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

🎖️ Top 10% JournalSep 5, 2025Diabetes research and clinical practice

Effects of combining two diabetes drugs on heart function and health outcomes in type 2 diabetes patients already on long-term treatment

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Abstract

At 1 year, the combination therapy group had a 66.3% CRT-response rate, significantly higher than the SGLT2i (59.6%) and GLP-1RAs (59.2%) groups.

Combination therapy with GLP-1RAs and SGLT2i was associated with lower heart failure hospitalization rates (15.7%) compared to SGLT2i (23.5%) and GLP-1RAs (24.4%).
Multivariate analysis indicated that combination therapy is an independent predictor of CRT response and reduced heart failure hospitalizations.
Improvements in cardiac function and clinical outcomes were observed in T2DM patients receiving combination therapy compared to those on monotherapy.

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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.

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