{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:42:01Z","timestamp":1792514521886,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To investigate the association between sodium-glucose cotransporter 2 inhibitors (SGLT2i) use and diabetic retinopathy (DR) progression, and to explore supporting genetic and molecular evidence using a retrospective cohort study with Mendelian randomization (MR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>In this retrospective cohort study at Shandong Provincial Hospital from January 2023 to December 2024, patients with type 2 diabetes on stable SGLT2i plus basal insulin (SGLT2i+INS) or sulfonylureas plus basal insulin (SUL+INS) were included. Wide-field swept-source optical coherence tomography angiography (SS-OCTA) was used to assess retinal microvascular parameters. Kaplan\u2013Meier and Cox regression analyses evaluated DR progression and new-onset diabetic macular edema with sensitivity analyses performed to assess robustness. An exploratory nomogram was developed and evaluated by decision curve analysis. Two-sample MR and two-step mediation analyses were conducted to examine the genetic association between SGLT2 and DR and to identify potential mediating metabolites and plasma proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 191 eyes were included: 56 in the SGLT2i+INS group and 135 in the SUL+INS group. SGLT2i+INS was associated with a lower risk of DR progression (HR\u00a0=\u00a00.40, 95% CI 0.19\u20130.84; P\u00a0=\u00a00.016) and reduced cumulative incidence (log-rank P\u00a0=\u00a00.032). The exploratory OCTA-based nomogram showed modest performance (C-index=0.705). MR supported an association between genetically proxied SGLT2 and DR risk (OR\u00a0=\u00a01.21, 95% CI 1.05\u20131.39; P\u00a0=\u00a00.009). Nine metabolites and five plasma proteins showed nominal evidence of potential mediation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among insulin-treated patients with type 2 diabetes, SGLT2i use was associated with a lower risk of DR progression than sulfonylurea use. OCTA parameters and candidate molecular mediators may provide exploratory prognostic and biological insights, warranting validation in larger prospective studies and randomized trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1846454","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:20:40Z","timestamp":1784175640000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["SGLT2 inhibitors and diabetic retinopathy progression: evidence from a retrospective cohort study and Mendelian randomization analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Mengya","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Shandong Provincial Hospital, Shandong University","place":["Jinan, Shandong, China"]},{"name":"Department of Ophthalmology, Shandong Second Provincial General Hospital","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second People\u2019s Hospital of Jinan","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shandong Provincial Hospital, Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2021.04.027","article-title":"Global prevalence of diabetic retinopathy and projection of burden through 2045: Systematic review and meta-analysis","volume":"128","author":"Teo","year":"2021","journal-title":"Ophthalmology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/cpt.3074","article-title":"Risk of diabetic retinopathy in patients with type 2 diabetes after SGLT-2 inhibitors: A nationwide population cohort study","volume":"115","author":"Huang","year":"2024","journal-title":"Clin Pharmacol Ther"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2022.114829","article-title":"Redox signaling in diabetic retinopathy and opportunity for therapeutic intervention through natural products","volume":"244","author":"Wang","year":"2022","journal-title":"Eur J Med Chem"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.eprac.2023.02.001","article-title":"American Association of Clinical Endocrinology consensus statement: Comprehensive type 2 diabetes management algorithm - 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