Sirtuins and regulatory microRNAs (miRNAs) as epigenetic determinants of empagliflozin-mediated recovery after acute myocardial infarction
An erratum to this article was published (Cardiovasc Diabetol, 3 May 2026 ↗)
Authors' conclusion
Baseline levels of SIRT2, SIRT4, miR-182-5p, and miR-302a-3p were identified as predictors of ΔLVEF < 11% changes after 26-weeks of treatment, which suggests their potential for stratifying responders and non-responders to empagliflozin. The combined panel of these markers demonstrated the highest predictive accuracy, suggesting the epigenetic influence of SGLT2 inhibitors and the potential for genomic characterization in personalized treatment approaches.
Study context
- Population
- Patients after acute myocardial infarction with samples at baseline and after 26 weeks
- Participants
- 227 patients
- Comparison
- Empagliflozin vs placebo for 26 weeks after acute myocardial infarction (AMI)
- Outcome
- Sirtuin expression
- Follow-up
- 26 weeks
Methodological detailsplacebo-controlled, SHAP analysis, miRNA target prediction and enrichment analyses
- Placebo-controlled
- SHAP analysis
- miRNA target prediction and enrichment analyses
Main finding
As reported in the abstract
- Reduction in SIRT6 expression in placebo
- p = 0.006
Further findings
Baseline predictors of ΔLVEF < 11% improvement with empagliflozin · 26 weeks
- SIRT2 AUC
- 0.806
- SIRT4 AUC
- 0.765
- miR-182-5p AUC
- 0.716
- miR-302a-3p AUC
- 0.757
- Combined panel cross-validated AUC
- 0.890
- Combined panel sensitivity
- 81%
- Combined panel specificity
- 90%
- Combined panel OR, adjusted for age, sex, hypertension, BMI, ezetimibe
- 18.70 (95% CI 5.78-60.49)
- Baseline NT-proBNP did not significantly predict an unfavorable outcome
- ΔLVEF cut-off 11% from third quartile in empagliflozin group
- Individual markers: both p < 0.01
Original publication
Sirtuins and regulatory miRNAs as epigenetic determinants of empagliflozin-mediated recovery after acute myocardial infarction. Cardiovasc Diabetol. Published 29 December 2025. doi:10.
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