Sodium-glucose cotransporter-2 inhibitors in individuals with ischemia reperfusion injury: A systematic review

Background: The effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on ischemia reperfusion injury (IRI) is a novel concept and only limited number of animals studies have yet been investigated. We aimed to perform a systematic review of literature to explore the clinical studies which investigated the effects of SGLT-2 inhibitors on myocardial IRI setting.Methods: We searched MEDLINE, Embase, and Cochrane Library from inception until December 7th, 2023. ClinicalTrials.gov was also explored for ongoing studies. Two authors independently conducted the literature search, examined the studies, and evaluated the eligibility criteria. Any disagreements or uncertainties were resolved by the corresponding author. The search strategy followed the PICO process (Population, Intervention, Comparison, and Outcome) and Emtree was used to select relevant keywords.Results: Of 220 articles identified from the literature research, five articles were included in the study, of which three studies lately were retracted. The remaining studies included 1229 participants, with 209 receiving SGLT-2 inhibitors and 1090 not receiving them. All of the participants were diabetic patients admitted with acute myocardial infarction (AMI), undergoing percutaneous coronary intervention (PCI). The results demonstrated that the use of SGLT-2 inhibitors is associated with lower troponin levels, and higher rates of ST resolution. The results of the studies also showed smaller infarct sizes, lower inflammatory biomarkers and improved left ventricular function at discharge among SGLT-2 inhibitor users.Conclusion: In line with in vivo and ex vivo findings, the results of this systematic review supported benefits of SGLT-2 inhibitors in IRI through reducing infarct size and inflammatory biomarkers. However, further clinical trials are warranted to provide robust evidence.