{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:05:54Z","timestamp":1789023954892,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"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":"ABSTRACT<\/jats:title>\n \n Aims<\/jats:title>\n To evaluate whether intravitreal ranibizumab (IVR) frequency is associated with longitudinal renal markers in diabetic macular oedema (DMO) and whether the expected systemic renal and haematological effects of SGLT2 inhibition are reproduced.<\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n In this post hoc sub\u2010analysis of the prospective COMET randomised controlled trial, 53 participants were analysed. The estimated glomerular filtration rate (eGFR), haematocrit (Hct), and urinary albumin\u2010to\u2010creatinine ratio (UACR) were assessed over 48\u2009weeks using linear mixed\u2010effects models with the treatment group, week, group\u2010by\u2010week interaction, and cumulative IVR as fixed effects.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Baseline eGFR was preserved (72.2\u2009\u00b1\u200918.5\u2009mL\/min\/1.73\u2009m\n 2<\/jats:sup>\n ) despite common albuminuria (median UACR 50.6\u2009mg\/gCr); mean cumulative IVR at week 48 was 7.00\u2009\u00b1\u20094.42. Cumulative IVR was not significantly associated with eGFR (\u22120.22\u2009mL\/min\/1.73\u2009m\n 2<\/jats:sup>\n per injection; 95% CI \u22120.59 to 0.15;\n p<\/jats:italic>\n \u2009=\u20090.25), ln(UACR), or Hct. The SGLT2 inhibitor reproduced an early eGFR dip and Hct rise.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n No statistically significant exposure\u2010response association was detected between cumulative IVR and renal markers within the COMET trial cohort and dosing range. Because all participants received IVR and the sample size was modest, small cumulative renal effects cannot be excluded.<\/jats:p>\n \n Trial Registration:<\/jats:bold>\n University Hospital Medical Information Network Center (UMIN000057674); Japan Registry of Clinical Trials (jRCTs031180210, parent COMET trial)\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.71314","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:06:48Z","timestamp":1789020408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Renal Safety of Intravitreal Ranibizumab and the Effects of\n SGLT2<\/scp>\n Inhibition in Diabetic Macular Oedema: A Post Hoc Analysis of the\n COMET<\/scp>\n Trial"],"prefix":"10.1111","author":[{"given":"Toshiki","family":"Sakai","sequence":"first","affiliation":[{"name":"Department of Nutrition and Metabolic Medicine Center for Preventive Medical Science, Chiba University Chiba Japan"},{"name":"Department of Medicine, Division of Diabetes, Endocrinology and Metabolism Kimitsu Chuo Hospital Kisarazu Japan"},{"name":"Department of Internal Medicine Minami\u2010Boso City Tomiyama National Health Insurance Hospital Minami\u2010Boso Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2535-5396","authenticated-orcid":false,"given":"Ryoichi","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Diabetes, Endocrinology and Metabolism Kimitsu Chuo Hospital Kisarazu Japan"},{"name":"Department of Endocrinology, Hematology and Gerontology Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7374-9993","authenticated-orcid":false,"given":"Masaya","family":"Koshizaka","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Metabolic Medicine Center for Preventive Medical Science, Chiba University Chiba Japan"},{"name":"Department of Endocrinology, Hematology and Gerontology Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Takatsuna","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Chiba Rosai Hospital Chiba Japan"},{"name":"Department of Ophthalmology and Vision Science Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Tatsumi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Vision Science Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Metabolic Medicine Center for Preventive Medical Science, Chiba University Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiro","family":"Maezawa","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hematology and Gerontology Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3033-4813","authenticated-orcid":false,"given":"Koutaro","family":"Yokote","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Hematology and Gerontology Chiba University Graduate School of Medicine Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.ophtha.2013.11.041","article-title":"Three\u2010Year Outcomes of Individualized Ranibizumab Treatment in Patients With Diabetic Macular Edema: The RESTORE Extension Study","volume":"121","author":"Schmidt\u2010Erfurth U.","year":"2014","journal-title":"Ophthalmology"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1001\/jama.2015.15217","article-title":"Panretinal Photocoagulation vs Intravitreal Ranibizumab for Proliferative Diabetic Retinopathy: A Randomised Clinical Trial","volume":"314","author":"Gross J. 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