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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

Abstract

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.

Autori

Celestino Sardu a b c d , Ludovica Vittoria Marfella a , Luca Rinaldi a , Ferdinando Carlo Sasso a b , Domenico Cozzolino a , Francesco Nappo a , Ausilia Sellitto a , Ciro Romano a , Caterina Carusone a , Nunzia D’Onofrio e , Maria Consiglia Trotta e , Joshua Riccio a , Domenico Cioffi a , Mario Volpicelli f , Carmine La Marca f , Natale Marrazzo c , Valerio Giordano g , Carlo Fumagalli a d , Alessandro Landolfi d , Marianna Abitabile a … Raffaele Marfella a b

Articolo Completo

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Celestino sardu medico cardiologo
Prof. Dott. Celestino Sardu

Cardiologo

Il Prof. Dottor Celestino Sardu Cardiologo, dal momento della sua presa in servizio, ha svolto attività di ricerca presso cattedra di Medicina Interna dell’Università della Campania “Luigi Vanvitelli” e in collaborazione con Centri esteri degli Stati Uniti d’ America (Tample University, Philadelphia; A. Einstein College of Medicine, NYC; Stanford University, Paolo Alto; USA)

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