{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T19:52:54Z","timestamp":1781121174430,"version":"3.54.1"},"reference-count":87,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sodium-glucose co-transporter 2 (SGLT2) inhibitors facilitate urine glucose excretion by reducing glucose reabsorption, leading to ameliorate glycemic control. While the main characteristics of type 2 diabetes mellitus are insufficient insulin secretion and insulin resistance, SGLT2 inhibitors have some favorable effects on pancreatic \u03b2-cell function and insulin sensitivity. SGLT2 inhibitors ameliorate fatty liver and reduce visceral fat mass. Furthermore, it has been noted that SGLT2 inhibitors have cardio-protective and renal protective effects in addition to their glucose-lowering effect. In addition, several kinds of SGLT2 inhibitors are used in patients with type 1 diabetes mellitus as an adjuvant therapy to insulin. Taken together, SGLT2 inhibitors have amazing multifaceted effects that are far beyond prediction like some emerging magical medicine. Thereby, SGLT2 inhibitors are very promising as relatively new anti-diabetic drugs and are being paid attention in various aspects. It is noted, however, that SGLT2 inhibitors have several side effects such as urinary tract infection or genital infection. In addition, we should bear in mind the possibility of diabetic ketoacidosis, especially when we use SGLT2 inhibitors in patients with poor insulin secretory capacity.<\/jats:p>","DOI":"10.3390\/ijms22063062","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T11:48:22Z","timestamp":1615981702000},"page":"3062","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Unexpected Pleiotropic Effects of SGLT2 Inhibitors: Pearls and Pitfalls of This Novel Antidiabetic Class"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7898-1943","authenticated-orcid":false,"given":"Hideaki","family":"Kaneto","sequence":"first","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4984-4098","authenticated-orcid":false,"given":"Atsushi","family":"Obata","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Shimoda","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoe","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taka-aki","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"The First Department of Internal Medicine, Wakayama Medical University, Wakayama 641-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Kaku","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine 1, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1126\/science.1104345","article-title":"Type 2 diabetes-a matter of beta-cell life and death?","volume":"307","author":"Rhodes","year":"2005","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.2337\/dc14-0396","article-title":"\u03b2-Cell failure in type 2 diabetes: Postulated mechanisms and prospects for prevention and treatment","volume":"37","author":"Halban","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.jmb.2019.09.016","article-title":"Recent Insights Into Mechanisms of beta-Cell Lipo- and Glucolipotoxicity in Type 2 Diabetes","volume":"432","author":"Lytrivi","year":"2020","journal-title":"J. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/dom.13081","article-title":"Sodium-glucose cotransporter-2 inhibition improves incretin sensitivity of pan-creatic beta-cells in people with type 2 diabetes","volume":"20","author":"Ahn","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1055\/a-0591-9442","article-title":"Sequential Treatment Escalation with Dapagliflozin and Saxagliptin Improves Beta Cell Function in Type 2 Diabetic Patients on Previous Metformin Treatment: An Exploratory Mechanistic Study","volume":"50","author":"Forst","year":"2018","journal-title":"Horm. Metab. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.2337\/db17-1278","article-title":"Endogenous Glucose Production and Hormonal Changes in Response to Canagliflozin and Liraglutide Combination Therapy","volume":"67","author":"Martinez","year":"2018","journal-title":"Diabetes"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1111\/dom.13584","article-title":"Effect of canagliflozin treatment on hepatic triglyceride content and glucose metabolism in patients with type 2 diabetes","volume":"21","author":"Cusi","year":"2019","journal-title":"Diabetes Obes. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/s41574-020-0392-2","article-title":"Sodium\u2013glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus","volume":"16","author":"Scheen","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1210\/clinem\/dgaa494","article-title":"Improved Beta Cell Glucose Sensitivity Plays Predominant Role in the Decrease in HbA1c with Cana and Lira in T2DM","volume":"105","author":"Ali","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.2337\/dc18-2460","article-title":"Combination Therapy With Canagliflozin Plus Liraglutide Exerts Additive Effect on Weight Loss, but Not on HbA1c, in Patients With Type 2 Diabetes","volume":"43","author":"Ali","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/XCE.0000000000000209","article-title":"Sodium-glucose co-transporter 2 inhibitors and diabetic retinopathy: Insights into preservation of sight and looking beyond","volume":"10","author":"Lahoti","year":"2021","journal-title":"Cardiovasc. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6281","DOI":"10.3390\/ijms16036281","article-title":"Role of Pancreatic Transcription Factors in Maintenance of Mature \u03b2-Cell Function","volume":"16","author":"Kaneto","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kaneto, H., Obata, A., Kimura, T., Shimoda, M., Sanada, J., Fushimi, Y., Katakami, N., Matsuoka, T., and Kaku, K. (2020). Notable Underlying Mechanism for Pancreatic \u03b2-Cell Dysfunction and Atherosclerosis: Pleiotropic Roles of Incretin and Insulin Signaling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249444"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.2337\/db08-0693","article-title":"Regulation of MafA Expression in Pancreatic -Cells in db\/db Mice With Diabetes","volume":"59","author":"Matsuoka","year":"2010","journal-title":"Diabetes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7647","DOI":"10.1074\/jbc.M114.595579","article-title":"Preserving Mafa Expression in Diabetic Islet \u03b2-Cells Improves Glycemic Control in Vivo","volume":"290","author":"Matsuoka","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.bbrc.2016.12.128","article-title":"Recovered expression of Pdx1 improves \u03b2-cell failure in diabetic mice","volume":"483","author":"Yamamoto","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1007\/s00125-011-2069-9","article-title":"The human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes","volume":"54","author":"Shimoda","year":"2011","journal-title":"Diabetologia"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.mce.2014.11.018","article-title":"Protective effects of pioglitazone and\/or liraglutide on pancreatic \u03b2-cells in db\/db mice: Comparison of their effects between in an early and advanced stage of diabetes","volume":"400","author":"Kimura","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.mce.2015.06.010","article-title":"Combination of DPP-4 inhibitor and PPAR\u03b3 agonist exerts protective effects on pancreatic \u03b2-cells in diabetic db\/db mice through the augmentation of IRS-2 expression","volume":"413","author":"Hirukawa","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/dom.12005","article-title":"Vildagliptin preserves the mass and functionof pancreatic beta cells via the developmental regulation and suppression of oxidative stress and endoplasmic reticulum stress in a mouse model of diabetes","volume":"15","author":"Hamamoto","year":"2013","journal-title":"Diabetes Obes. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e001303","DOI":"10.1136\/bmjdrc-2020-001303","article-title":"Differential effects of sodium-glucose cotransporter 2 inhibitor and low-carbohydrate diet on body composition and metabolic profile in obese diabetic db\/db mice","volume":"8","author":"Kusakabe","year":"2020","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1530\/JOE-20-0354","article-title":"SGLT2-i improves markers of islet endothelial cell function in db\/db diabetic mice","volume":"248","author":"Hogan","year":"2021","journal-title":"J. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1172\/JCI26223","article-title":"Decreased vascular lesion formation in mice with inducible endothelial-specific expression of protein ki-nase Akt","volume":"116","author":"Mukai","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.cmet.2011.01.018","article-title":"Impaired Insulin Signaling in Endothelial Cells Reduces Insulin-Induced Glucose Uptake by Skeletal Muscle","volume":"13","author":"Kubota","year":"2011","journal-title":"Cell Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"876","DOI":"10.2337\/db14-0432","article-title":"Insu-lin receptor substrate-2 (Irs2) in endothelial cells plays a crucial role in insulin secretion","volume":"64","author":"Hashimoto","year":"2015","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1007\/s00125-019-4878-1","article-title":"Vascular endothelial PDK1 plays pivotal roles for maintenance of pancreatic beta-cell mass and function in adult male mice","volume":"62","author":"Obata","year":"2019","journal-title":"Diabetologia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1124\/jpet.112.191593","article-title":"Tofogliflozin, a potent and highly specific sodium\/glucose cotransporter 2 inhib-itor, improves glycemic control in diabetic rats and mice","volume":"341","author":"Suzuki","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1177\/1479164114563304","article-title":"Development of sotagliflozin, a dual sodium-dependent glucose trans-porter 1\/2 inhibitor","volume":"12","author":"Lapuerta","year":"2015","journal-title":"Diab. Vasc. Dis. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.2337\/db17-0055","article-title":"Inhibition of renal sodi-um-glucose cotransport with empagliflozin lowers fasting plasma glucose and improves beta-cell function in subjects with impaired fasting glucose","volume":"66","author":"Daniele","year":"2017","journal-title":"Diabetes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1210\/jc.2017-01838","article-title":"Empagli-flozin treatment is associated with improved beta-cell function in type 2 diabetes mellitus","volume":"103","author":"Daniele","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s00125-019-05071-w","article-title":"Luseogliflozin increases beta cell proliferation through humoral factors that activate an insulin receptor- and IGF-1 receptor-independent pathway","volume":"63","author":"Shirakawa","year":"2020","journal-title":"Diabetologia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"154324","DOI":"10.1016\/j.metabol.2020.154324","article-title":"Dapagliflozin promotes beta cell regeneration by inducing pancreatic endocrine cell phenotype conversion in type 2 diabetic mice","volume":"111","author":"Wei","year":"2020","journal-title":"Metabolism"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Saisho, Y. (2020). An emerging new concept for the management of type 2 diabetes with a paradigm shift from the glucose-centric to beta cell-centric concept of diabetes\u2014An Asian perspective. Expert Opin. Pharmacother., 1\u201313.","DOI":"10.1080\/14656566.2020.1776262"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.bbrc.2015.10.038","article-title":"Short-term selec-tive alleviation of glucotoxicity and lipotoxicity ameliorates the suppressed expression of key \u03b2-cell factors under diabetic conditions","volume":"467","author":"Shimo","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/j.bbrc.2015.10.109","article-title":"Protective ef-fects of SGLT2 inhibitor luseogliflozin on pancreatic \u03b2-cells in obese type 2 diabetic db\/db mice","volume":"470","author":"Okauchi","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1111\/dom.13400","article-title":"Protective effects of SGLT2 inhibitor luseogliflozin on pancreatic \u03b2-cells in obese diabetic db\/db mice: The earlier and longer, the better","volume":"20","author":"Kimura","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.beem.2015.10.002","article-title":"Evolving function and potential of pancreatic alpha cells","volume":"29","author":"Stanojevic","year":"2015","journal-title":"Best Pr. Res. Clin. Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/nm.3828","article-title":"Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion","volume":"21","author":"Bonner","year":"2015","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.diabet.2017.04.002","article-title":"Dapagliflozin modulates glucagon secretion in an SGLT2-independent manner in murine alpha cells","volume":"43","author":"Solini","year":"2017","journal-title":"Diabetes Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1007\/s00125-019-4849-6","article-title":"No direct effect of SGLT2 activity on glucagon secretion","volume":"62","author":"Kuhre","year":"2019","journal-title":"Diabetologia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ejphar.2014.01.040","article-title":"SGLT2 selective inhibitor ipragliflozin reduces body fat mass by increasing fatty acid oxidation in high-fat diet-induced obese rats","volume":"727","author":"Yokono","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e125","DOI":"10.1038\/nutd.2014.20","article-title":"Tofogliflozin, a sodium\/glucose cotransporter 2 inhibitor, attenuates body weight gain and fat accumulation in diabetic and obese animal models","volume":"4","author":"Suzuki","year":"2014","journal-title":"Nutr. Diabetes"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1172\/JCI74297","article-title":"Paradoxical insights into whole body metabolic adaptations following SGLT2 inhibition","volume":"124","author":"Cefalu","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1172\/JCI72227","article-title":"Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients","volume":"124","author":"Ferrannini","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1172\/JCI70704","article-title":"Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production","volume":"124","author":"Merovci","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1210\/en.2015-1588","article-title":"Tofogliflozin Improves Insulin Resistance in Skeletal Muscle and Accelerates Lipolysis in Adipose Tissue in Male Mice","volume":"157","author":"Obata","year":"2016","journal-title":"Endocrinology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/6470137","article-title":"Effect of Tofogliflozin on Body Composition and Glycemic Control in Japanese Subjects with Type 2 Diabetes Mellitus","volume":"2018","author":"Kamei","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1111\/jgh.13264","article-title":"Non-alcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syn-drome. Evidence from a systematic review and meta-analysis","volume":"31","author":"Ballestri","year":"2016","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Italian Association for the Study of the Liver (AISF) (2017). AISF position paper on nonalcoholic fatty liver disease (NAFLD): Up-dates and future directions. Dig Liver Dis., 49, 471\u2013483.","DOI":"10.1016\/j.dld.2017.01.147"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s12325-016-0306-9","article-title":"The Role of Nuclear Receptors in the Pathophysiology, Natural Course, and Drug Treatment of NAFLD in Humans","volume":"33","author":"Ballestri","year":"2016","journal-title":"Adv. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1001\/jama.2015.5370","article-title":"Nonalcoholic fatty liver disease: A systematic review","volume":"313","author":"Rinella","year":"2015","journal-title":"JAMA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2337\/dc16-1787","article-title":"Management of Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes: A Call to Action","volume":"40","author":"Bril","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1615\/CritRevOncog.2020035839","article-title":"Understanding the Alterations in Lipid Metabolism in NAFLD Progression: Current Trends and Future Directions","volume":"26","author":"Mungamuri","year":"2021","journal-title":"Crit. Rev. Oncog."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Han, M.A.T., Yu, Q., Tafesh, Z., and Pyrsopoulos, N. (2020). Diversity in NAFLD: A Review of Manifestations of Nonalcoholic Fatty Liver Disease in Different Ethnicities Globally. J. Clin. Transl. Hepatol., 1\u201310.","DOI":"10.14218\/JCTH.2020.00082"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1007\/s00125-016-3952-1","article-title":"Treatment of patients with type 2 diabetes and non-alcoholic fatty liver disease: Current approaches and future di-rections","volume":"59","author":"Cusi","year":"2016","journal-title":"Diabetologia"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40842-016-0027-7","article-title":"Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in patients with Type 2 Diabetes Mellitus","volume":"2","author":"Cusi","year":"2016","journal-title":"Clin. Diabetes Endocrinol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/hepr.12856","article-title":"Novel antidiabetic medications for non-alcoholic fatty liver disease with type 2 diabetes mellitus","volume":"47","author":"Sumida","year":"2017","journal-title":"Hepatol. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.2337\/dc17-0518","article-title":"Comparison of Ipragliflozin and Pioglitazone Effects on Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: A Randomized, 24-Week, Open-Label, Active-Controlled Trial","volume":"40","author":"Ito","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1007\/s13300-018-0447-8","article-title":"There is a close association between the re-covery of liver injury and glycemic control after SGLT2 inhibitor treatment in Japanese subjects with type 2 diabetes: A retro-spective clinical study","volume":"9","author":"Kinoshita","year":"2018","journal-title":"Diabetes Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1111\/jdi.13279","article-title":"Comparison of effects of three kinds of glucose-lowering drugs on nonalcoholic fatty liver disease in cases with type 2 diabetes: A ran-domized, open-label, 3-arm active-control study","volume":"11","author":"Kinoshita","year":"2020","journal-title":"J. Diabetes Investig."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"609135","DOI":"10.3389\/fendo.2020.609135","article-title":"Sodium-Glucose Co-Transporter 2 Inhibitors for Non-Alcoholic Fatty Liver Disease in Asian Patients With Type 2 Diabetes: A Meta-Analysis","volume":"11","author":"Wong","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, cardiovascular outcomes, and mor-tality in type 2 diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1161\/CIRCULATIONAHA.116.021887","article-title":"Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: Cardiovascular and kidney effects, potential mechanisms, and clinical applications","volume":"134","author":"Heerspink","year":"2016","journal-title":"Circulation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.2337\/dc16-0330","article-title":"CV Protection in the EMPA-REG OUTCOME Trial: A \u201cThrifty Substrate\u201d Hypothesis","volume":"39","author":"Ferrannini","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1056\/NEJMoa1611925","article-title":"Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes","volume":"377","author":"Neal","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1253\/circj.CJ-16-1148","article-title":"Empagliflozin and cardiovascular outcomes in Asian patients with type 2 diabetes and established cardiovascular disease\u2014Results from EM-PA-REG OUTCOME","volume":"81","author":"Kaku","year":"2017","journal-title":"Circ. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0140-6736(20)31824-9","article-title":"SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: A meta-analysis of the EMPER-OR-Reduced and DAPA-HF trials","volume":"396","author":"Zannad","year":"2020","journal-title":"Lancet"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/jdi.13329","article-title":"Sodium-glucose cotransporter 2 inhibitors represent a paradigm shift in the preven-tion of heart failure in type 2 diabetes patients","volume":"12","author":"Kashiwagi","year":"2021","journal-title":"J. Diabetes Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1056\/NEJMoa1811744","article-title":"Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy","volume":"380","author":"Perkovic","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.cmet.2019.04.011","article-title":"A Big Win for Diabetic Kidney Disease: CREDENCE","volume":"29","author":"Cherney","year":"2019","journal-title":"Cell Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/S2213-8587(19)30256-6","article-title":"SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: A systematic review and meta-analysis","volume":"7","author":"Neuen","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.kint.2019.04.004","article-title":"Light of dawn in Melbourne: SONAR and CREDENCE","volume":"96","author":"Nangaku","year":"2019","journal-title":"Kidney Int."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S2213-8587(20)30300-4","article-title":"Effects of canagliflozin on anaemia in patients with type 2 dia-betes and chronic kidney disease: A post-hoc analysis from the CREDENCE trial","volume":"8","author":"Oshima","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12933-020-01010-x","article-title":"Preventing major adverse cardiovascular events by SGLT-2 inhibition in patients with type 2 diabetes: The role of kidney","volume":"19","author":"Giugliano","year":"2020","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s13340-020-00444-8","article-title":"Significance of SGLT2 inhibitors: Lessons from renal clinical outcomes in patients with type 2 diabetes and basic researches","volume":"11","author":"Kitada","year":"2020","journal-title":"Diabetol. Int."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4861681","DOI":"10.1155\/2020\/4861681","article-title":"Effect of Combination Therapy of Canagliflozin Added to Teneligliptin Monotherapy in Japanese Subjects with Type 2 Diabetes Mellitus: A Retrospective Study","volume":"2020","author":"Fushimi","year":"2020","journal-title":"J. Diabetes Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1161\/CIRCULATIONAHA.118.037418","article-title":"Evaluation of glo-merular hemodynamic function by empagliflozin in diabetic mice using in vivo imaging","volume":"140","author":"Kidokoro","year":"2019","journal-title":"Circulation"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.cmet.2020.06.020","article-title":"SGLT2 Inhibition Mediates Protection from Diabetic Kidney Disease by Promoting Ketone Body-Induced mTORC1 Inhibition","volume":"32","author":"Tomita","year":"2020","journal-title":"Cell Metab."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-25054-y","article-title":"High Basolateral Glucose Increases Sodium-Glucose Cotransporter 2 and Reduces Sirtuin-1 in Renal Tubules through Glucose Transporter-2 Detection","volume":"8","author":"Umino","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1111\/dom.13961","article-title":"Interplay of adenosine monophosphate-activated protein kinase\/sirtuin-1 activation and sodium influx inhibition mediates the renal benefits of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes: A novel conceptual framework","volume":"22","author":"Parker","year":"2020","journal-title":"Diabetes Obes. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s40261-020-00949-9","article-title":"Sodium-Glucose Cotransporter Inhibitors for the Treatment of Type 1 Diabetes Mellitus","volume":"40","author":"Li","year":"2020","journal-title":"Clin. Drug Investig."},{"key":"ref_82","first-page":"325","article-title":"Short and Medium-Term Efficacy of Sodium Glucose Cotransporter-2 (SGLT-2) Inhibitors for the Treatment of Type 1 Diabetes: Systematic Review and Meta-Analysis","volume":"71","author":"Huang","year":"2020","journal-title":"Endokrynol. Polska"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/3971060","article-title":"Long-Term Effectiveness and Safety of SGLT-2 Inhibitors in an Italian Cohort of Patients with Type 2 Diabetes Mellitus","volume":"2019","author":"Mirabelli","year":"2019","journal-title":"J. Diabetes Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical Characteristics of Coronavirus Disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.dsx.2020.04.018","article-title":"Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia\u2014A systematic review, meta-analysis, and meta-regression","volume":"14","author":"Huang","year":"2020","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Mirabelli, M., Chiefari, E., Puccio, L., Foti, D.P., and Brunetti, A. (2020). Potential Benefits and Harms of Novel Antidiabetic Drugs During COVID-19 Crisis. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17103664"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/6\/3062\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:36:56Z","timestamp":1760161016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/6\/3062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,17]]},"references-count":87,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22063062"],"URL":"https:\/\/doi.org\/10.3390\/ijms22063062","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,17]]}}}