{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:55:26Z","timestamp":1790654126177,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Sodium\u2010glucose cotransporter\u20102 inhibitors (SGLT2is) improve cardiovascular and kidney outcomes, but their effects on circulating inflammatory biomarkers remain uncertain. We systematically reviewed randomized evidence on the effects of SGLT2is on peripheral\u2010blood inflammatory biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Ovid MEDLINE, Scopus, Web of Science, and the Cochrane Library were searched from database inception to January 15, 2026. Randomized controlled trials enrolling adults and reporting at least one prespecified circulating inflammatory biomarker were included. Random\u2010effects meta\u2010analyses used restricted maximum likelihood estimation with Hartung\u2013Knapp\u2010adjusted inference. Eligible studies without effect estimates and variance data compatible with quantitative pooling were synthesized narratively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forty\u2010seven randomized trials reported across 48 publications met the eligibility criteria; 38 trials contributed to at least one quantitative synthesis and 9 were synthesized narratively only. SGLT2i therapy did not significantly reduce CRP\/hsCRP (MD \u22121.13\u2009mg\/L; 95% CI \u22122.31 to 0.05;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200992.6%) or IL\u20106 (MD \u22121.53\u2009pg\/mL; 95% CI \u22123.69 to 0.64;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200989.8%). TNF\u2010\u03b1 showed a small reduction in the primary analysis (SMD \u22120.39; 95% CI \u22120.71 to \u22120.07;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200973.7%), although its prediction interval crossed the null. Narrative findings were mixed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SGLT2i therapy did not show statistically significant reductions in CRP\/hsCRP or IL\u20106, while the primary TNF\u2010\u03b1 finding was modest although its prediction interval crossed the null. Substantial heterogeneity, wide prediction intervals, and very low certainty of evidence limit clinical interpretation.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      PROSPERO number: CRD420261298312\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71382","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:01:37Z","timestamp":1790650897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Sodium\u2010Glucose Cotransporter\u20102 Inhibitors on Inflammatory Biomarkers: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1297-0675","authenticated-orcid":false,"given":"Mehmet","family":"Kanbay","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Nephrology Koc University School of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ermeena","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Medicine Koc University School of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama","family":"Al\u2010Shiab","sequence":"additional","affiliation":[{"name":"Department of Medicine Koc University School of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aladin","family":"Rustamov","sequence":"additional","affiliation":[{"name":"Department of Medicine Koc University School of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sedat","family":"Ay","sequence":"additional","affiliation":[{"name":"Department of Medicine Koc University School of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Guldan","sequence":"additional","affiliation":[{"name":"Department of Medicine Koc University School of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2235-0103","authenticated-orcid":false,"given":"Katherine R.","family":"Tuttle","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Kidney Research Institute University of Washington School of Medicine  Seattle Washington USA"},{"name":"Providence Medical Research Center Providence Inland Northwest Health  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mallamaci","sequence":"additional","affiliation":[{"name":"Associazione Ipertensione, Nefrologia Trapianto (IPNET) c\/o Nefrologia, Grande Ospedale Metropolitano  Reggio Calabria Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Zoccali","sequence":"additional","affiliation":[{"name":"Associazione Ipertensione, Nefrologia Trapianto (IPNET) c\/o Nefrologia, Grande Ospedale Metropolitano  Reggio Calabria Italy"},{"name":"Renal Research Institute  New York City New York USA"},{"name":"Institute of Molecular Biology and Genetics (Biogem)  Ariano Irpino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"6917","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nature01323","article-title":"Inflammation in Atherosclerosis","volume":"420","author":"Libby P.","year":"2002","journal-title":"Nature"},{"issue":"4","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1046\/j.1365-2796.2002.01019.x","article-title":"Inflammatory Bio\u2010Markers and Cardiovascular Risk Prediction","volume":"252","author":"Blake G. 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A.","year":"2024","journal-title":"Kidney International Reports"},{"issue":"1","key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1038\/s41467-020-15983-6","article-title":"SGLT2 Inhibition Modulates NLRP3 Inflammasome Activity via Ketones and Insulin in Diabetes With Cardiovascular Disease","volume":"11","author":"Kim S. R.","year":"2020","journal-title":"Nature Communications"},{"issue":"3","key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nm.3804","article-title":"The Ketone Metabolite \u03b2\u2010Hydroxybutyrate Blocks NLRP3 Inflammasome\u2013Mediated Inflammatory Disease","volume":"21","author":"Youm Y.\u2010H.","year":"2015","journal-title":"Nature Medicine"},{"issue":"12","key":"e_1_2_12_12_1","doi-asserted-by":"crossref","first-page":"107723","DOI":"10.1016\/j.jdiacomp.2020.107723","article-title":"Anti\u2010Inflammatory Properties of Antidiabetic Drugs: A \u201cPromised Land\u201d in the COVID\u201019 Era?","volume":"34","author":"Katsiki N.","year":"2020","journal-title":"Journal of Diabetes and Its Complications"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"1008922","DOI":"10.3389\/fcvm.2022.1008922","article-title":"Anti\u2010Inflammatory Role of SGLT2 Inhibitors as Part of Their Anti\u2010Atherosclerotic Activity: Data From Basic Science and Clinical Trials","volume":"9","author":"Scisciola L.","year":"2022","journal-title":"Frontiers in Cardiovascular Medicine"},{"issue":"4","key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.3390\/ijms26041670","article-title":"Anti\u2010Inflammatory Effects of SGLT2 Inhibitors: Focus on Macrophages","volume":"26","author":"Rykova E. 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H.","year":"2020","journal-title":"Diabetes Research and Clinical Practice"},{"key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"1045235","DOI":"10.3389\/fphar.2022.1045235","article-title":"The Effect of Sodium\u2010Glucose Cotransporter 2 Inhibitors on Biomarkers of Inflammation: A Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials","volume":"13","author":"Wang D.","year":"2022","journal-title":"Frontiers in Pharmacology"},{"issue":"1","key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s12902-023-01512-1","article-title":"The Effect of Sodium\u2010Glucose Co\u2010Transporter\u20102 (SGLT2) Inhibitors on Blood Interleukin\u20106 Concentration: A Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials","volume":"23","author":"Gohari S.","year":"2023","journal-title":"BMC Endocrine Disorders"},{"issue":"7","key":"e_1_2_12_18_1","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1111\/dom.15586","article-title":"The Effect of Sodium\u2010Glucose Cotransporter\u20102 Inhibitors on Inflammatory Biomarkers: A Meta\u2010Analysis of Randomized Controlled Trials","volume":"26","author":"Buttice L.","year":"2024","journal-title":"Diabetes, Obesity & Metabolism"},{"key":"e_1_2_12_19_1","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page M. 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W.","year":"2018","journal-title":"Diabetologia"},{"key":"e_1_2_12_29_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.metabol.2018.02.002","article-title":"Effects of Canagliflozin Versus Glimepiride on Adipokines and Inflammatory Biomarkers in Type 2 Diabetes","volume":"85","author":"Garvey W. T.","year":"2018","journal-title":"Metabolism, Clinical and Experimental"},{"issue":"7","key":"e_1_2_12_30_1","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1007\/s00125-019-4859-4","article-title":"Canagliflozin Reduces Inflammation and Fibrosis Biomarkers: A Potential Mechanism of Action for Beneficial Effects of SGLT2 Inhibitors in Diabetic Kidney Disease","volume":"62","author":"Heerspink H. J. L.","year":"2019","journal-title":"Diabetologia"},{"issue":"8","key":"e_1_2_12_31_1","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1177\/02676591221127924","article-title":"A Study of the Efficacy of Sacubitril\/Valsartan Plus Dapagliflozin Combination Treatment in Pulmonary Arterial Hypertension due to Left Heart Disease","volume":"38","author":"Ge T.","year":"2023","journal-title":"Perfusion"},{"issue":"1","key":"e_1_2_12_32_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s13098-022-00951-5","article-title":"The Effect of EMPAgliflozin on Markers of Inflammation in Patients With Concomitant Type 2 Diabetes Mellitus and Coronary ARtery Disease: The EMPA\u2010CARD Randomized Controlled Trial","volume":"14","author":"Gohari S.","year":"2022","journal-title":"Diabetology and Metabolic Syndrome"},{"key":"e_1_2_12_33_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13098-018-0395-5","article-title":"Anti\u2010Inflammatory Effects of Empagliflozin in Patients With Type 2 Diabetes and Insulin Resistance","volume":"10","author":"Hattori S.","year":"2018","journal-title":"Diabetology and Metabolic Syndrome"},{"issue":"1","key":"e_1_2_12_34_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13098-022-00815-y","article-title":"The Clinical Efficacy and Safety of Dapagliflozin in Patients With Diabetic Nephropathy","volume":"14","author":"Huang Y.","year":"2022","journal-title":"Diabetology & Metabolic Syndrome"},{"key":"e_1_2_12_35_1","doi-asserted-by":"crossref","first-page":"112926","DOI":"10.1016\/j.exger.2025.112926","article-title":"Effects of Dapagliflozin on Ventricular Remodeling and Prognosis in Older Females With Heart Failure With Preserved Ejection Fraction: A Single\u2010Center Prospective Study","volume":"211","author":"Huang J.","year":"2025","journal-title":"Experimental Gerontology"},{"key":"e_1_2_12_36_1","first-page":"4573","article-title":"Study of Anti\u2010Inflammatory Effects of Dapagliflozin as Add on Treatment Versus Metformin With Placebo Among Diabetic Patients in Thi\u2010Qar City, South of Iraq","volume":"12","author":"Hussein M. A. M.","year":"2020","journal-title":"International Journal of Pharmaceutical Research"},{"issue":"1","key":"e_1_2_12_37_1","first-page":"6796470","article-title":"Empagliflozin\u2010Metformin Combination Has Antioxidative and Anti\u2010Inflammatory Properties That Correlate With Vascular Protection in Adults With Type 1 Diabetes","volume":"2022","author":"Jani\u0107 M.","year":"2022","journal-title":"Journal Diabetes Research"},{"issue":"6","key":"e_1_2_12_38_1","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1111\/cen.13968","article-title":"Effects of Empagliflozin on Metabolic Parameters in Polycystic Ovary Syndrome: A Randomized Controlled Study","volume":"90","author":"Javed Z.","year":"2019","journal-title":"Clinical Endocrinology"},{"issue":"2","key":"e_1_2_12_39_1","first-page":"176","article-title":"SGLT2 Inhibitor\u2010Induced Ketonemia and Its Related Metabolic and Anti\u2010Inflammatory Impacts in Adult Patients With Type 2 Diabetes","volume":"19","author":"Karimi F.","year":"2023","journal-title":"Iranian Journal of Pharmaceutical Sciences"},{"issue":"1","key":"e_1_2_12_40_1","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12933-020-01079-4","article-title":"Tofogliflozin Does Not Delay Progression of Carotid Atherosclerosis in Patients With Type 2 Diabetes: A Prospective, Randomized, Open\u2010Label, Parallel\u2010Group Comparative Study","volume":"19","author":"Katakami N.","year":"2020","journal-title":"Cardiovascular Diabetology"},{"issue":"11","key":"e_1_2_12_41_1","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.2337\/dc22-0866","article-title":"Interleukin\u20106 and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes: New Insights From CANVAS","volume":"45","author":"Koshino A.","year":"2022","journal-title":"Diabetes Care"},{"issue":"1","key":"e_1_2_12_42_1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1186\/s12933-023-02027-8","article-title":"Effects of Dapagliflozin and Dapagliflozin\u2010Saxagliptin on Erythropoiesis, Iron and Inflammation Markers in Patients With Type 2 Diabetes and Chronic Kidney Disease: Data From the DELIGHT Trial","volume":"22","author":"Koshino A.","year":"2023","journal-title":"Cardiovascular Diabetology"},{"issue":"5","key":"e_1_2_12_43_1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.2337\/dc18-1569","article-title":"The SGLT2 Inhibitor Dapagliflozin Reduces Liver Fat but Does Not Affect Tissue Insulin Sensitivity: A Randomized, Double\u2010Blind, Placebo\u2010Controlled Study With 8\u2010Week Treatment in Type 2 Diabetes Patients","volume":"42","author":"Latva\u2010Rasku A.","year":"2019","journal-title":"Diabetes Care"},{"key":"e_1_2_12_44_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.hrtlng.2025.05.010","article-title":"Effect of SGLT2 Inhibitors on Inflammatory Markers and Oxygen Consumption in Non\u2010Diabetic Patients With STEMI Undergoing Primary PCI: A Parallel Design Single Blind Controlled Trial","volume":"73","author":"Li H.","year":"2025","journal-title":"Heart & Lung"},{"issue":"1","key":"e_1_2_12_45_1","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/s12967-025-06312-w","article-title":"Unveiling the Benefits of Vitamin D3 With SGLT\u20102 Inhibitors for Hypertensive Obese Obstructive Sleep Apnea Patients","volume":"23","author":"Loh H. 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