Effects of combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists on CRT response and clinical outcomes in in type 2 diabetes mellitus patients receiving chronic anti-diabetic medications: A multicenter observational study

Background: Type-2-diabetes-mellitus (T2DM) impairs outcomes in patients undergoing cardiac-resynchronization-therapy-with-defibrillator (CRTd). While both sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have cardiovascular benefits, their combination impact in CRTd-treated T2DM patients remains unclear. Methods: In this prospective multicenter observational study, 2,257 T2DM patients treated with CRTd were stratified into three groups: SGLT2i monotherapy (n 874), GLP-1RAs monotherapy (n 808), and combination therapy with GLP-1RAs/SGLT2i (n 575). Primary endpoints were CRT-response and heart failure (HF) hospitalizations at 1-year follow-up. Secondary endpoints included changes in glycemic control, renal function, inflammatory/oxidative markers, and cardiac deaths. Results: At 1 year, the combination therapy group had significantly higher CRT-response rate (66.3 %) compared to SGLT2i (59.6 %) and GLP-1RAs (59.2 %) groups (p = 0.014), and lower HF-hospitalization rates (15.7 % vs. 23.5 % and 24.4 %, respectively; p = 0.001). Multivariate Cox analysis confirmed combination therapy as an independent predictor of CRT response (HR 1.659, CI 95 % [1.320–2.085]; p 0.001) and reduced HF hospitalizations (0.822, CI 95 % [0.751–0.966]; p0.012) at 1 year of follow-up. Conclusions: In T2DM patients receiving CRTd, combination therapy with GLP-1RAs/SGLT2i was associated with improvements in cardiac function and clinical outcomes compared to monotherapy. GLP-1RAs/SGLT2i could optimize CRT responsiveness and reduce HF-hospitalizations in T2DM patients.