVAD) implantation improves outcomes; however, the role of sodium–glucose cotransporter-2 inhibitors (SGLT2i) in LVAD recipients without diabetes remains uncertain. Purpose To evaluate the association between SGLT2i use and clinical outcomes in non-diabetic LVAD recipients receiving contemporary GDMT. Methods We conducted a retrospective cohort study using the TriNetX federated electronic health record network of adult non-diabetic LVAD recipients implanted in the post–SGLT2i era, comparing SGLT2i-treated patients with propensity-matched GDMT-treated controls. Results After matching, 1,005 SGLT2i-treated patients were compared with 2,372 controls. SGLT2i use was associated with lower all-cause mortality at 6 months and 1 year (HR 0.44, 95% CI 0.35–0.57) and at 2 years (HR 0.51, 95% CI 0.42–0.63). AKI risk decreased over follow-up (HR 0.47–0.51). Sepsis rates were consistently lower. No differences were observed in device malfunction, and heart transplant rates were similar early on, but SGLT2i use favored heart transplantation at 2 years. Conclusions In LVAD recipients without diabetes receiving optimized GDMT, adjunctive SGLT2 inhibitor therapy was associated with significantly lower mortality, acute kidney injury, and sepsis across short- and intermediate-term follow-up, without excess device-related complications, and with a favorable signal for heart transplantation at 2 years. These findings are hypothesis-generating and support prospective evaluation of SGLT2i in contemporary LVAD care.