What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Heart failure with ICD/CRT-D or device-based rhythm monitoring (n=861). Intervention: SGLT2 inhibitors vs. Placebo, standard therapy, or no SGLT2 inhibitor. Primary outcome: ICD therapy events (RR 0.53, 95% CI 0.38 to 0.74, p=0.0002).

What does this research mean for the field?

SGLT2 inhibitor therapy is associated with a significant reduction in ICD therapy events in heart failure patients with ICD or CRT-D devices, but shows no statistically significant reduction in overall arrhythmia events. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

September 25, 2026BMC Cardiovascular DisordersOpen Access

Effect of SGLT2 inhibitors on arrhythmic and device-therapy outcomes in heart failure patients with ICD/CRT-D: a systematic review and meta-analysis

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Key result

SGLT2 inhibitors reduce ICD therapy events by ~47% vs control in heart failure patients.

RR 0.53
95% CI 0.38 to 0.74
P=0.0002
n=861

Why the study?

Does SGLT2 inhibitor therapy reduce arrhythmic and device-therapy events in heart failure patients with ICD/CRT-D?

Key Points

To evaluate the association between sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapy and arrhythmic and device-therapy outcomes in heart failure patients with an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D).
Followed PRISMA 2020 guidance and searched PubMed, PubMed Central, Google Scholar, and ScienceDirect through 01 March 2026 (PROSPERO CRD420261299813).
Included 8 studies of adults with heart failure and an ICD/CRT-D or device-based rhythm monitoring receiving an SGLT2i versus placebo, standard therapy, or no SGLT2i.
Conducted random-effects meta-analyses using the DerSimonian-Laird estimator for any arrhythmia events and ICD therapy events, alongside leave-one-out and study-design-stratified sensitivity analyses.
For ICD therapy events (4 studies), SGLT2i therapy was associated with a significant reduction (RR 0.53, 95% CI 0.38 to 0.74, p = 0.0002; I2 = 0.0%), which remained consistent when restricted to randomized trials (RR 0.59, 95% CI 0.37 to 0.94) and after excluding the before-after study (RR 0.52, 95% CI 0.36 to 0.73).
For any arrhythmia events (5 studies), SGLT2i therapy was associated with a non-significant reduction (RR 0.82, 95% CI 0.53 to 1.25, p = 0.3485; I2 = 62.5%), with risk ratios ranging from 0.69 to 0.92 across sensitivity analyses.

Study Design

Type

Meta-Analysis (n=861)

Structured PICO

Does SGLT2 inhibitor therapy reduce arrhythmic and device-therapy events in heart failure patients with ICD/CRT-D?

Population

861 adults with heart failure and an ICD, CRT-D, or device-based rhythm monitoring included across 8 studies evaluating SGLT2 inhibitors.

Intervention

SGLT2 inhibitors as a class (including empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, or sotagliflozin) added to standard therapy or compared to a pre-treatment baseline period.

Comparator

Placebo, standard therapy without an SGLT2 inhibitor, or a within-study pre-treatment baseline period.

Outcome

Any arrhythmia events (broad composite of ventricular, supraventricular, and atrial rhythm endpoints) and ICD therapy events (device-delivered interventions including appropriate ATP, appropriate shock, or a composite of the two).composite

Main Result

Relative Risk: 0.53 (95% CI 0.38–0.74)

p-value: p=0.0002

SGLT2 inhibitors may significantly reduce appropriate ICD therapies in heart failure patients, though the evidence is currently limited by small study sizes and heterogeneous designs.

Limitations

Small number of contributing studies
Inclusion of a before-after study design with independent rather than paired groups
Inconsistent definitions of ICD therapy across studies
Serious risk of bias in the included non-randomized studies
Inclusion of a before-after design
Heterogeneous endpoints for the any arrhythmia events outcome

Implication

SGLT2i may reduce ICD therapies in device patients with HF; leaves open whether this extends to arrhythmia prevention or should change practice.

Abstract

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve heart failure outcomes, but their association with arrhythmic events and device-therapy endpoints in patients with implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) devices remains uncertain. Methods This systematic review and meta-analysis followed PRISMA 2020 guidance and was registered in PROSPERO (CRD420261299813). We searched PubMed, PubMed Central, Google Scholar, and ScienceDirect through 01 March 2026 for studies of adults with heart failure and an ICD/CRT-D, or device-based rhythm monitoring, who received an SGLT2 inhibitor versus placebo, standard therapy, or no SGLT2i. Random-effects meta-analysis (DerSimonian-Laird estimator, log risk-ratio scale) was performed for any arrhythmia events and ICD therapy events, with leave-one-out and study-design-stratified sensitivity analyses. Risk of bias was assessed with RoB 2 and ROBINS-I, and certainty of evidence with GRADE. Results We identified 169 records and included 8 studies in the review. Five studies contributed to the any arrhythmia events meta-analysis; SGLT2i therapy was associated with a non-significant reduction (RR 0.82, 95% CI 0.53 to 1.25, p = 0.3485; I2 = 62.5%), a result that stayed non-significant across leave-one-out and study-design-stratified analyses (RR range 0.69–0.92). Four studies contributed to ICD therapy events, where SGLT2i therapy was associated with a significant reduction (RR 0.53, 95% CI 0.38 to 0.74, p = 0.0002; I2 = 0.0%) that held when restricted to randomized trials (RR 0.59, 95% CI 0.37 to 0.94) and when the single before-after study was excluded (RR 0.52, 95% CI 0.36 to 0.73). Conclusion SGLT2i therapy was associated with a significant, design-consistent reduction in ICD therapy events, though this evidence remains low-certainty given the small number of contributing studies, the inclusion of a before-after design, and inconsistent definitions of ICD therapy across studies. The broader any arrhythmia outcome remained non-significant and uncertain. We interpret these findings as a hypothesis-generating signal of a possible reduction in device-treated arrhythmic events, not an established treatment effect, and larger, standardized, device-focused studies are still needed.

Discussion

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Cite This Study

Sohaib et al. (2026) conducted a meta-analysis in Heart failure with ICD/CRT-D or device-based rhythm monitoring (n=861). SGLT2 inhibitors vs. Placebo, standard therapy, or no SGLT2 inhibitor was evaluated on ICD therapy events (RR 0.53, 95% CI 0.38 to 0.74, p=0.0002). SGLT2 inhibitor therapy was associated with a significant 47% reduction in ICD therapy events (RR 0.53) compared to control in heart failure patients with ICD/CRT-D devices.

synapsesocial.com/papers/6ab60fbe406bf401c146895e https://doi.org/10.1186/s12872-026-06684-x