SGLT receptors and myocardial ischaemia-reperfusion injury: inhibition of SGLT-1, SGLT-2, or both?
Abstract
This editorial refers to ‘Cardiac sodium-dependent glucose cotransporter 1 is a novel mediator of ischaemia/reperfusion injury’, by Z. Li et al., pp. 1646–1658. The publication of three randomized controlled trials of SGLT2 inhibitors demonstrating significant improvement in cardiovascular death among Type 2 Diabetes Mellitus patients receptors1–3 sparkled interest in the SGLT receptors.4 These cardiac benefits were mostly achieved by a significant reduction in heart failure re-hospitalizations without impact on ischaemic events (myocardial infarction or stroke). The fast separation of the event curves in these trials (within the first 2–3 months) supports the existence of a mechanism unrelated to their glucose-lowering effect5,6; in fact, we have demonstrated that the SGLT2 inhibitor empagliflozin ameliorates heart failure and enhances myocardial energetic status via a shift in the myocardial sources of metabolism from glucose towards fatty acids, ketone bodies, and branched-chain aminoacids.7 However, most of the research is focused on SGLT receptors and heart failure, while ischaemia-reperfusion (I/R) injury has not received attention. Li et al.8 aim is to focus on this unexplored topic of the effect of SGLT receptors and myocardial I/R. SGLT receptors are simporters of glucose and sodium (moving both molecules in the same direction); they obtain energy to transport glucose against a concentration gradient by coupling it to the downhill Na+ electromechanical gradient.4,5…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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