Introduction
Drug | Target | Organ or tissue | Model | Effect |
---|---|---|---|---|
Empagliflozin | GLUT1 | Heart | Isolated failing human and murine cardiomyocytes | Improve glucose metabolism [1] |
Empagliflozin | HMGCS2 | Liver, kidney and jejunum | Normal and db/db mice | Increase serum ketone bodies [2] |
Empagliflozin | CPT1b | Heart | Otsuka long-evans tokushima fatty rats | Reduce fatty acid utilization [3] |
Empagliflozin | PPARγ/CD36 | Heart | Zucker diabetic fatty rats | Reduce the accumulation of fatty acids [4] |
Canagliflozin | PPAR-α | Adipose tissue | Obese mice due to a high-fat diet | Decrease plasma TG and TC [5] |
Dapagliflozin | Drp1 | Heart | High-fat diet-induced insulin-resistant obesity rats | Inhibit mitochondrial fission [6] |
Dapagliflozin, Empagliflozin | MFN1/MFN2 and OPA1 | Heart | Metabolic syndrome rats; high-fat diet/STZ-induced diabetic rats | |
Empagliflozin | PGC-1a, NRF-1 and mtTFA | Heart | High-fat diet/STZ-induced diabetic rats | Promote mitochondrial biogenesis [8] |
Empagliflozin, Dapagliflozin, Canagliflozin | ETC complex I and II | Human RPTEC/TERT1 cells | Normal | Improve the activity of ETC complex I and II (Canagliflozin reduce the activity of ETC complex I) [9] |
Dapagliflozin | O-GlcNAc transferase | Kidney | STZ-induced diabetic rats | May improve the activity of ETC complexes [10] |
Empagliflozin | Phenotype polarization of macrophages | The aorta | Mouse model of atherosclerosis with diabetes | |
Empagliflozin | AT1R and ACE | Coronary artery endothelium | High glucose-treated porcine coronary artery | Delay endothelial cell senescence [13] |
Luseogliflozin | GLUT9 isoform 2 | Xenopus laevis oocytes | Cells were injected with 0.1–25 ng of cRNA of GLUT9 isoform 2 | Reduce uric acid [14] |
Empagliflozin | COX-2 | The aorta | STZ-induced diabetes rats | Improve vascular dysfunction [15] |
Dapagliflozin | PKG/Kv channels | The rabbit aorta | Normal | Improve vascular dysfunction [16] |
Dapagliflozin; empagliflozin | TNF-α/ROS/NO | Human coronary arterial endothelial cells | TNF-α stimulation | Improve vascular dysfunction [17] |
empagliflozin | L-arginine/NO | Coronary arteries | ob/ob−/− mice | Improve vascular dysfunction [18] |
Empagliflozin; canagliflozin | NHE1 | Coronary arteries | Normal mice | Improve vascular dysfunction [19] |
Empagliflozin | AMP/ATP/AMPK/Drp1 | Heart | STZ-induced diabetic mice | Increase the number of CD31 + microvessels [20] |
Empagliflozin | AGEs/RAGE/PKC-ζ/MAPK | Kidney | STZ-induced diabetic rats | Inhibit fibrosis [21] |
Empagliflozin | TGF-β/SMAD | Heart | Genetic type 2 diabetes mouse model | Inhibit fibrosis [22] |
Dapagliflozin | STAT3 | Heart | Myocardial infarction in rats | Inhibit fibrosis [23] |
Empagliflozin | Heart | Human and murine HFpEF myocardium | Reduce cardiomyocyte stiffness [26] | |
Empagliflozin | Nrf2/ARE pathway | Heart | Genetic type 2 diabetes mouse model | Inhibit oxidative stress [22] |
Canagliflozin | AMPK/Akt/eNOS | Heart | ISO-induced oxidative stress in rats | Inhibit oxidative stress [27] |
Canagliflozin | iNOS, NOX4 | Heart | ISO-induced oxidative stress in rats | Inhibit oxidative stress [27] |
Empagliflozin | Liver and kidney | Otsuka long-evans tokushima fatty rats, rats with induced insulin resistance | ||
Dapagliflozin, Empagliflozin | ERK/Bax; STAT3/Bcl-2; AMPK/TNF-α; Caspase -3 | Heart | LPS-induced inflammation in mouse atrial myocytes; cardiorenal syndrome in rats; rats with cardiac I/R injury | |
Dapagliflozin | AMPK/NLRP3/ASC/caspase-1 pathway | Heart | BTBR ob/ob mice | Inhibit pyroptosis [34] |
Empagliflozin | CD36/AMPK/Ulk1/Beclin1 | Heart | ZDF rats | |
Empagliflozin | NHE1 and NHE1-related genes | Heart | db/db mice with myocardial infarction | Inhibit autophagy [36] |
Empagliflozin | Beclin1 | Heart | Myocardial infarction with acute hyperglycaemia in mice | Inhibit autophagy [37] |
Dapagliflozin | SIRT1/PERK/eIF2α/ATF4/CHOP | Heart | Heart pressure-overload in mice; myocardial I/R injury in mice | |
Dapagliflozin | Abundance of Akkermansia muciniphila | Gut | Diabetic mice homozygous for a point mutation in the leptin receptor gene | Improve glucose tolerance and atherosclerosis [40] |
Luseogliflozin, empagliflozin | The abundance of SCFA-producing bacteria | Gut | db/db mice |
SGLT2i and improved heart function
SGLT2i and the regulation of heart metabolism
SGLT2i and myocardial glucose utilization
SGLT2i and myocardial fat metabolism
SGLT2i and myocardial ketone body metabolism
SGLT2i and myocardial mitochondria
SGLT2i improve cardiovascular disease and microcirculation
SGLT2i attenuate vascular inflammation
SGLT2i regulates diastolic and systolic flow in blood vessels
SGLT2i increase microvessel density in the heart
SGLT2i improve ventricular compliance and myocardial fibrosis
SGLT2i inhibit oxidative stress
SGLT2i reduce the production of oxidative intermediates
SGLT2i increases antioxidant activity
In diabetes patients, SGLT2i rescue cardiomyocytes from programmed cell death
SGLT2i and myocardial apoptosis
SGLT2i and myocardial pyroptosis
SGLT2i and autophagy in the myocardium
SGLT2i reverse ER stress in diabetic cardiomyopathy
SGLT2i improve diabetic cardiomyopathy by regulating the intestinal microbiota
SGLT2i in clinical treatment
Drugs | Type | Object | Follow-up period | Effect of outcome |
---|---|---|---|---|
Multiple SGLT2i | Clinical trial | 77 first heart transplant recipients (37 patients with diabetes) | At least 6 months before surgery and 12 months after surgery | Reduce myocardial triglyceride accumulation [1] |
Empagliflozin | Randomized controlled trial | 97 participants with T2DM and coronary artery disease (CAD) | 6 months | Reduce LVM indexed to body surface area [2] |
Dapagliflozin | Randomized controlled trial | 66 patients with T2DM and LVH | 12 months | Reduce absolute LVM [3] |
Dapagliflozin | Randomized controlled trial | 97 patients with T2DM and atherosclerotic disease | 12 weeks | Increase FMD [4] |
Dapagliflozin | Randomized controlled trial | 16 patients with T2DM and stable coronary artery disease | 4 weeks | Increase MFR [5] |
Dapagliflozin | Clinical trial | 59 patients with T2DM | 6 weeks | Improve vascular remodelling [6] |
Multiple SGLT2i | Observational study | 583 diabetic AMI patients treated with percutaneous coronary intervention (PCI) | The use of SGLT2i started at least 3 months before hospitalization | Reduce infarct size after AMI [7] |
Empagliflozin | Clinical trial | 1549 patients with T2DM | 104 weeks | Reduce blood uric acid concentration [8] |
Dapagliflozin | Clinical trial | 3119 patients with heart failure | 12 months | Reduce blood uric acid concentration [9] |
Canagliflozin | Clinical trial | 2313 patients with T2DM | 26 weeks | Reduce blood uric acid concentration [10] |
Dapagliflozin | Randomized controlled trial | 44 patients with T2DM | 12 weeks | Did not change the composition of the gut flora [11] |
Multiple SGLT2i | Meta-analysis | 38,335 patients with type 2 diabetes | Median follow-up duration was 1.8 years | Reduce the risk of AF and AFL [12] |
Multiple SGLT2i | Meta-analysis | 1831 patients with acute heart failure with and without T2DM | Ranged from 60 days to 9 months | Reduce the risk of rehospitalization for heart failure and improve KCCQ score [13] |
Multiple SGLT2i | Meta-analysis | 10978 patients with T2DM with or without chronic heart failure | Ranged from 14 days to 1 year | Reduce NT-proBNP concentrations and improve cardiac diastolic function and LVEF [14] |