The changes of cardiac energy metabolism with sodium-glucose transporter 2 inhibitor therapy

Abstract

Background/aimsTo investigate the specific effects of s odium-glucose transporter 2 inhibitor (SGLT2i) on cardiac energy metabolism.MethodsA systematic literature search was conducted in eight databases. The retrieved studies were screened according to the inclusion and exclusion criteria, and relevant information was extracted according to the purpose of the study. Two researchers independently screened the studies, extracted information, and assessed article quality.ResultsThe results of the 34 included studies (including 10 clinical and 24 animal studies) showed that SGLT2i inhibited cardiac glucose uptake and glycolysis, but promoted fatty acid (FA) metabolism in most disease states. SGLT2i upregulated ketone metabolism, improved the structure and functions of myocardial mitochondria, alleviated oxidative stress of cardiomyocytes in all literatures. SGLT2i increased cardiac glucose oxidation in diabetes mellitus (DM) and cardiac FA metabolism in heart failure (HF). However, the regulatory effects of SGLT2i on cardiac FA metabolism in DM and cardiac glucose oxidation in HF varied with disease types, stages, and intervention duration of SGLT2i.ConclusionSGLT2i improved the efficiency of cardiac energy production by regulating FA, glucose and ketone metabolism, improving mitochondria structure and functions, and decreasing oxidative stress of cardiomyocytes under pathological conditions. Thus, SGLT2i is deemed to exert a benign regulatory effect on cardiac metabolic disorders in various diseases.Systematic review registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42023484295).

Ketone body levels and its associations with cardiac markers following an acute myocardial infarction: a post hoc analysis of the EMMY trial

“…Interestingly, a higher elevation in 3-βOHB was noted from baseline to 6 weeks, while its levels remained constant between 6 and 26 weeks. This trend in 3-βOHB over time is somewhat discrepant with previously reported preclinical data [ 28 ], which might be explained by different animal models, study populations, and follow-up time considered in these studies. Despite this, our finding supports the therapeutic potential of ketone bodies in post-MI patients and accentuates the need for further research in exploring the long-term impact of SGLT2i on ketone body metabolism and the mediation of beneficial cardiometabolic effects.…”

“…Although such evidence is scarce in post-AMI clinical settings, our findings are not surprising and agree with previous experimental and preclinical data, which showed a significant role of SGLT2 inhibition in promoting ketogenesis, ketonemia, and uptake and utilization of ketone bodies, especially 3-βOHB, in the myocardium [ 17 , 26 , 27 ]. A recent systematic review of clinical and animal studies also supported that SGLT2i treatment significantly upregulated ketone metabolism and increased its plasma levels [ 28 ]. Our study fills this research gap in the clinical scenario by showing that SGLT2i play a significant role in increasing or at least sustaining ketone body levels in patients with recent MI.…”