{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:53:10Z","timestamp":1792896790923,"version":"4.5.0"},"reference-count":89,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"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>Beyond their established hypoglycemic, cardioprotective, and nephroprotective properties, sodium\u2013glucose cotransporters 2 (SGLT2) inhibitors exert other pleiotropic actions on blood pressure levels, body weight, and lipid metabolism. Blood pressure (BP) reduction varies based on the background history, including an effect on systolic, diastolic BP, and 24 h BP measurements. The reduction in body weight between 1 and 2 kg for the first months is caused by a reduction in visceral and subcutaneous fat due to glycosuria and loss of calories. Regarding lipid metabolism, a reduction in triglycerides and an increase in total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) have been reported, although these alterations are small and could provide additional cardiovascular protection. Various pathophysiologic mechanisms have been proposed to explain the above-mentioned pleiotropic actions of SGLT2 inhibitors. Natriuresis, osmotic diuresis, body weight reduction, amelioration of endothelial dysfunction and arterial stiffness, sympathetic tone decrease, and uric acid reduction are among those that have been suggested for BP reduction. Apart from glycosuria and calorie loss, other mechanisms seem to contribute to body weight reduction, such as the beiging of white adipose tissue, while the mechanisms involved in lipid metabolism alterations have not been clearly determined.<\/jats:p>","DOI":"10.3390\/ijms252212384","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T13:03:14Z","timestamp":1731934994000},"page":"12384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Effects of SGLT2 Inhibitors on Blood Pressure and Other Cardiometabolic Risk Factors"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9180-6071","authenticated-orcid":false,"given":"Alexandra","family":"Katsimardou","sequence":"first","affiliation":[{"name":"2nd Department of Internal Medicine, 401 General Military Hospital of Athens, 11525 Athens, Greece"},{"name":"2nd Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, General Hospital \u201cHippokration\u201d, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9260-6306","authenticated-orcid":false,"given":"Panagiotis","family":"Theofilis","sequence":"additional","affiliation":[{"name":"Center for Nephrology \u201cG. Papadakis\u201d, General Hospital of Nikaia-Piraeus \u201cAg. Panteleimon\u201d, 18454 Nikaia, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Vordoni","sequence":"additional","affiliation":[{"name":"Center for Nephrology \u201cG. Papadakis\u201d, General Hospital of Nikaia-Piraeus \u201cAg. Panteleimon\u201d, 18454 Nikaia, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Doumas","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, 401 General Military Hospital of Athens, 11525 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7773-7575","authenticated-orcid":false,"given":"Rigas G.","family":"Kalaitzidis","sequence":"additional","affiliation":[{"name":"Center for Nephrology \u201cG. Papadakis\u201d, General Hospital of Nikaia-Piraeus \u201cAg. 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Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5335","DOI":"10.1074\/jbc.M117.779520","article-title":"SGLT2 Protein Expression Is Increased in Human Diabetic Nephropathy","volume":"292","author":"Wang","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41581-021-00393-8","article-title":"Pathophysiology of Diabetic Kidney Disease: Impact of SGLT2 Inhibitors","volume":"17","author":"DeFronzo","year":"2021","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/sj.ki.5002009","article-title":"Prevalence of Abnormal Serum Vitamin D, PTH, Calcium, and Phosphorus in Patients with Chronic Kidney Disease: Results of the Study to Evaluate Early Kidney Disease","volume":"71","author":"Levin","year":"2007","journal-title":"Kidney Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/ki.2009.87","article-title":"Renal Sodium\u2013Glucose Transport: Role in Diabetes Mellitus and Potential Clinical Implications","volume":"75","author":"Bakris","year":"2009","journal-title":"Kidney Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3427","DOI":"10.2337\/diabetes.54.12.3427","article-title":"Glucose Transporters in Human Renal Proximal Tubular Cells Isolated from the Urine of Patients With Non\u2013Insulin-Dependent Diabetes","volume":"54","author":"Rahmoune","year":"2005","journal-title":"Diabetes"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1681\/ASN.2017090958","article-title":"Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach","volume":"29","author":"Sethi","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/dom.13047","article-title":"Efficacy and Safety of Sodium-glucose Cotransporter-2 Inhibitors versus Dipeptidyl Peptidase-4 Inhibitors as Monotherapy or Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis","volume":"20","author":"Wang","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_11","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_12","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_13","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1056\/NEJMoa1911303","article-title":"Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction","volume":"381","author":"McMurray","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1056\/NEJMoa2022190","article-title":"Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure","volume":"383","author":"Packer","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJMoa2107038","article-title":"Empagliflozin in Heart Failure with a Preserved Ejection Fraction","volume":"385","author":"Anker","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1056\/NEJMoa2206286","article-title":"Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction","volume":"387","author":"Solomon","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1056\/NEJMoa2024816","article-title":"Dapagliflozin in Patients with Chronic Kidney Disease","volume":"383","author":"Heerspink","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"The EMPA-KIDNEY Collaborative Group, Herrington, W.G., Staplin, N., Wanner, C., Green, J.B., Hauske, S.J., Emberson, J.R., Preiss, D., Judge, P., and Mayne, K.J. (2023). Empagliflozin in Patients with Chronic Kidney Disease. N. Engl. J. Med., 388, 117\u2013127.","DOI":"10.1056\/NEJMoa2204233"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pescariu, S.A., Elagez, A., Nallapati, B., Bratosin, F., Bucur, A., Negru, A., Gaita, L., Citu, I.M., Popa, Z.L., and Barata, P.I. (2024). Examining the Impact of Ertugliflozin on Cardiovascular Outcomes in Patients with Diabetes and Metabolic Syndrome: A Systematic Review of Clinical Trials. Pharmaceuticals, 17.","DOI":"10.3390\/ph17070929"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1056\/NEJMoa2004967","article-title":"Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes","volume":"383","author":"Cannon","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"105","author":"Stevens","year":"2024","journal-title":"Kidney Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1097\/HJH.0000000000003480","article-title":"2023 ESH Guidelines for the Management of Arterial Hypertension the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension","volume":"41","author":"Mancia","year":"2023","journal-title":"J. Hypertens."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1001\/jama.2016.19043","article-title":"Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 Mm Hg, 1990\u20132015","volume":"317","author":"Forouzanfar","year":"2017","journal-title":"JAMA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/sj.jhh.1002001","article-title":"Statins: Another Class of Antihypertensive Agents?","volume":"20","author":"Milionis","year":"2006","journal-title":"J. Hum. Hypertens."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"420","DOI":"10.2337\/dc14-1096","article-title":"Empagliflozin Reduces Blood Pressure in Patients With Type 2 Diabetes and Hypertension","volume":"38","author":"Tikkanen","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S2213-8587(15)00417-9","article-title":"Blood Pressure and Glycaemic Effects of Dapagliflozin versus Placebo in Patients with Type 2 Diabetes on Combination Antihypertensive Therapy: A Randomised, Double-Blind, Placebo-Controlled, Phase 3 Study","volume":"4","author":"Weber","year":"2016","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.jash.2014.01.007","article-title":"Effects of Sodium-Glucose Co-Transporter 2 Inhibitors on Blood Pressure: A Systematic Review and Meta-Analysis","volume":"8","author":"Baker","year":"2014","journal-title":"J. Am. Soc. Hypertens."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1111\/dom.14451","article-title":"Comparative Efficacy of Glucose-lowering Medications on Body Weight and Blood Pressure in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-analysis","volume":"23","author":"Tsapas","year":"2021","journal-title":"Diabetes Obes. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"693","DOI":"10.2337\/dc18-2207","article-title":"Ambulatory Blood Pressure Reduction With SGLT-2 Inhibitors: Dose-Response Meta-Analysis and Comparative Evaluation with Low-Dose Hydrochlorothiazide","volume":"42","author":"Georgianos","year":"2019","journal-title":"Diabetes Care"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1080\/00325481.2023.2233492","article-title":"Novel Therapeutic Approaches in the Management of Chronic Kidney Disease: A Narrative Review","volume":"135","author":"Theofilis","year":"2023","journal-title":"Postgrad. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e019463","DOI":"10.1161\/JAHA.120.019463","article-title":"Effects of Sodium\/Glucose Cotransporter 2 (SGLT2) Inhibitors on Cardiovascular and Metabolic Outcomes in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials","volume":"10","author":"Teo","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s12933-022-01574-w","article-title":"Effect of Sodium-Glucose Cotransporter-2 Inhibitors on Blood Pressure in Patients with Heart Failure: A Systematic Review and Meta-Analysis","volume":"21","author":"Li","year":"2022","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.kint.2017.06.017","article-title":"Pooled Analysis of Phase III Trials Indicate Contrasting Influences of Renal Function on Blood Pressure, Body Weight, and HbA1c Reductions with Empagliflozin","volume":"93","author":"Cherney","year":"2018","journal-title":"Kidney Int."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Zanchi, A., Pruijm, M., Muller, M.-E., Ghajarzadeh-Wurzner, A., Maillard, M., Dufour, N., Bonny, O., Wuerzner, G., and Burnier, M. (2022). Twenty-Four Hour Blood Pressure Response to Empagliflozin and Its Determinants in Normotensive Non-Diabetic Subjects. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.854230"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1161\/CIRCULATIONAHA.118.037076","article-title":"Twenty-Four-Hour Blood Pressure\u2013Lowering Effect of a Sodium-Glucose Cotransporter 2 Inhibitor in Patients with Diabetes and Uncontrolled Nocturnal Hypertension","volume":"139","author":"Kario","year":"2019","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1111\/jch.13367","article-title":"Effect of Canagliflozin on Nocturnal Home Blood Pressure in Japanese Patients with Type 2 Diabetes Mellitus: The SHIFT-J Study","volume":"20","author":"Kario","year":"2018","journal-title":"J. Clin. Hypertens."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1161\/CIRCULATIONAHA.118.036568","article-title":"Antihyperglycemic and Blood Pressure Effects of Empagliflozin in Black Patients with Type 2 Diabetes Mellitus and Hypertension","volume":"139","author":"Ferdinand","year":"2019","journal-title":"Circulation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1097\/HJH.0000000000002690","article-title":"Dapagliflozin Decreases Ambulatory Central Blood Pressure and Pulse Wave Velocity in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial","volume":"39","author":"Papadopoulou","year":"2021","journal-title":"J. Hypertens."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1111\/jch.13988","article-title":"Effects of Luseogliflozin on Arterial Properties in Patients with Type 2 Diabetes Mellitus: The Multicenter, Exploratory LUSCAR Study","volume":"22","author":"Kario","year":"2020","journal-title":"J. Clin. Hypertens."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41440-023-01494-6","article-title":"Long-Term Effects of Ipragliflozin on Blood Pressure in Patients with Type 2 Diabetes: Insights from the Randomized PROTECT Trial","volume":"47","author":"Saito","year":"2024","journal-title":"Hypertens. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1161\/CIRCULATIONAHA.120.048740","article-title":"Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease","volume":"143","author":"Ye","year":"2021","journal-title":"Circulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S112","DOI":"10.1016\/j.ekir.2022.01.274","article-title":"POS-255 Effect of Dapagliflozin on Blood Pressure in Patients with CKD: A Pre-Specified Analysis from DAPA-CKD","volume":"7","author":"Provenzano","year":"2022","journal-title":"Kidney Int. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1681\/ASN.0000000000000271","article-title":"Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD","volume":"35","author":"Mayne","year":"2024","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S2213-8587(13)70208-0","article-title":"Efficacy and Safety of Empagliflozin Added to Existing Antidiabetes Treatment in Patients with Type 2 Diabetes and Chronic Kidney Disease: A Randomised, Double-Blind, Placebo-Controlled Trial","volume":"2","author":"Barnett","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12933-019-0912-3","article-title":"Improved Home BP Profile with Dapagliflozin Is Associated with Amelioration of Albuminuria in Japanese Patients with Diabetic Nephropathy: The Yokohama Add-on Inhibitory Efficacy of Dapagliflozin on Albuminuria in Japanese Patients with Type 2 Diabetes Study (Y-AIDA Study)","volume":"18","author":"Kinguchi","year":"2019","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/ejhf.2915","article-title":"Renal and Blood Pressure Effects of Dapagliflozin in Recently Hospitalized Patients with Heart Failure with Mildly Reduced or Preserved Ejection Fraction: Insights from the DELIVER Trial","volume":"25","author":"Chatur","year":"2023","journal-title":"Eur. J. Heart Fail."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1056\/NEJMra2115011","article-title":"Gliflozins in the Management of Cardiovascular Disease","volume":"386","author":"Braunwald","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.34067\/KID.0001172021","article-title":"EGFR Decline after SGLT2 Inhibitor Initiation: The Tortoise and the Hare Reimagined","volume":"2","author":"Weinstein","year":"2021","journal-title":"Kidney360"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"F712","DOI":"10.1152\/ajprenal.00264.2020","article-title":"A Role for Tubular Na+\/H+ Exchanger NHE3 in the Natriuretic Effect of the SGLT2 Inhibitor Empagliflozin","volume":"319","author":"Onishi","year":"2020","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1177\/1358863X221101653","article-title":"Effect of Sodium-Glucose Co-Transporter-2 Inhibitors on Arterial Stiffness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"27","author":"Patoulias","year":"2022","journal-title":"Vasc. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e016173","DOI":"10.1161\/JAHA.119.016173","article-title":"Acute and Chronic Effects of SGLT2 Inhibitor Empagliflozin on Renal Oxygenation and Blood Pressure Control in Nondiabetic Normotensive Subjects: A Randomized, Placebo-Controlled Trial","volume":"9","author":"Zanchi","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.amjcard.2021.11.003","article-title":"Meta-Analysis Addressing the Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Flow-Mediated Dilation in Patients with Type 2 Diabetes Mellitus","volume":"165","author":"Patoulias","year":"2022","journal-title":"Am. J. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"109927","DOI":"10.1016\/j.diabres.2022.109927","article-title":"Pleiotropic effects of SGLT2 inhibitors and heart failure outcomes","volume":"188","author":"Theofilis","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Theofilis, P., Sagris, M., Oikonomou, E., Antonopoulos, A.S., Siasos, G., Tsioufis, C., and Tousoulis, D. (2021). Inflammatory Mechanisms Contributing to Endothelial Dysfunction. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070781"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Nakao, M., Shimizu, I., Katsuumi, G., Yoshida, Y., Suda, M., Hayashi, Y., Ikegami, R., Hsiao, Y.T., Okuda, S., and Soga, T. (2021). Empagliflozin Maintains Capillarization and Improves Cardiac Function in a Murine Model of Left Ventricular Pressure Overload. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-97787-2"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.pharep.2019.06.004","article-title":"Effects of Ticagrelor, Empagliflozin and Tamoxifen against Experimentally-Induced Vascular Reactivity Defects in Rats in Vivo and in Vitro","volume":"71","year":"2019","journal-title":"Pharmacol. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.lfs.2018.01.032","article-title":"The Anti-Diabetic Drug Dapagliflozin Induces Vasodilation via Activation of PKG and Kv Channels","volume":"197","author":"Li","year":"2018","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1161\/CIRCULATIONAHA.118.038881","article-title":"Possible Mechanism of Hematocrit Elevation by Sodium Glucose Cotransporter 2 Inhibitors and Associated Beneficial Renal and Cardiovascular Effects","volume":"139","author":"Sano","year":"2019","journal-title":"Circulation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"119018","DOI":"10.1016\/j.lfs.2021.119018","article-title":"Role of Sodium Glucose Cotransporter Type 2 Inhibitors Dapagliflozin on Diabetic Nephropathy in Rats; Inflammation, Angiogenesis and Apoptosis","volume":"280","author":"Elkazzaz","year":"2021","journal-title":"Life Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1007\/s00592-021-01681-2","article-title":"Sodium-Glucose Cotransporter 2 Inhibition Prevents Renal Fibrosis in Cyclosporine Nephropathy","volume":"58","author":"Castoldi","year":"2021","journal-title":"Acta Diabetol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"27","DOI":"10.33594\/000000003","article-title":"Effects of the SGLT-2 Inhibitor Canagliflozin on Adenine-Induced Chronic Kidney Disease in Rats","volume":"52","author":"Ali","year":"2019","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Yang, W., Li, X., He, L., Zhu, S., Lai, S., Zhang, X., Huang, Z., Yu, B., Cui, C., and Wang, Q. (2023). Empagliflozin Improves Renal Ischemia\u2013Reperfusion Injury by Reducing Inflammation and Enhancing Mitochondrial Fusion through AMPK\u2013OPA1 Pathway Promotion. Cell Mol. Biol. Lett., 28.","DOI":"10.1186\/s11658-023-00457-6"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Xu, J., Kitada, M., Ogura, Y., Liu, H., and Koya, D. (2021). Dapagliflozin Restores Impaired Autophagy and Suppresses Inflammation in High Glucose-Treated HK-2 Cells. Cells, 10.","DOI":"10.3390\/cells10061457"},{"key":"ref_65","first-page":"2082145","article-title":"The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment with Pro- and Antioxidant Properties in Chronic Diseases","volume":"2020","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Behnammanesh, G., Durante, G.L., Khanna, Y.P., Peyton, K.J., and Durante, W. (2020). Canagliflozin Inhibits Vascular Smooth Muscle Cell Proliferation and Migration: Role of Heme Oxygenase-1. Redox Biol., 32.","DOI":"10.1016\/j.redox.2020.101527"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Takahashi, H., Nomiyama, T., Terawaki, Y., Horikawa, T., Kawanami, T., Hamaguchi, Y., Tanaka, T., Motonaga, R., Fukuda, T., and Tanabe, M. (2019). Combined Treatment with DPP-4 Inhibitor Linagliptin and SGLT2 Inhibitor Empagliflozin Attenuates Neointima Formation after Vascular Injury in Diabetic Mice. Biochem. Biophys. Rep., 18.","DOI":"10.1016\/j.bbrep.2019.100640"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jacbts.2019.11.007","article-title":"SGLT2 Inhibitor\u2013Induced Sympathoinhibition","volume":"5","author":"Herat","year":"2020","journal-title":"JACC Basic. Transl. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Zhang, L., Li, J., Zhang, L., Guo, L., Li, H., and Li, D. (2018). Association and Interaction Analysis of Body Mass Index and Triglycerides Level with Blood Pressure in Elderly Individuals in China. Biomed. Res. Int., 2018.","DOI":"10.1155\/2018\/8934534"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e533","DOI":"10.52225\/narra.v4i1.533","article-title":"Positive Correlation between Body Weight and Body Mass Index with Blood Pressure in Young Adults","volume":"4","author":"Yusni","year":"2024","journal-title":"Narra J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.diabres.2017.11.016","article-title":"Increased Sugar Intake as a Form of Compensatory Hyperphagia in Patients with Type 2 Diabetes under Dapagliflozin Treatment","volume":"135","author":"Horie","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1016\/S0140-6736(13)60683-2","article-title":"Efficacy and Safety of Canagliflozin versus Glimepiride in Patients with Type 2 Diabetes Inadequately Controlled with Metformin (CANTATA-SU): 52 Week Results from a Randomised, Double-Blind, Phase 3 Non-Inferiority Trial","volume":"382","author":"Cefalu","year":"2013","journal-title":"Lancet"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Matthews, J.R., Herat, L.Y., Magno, A.L., Gorman, S., Schlaich, M.P., and Matthews, V.B. (2020). SGLT2 Inhibitor-Induced Sympathoexcitation in White Adipose Tissue: A Novel Mechanism for Beiging. Biomedicines, 8.","DOI":"10.3390\/biomedicines8110514"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ebiom.2017.05.028","article-title":"SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-Induced Obese Mice","volume":"20","author":"Xu","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1111\/bph.15381","article-title":"Inhibition of the Sodium-Glucose Co-Transporter SGLT2 by Canagliflozin Ameliorates Diet-Induced Obesity by Increasing Intra-Adipose Sympathetic Innervation","volume":"178","author":"Yang","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Lv, Y., Zhao, C., Jiang, Q., Rong, Y., Ma, M., Liang, L., Li, W., Zhang, J., Xu, N., and Wu, H. (2024). Dapagliflozin Promotes Browning of White Adipose Tissue through the FGFR1-LKB1-AMPK Signaling Pathway. Mol. Biol. Rep., 51.","DOI":"10.1007\/s11033-024-09540-3"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Xiang, L., Liu, M., Xiang, G., Yue, L., Zhang, J., Xu, X., and Dong, J. (2024). Dapagliflozin Promotes White Adipose Tissue Browning Though Regulating Angiogenesis in High Fat Induced Obese Mice. BMC Pharmacol. Toxicol., 25.","DOI":"10.1186\/s40360-024-00747-5"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e000783","DOI":"10.1136\/bmjdrc-2019-000783","article-title":"Empagliflozin Reverses Obesity and Insulin Resistance through Fat Browning and Alternative Macrophage Activation in Mice Fed a High-Fat Diet","volume":"7","author":"Xu","year":"2019","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7505","DOI":"10.3390\/cimb46070445","article-title":"Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Transcription Regulation of AgRP and POMC Genes","volume":"46","author":"Kim","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_80","first-page":"1113","article-title":"SGLT-2 Inhibitors: Pharmacokinetics Characteristics and Effects on Lipids","volume":"14","author":"Tsimihodimos","year":"2018","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"105068","DOI":"10.1016\/j.phrs.2020.105068","article-title":"Effect of Sodium-Glucose Co-Transporter 2 Inhibitors on Lipid Profile: A Systematic Review and Meta-Analysis of 48 Randomized Controlled Trials","volume":"160","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"117236","DOI":"10.1016\/j.atherosclerosis.2023.117236","article-title":"SGLT2-Inhibition Increases Total, LDL, and HDL Cholesterol and Lowers Triglycerides: Meta-Analyses of 60 Randomized Trials, Overall and by Dose, Ethnicity, and Drug Type","volume":"394","author":"Bechmann","year":"2024","journal-title":"Atherosclerosis"},{"key":"ref_83","first-page":"e66145","article-title":"Safety and Efficacy of Remogliflozin in People with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis","volume":"16","author":"Tewari","year":"2024","journal-title":"Cureus"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"120543","DOI":"10.1016\/j.lfs.2022.120543","article-title":"Characteristics and Molecular Mechanisms through Which SGLT2 Inhibitors Improve Metabolic Diseases: A Mechanism Review","volume":"300","author":"Lingli","year":"2022","journal-title":"Life Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12933-016-0491-5","article-title":"Dapagliflozin Decreases Small Dense Low-Density Lipoprotein-Cholesterol and Increases High-Density Lipoprotein 2-Cholesterol in Patients with Type 2 Diabetes: Comparison with Sitagliptin","volume":"16","author":"Hayashi","year":"2017","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Katsuyama, H., Horinaka, S., Hakoshima, M., Adachi, H., and Yanai, H. (2024). Retrospective Longitudinal Observational Study on the Long-Term Effects of Sodium-Glucose Cotransporter-2 Inhibitors on the Development of Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetic Japanese Patients. J. Clin. Med., 13.","DOI":"10.20944\/preprints202407.1916.v1"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Bessho, R., Takiyama, Y., Takiyama, T., Kitsunai, H., Takeda, Y., Sakagami, H., and Ota, T. (2019). Hypoxia-Inducible Factor-1\u03b1 Is the Therapeutic Target of the SGLT2 Inhibitor for Diabetic Nephropathy. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-51343-1"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e22410","DOI":"10.1096\/fj.202200243R","article-title":"SGLT2 Inhibitor Dapagliflozin Attenuates Cardiac Fibrosis and Inflammation by Reverting the HIF-2\u03b1 Signaling Pathway in Arrhythmogenic Cardiomyopathy","volume":"36","author":"Yang","year":"2022","journal-title":"FASEB J."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"531","DOI":"10.2215\/CJN.0000000000000362","article-title":"Alleviation of Anemia by SGLT2 Inhibitors in Patients with CKD: Mechanisms and Results of Long-Term Placebo-Controlled Trials","volume":"19","author":"Packer","year":"2023","journal-title":"Clin. J. Am. Soc. Nephrol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/22\/12384\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:34:46Z","timestamp":1760114086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/22\/12384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,18]]},"references-count":89,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252212384"],"URL":"https:\/\/doi.org\/10.3390\/ijms252212384","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,18]]}}}