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We aimed to review the clinical impact of SGLT2i and GLP1-ra therapy on the risk of diabetic retinopathy and diabetic macular oedema in individuals with type 2 diabetes taking insulin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This is a retrospective cohort analysis of approximately two million people with type 2 diabetes receiving insulin across 97 healthcare organisations using a global federated health research network (TriNetX, Cambridge, USA). Two intervention cohorts (SGLT2i + insulin,\n                      <jats:italic>n<\/jats:italic>\n                      =176,409; GLP1-ra + insulin,\n                      <jats:italic>n<\/jats:italic>\n                      =207,034) were compared against a control cohort (insulin with no SGLT2i\/GLP1-ra,\n                      <jats:italic>n<\/jats:italic>\n                      =1,922,312). Kaplan\u2013Meier survival analysis was performed and estimated HRs were reported for each outcome. Propensity score was used to 1:1 match for age, sex, ischaemic heart disease, hypertension, microvascular complications, chronic kidney disease, HbA\n                      <jats:sub>1c<\/jats:sub>\n                      , BMI and use of pioglitazone, lipid modifying agents, antilipemic agents, ACE inhibitors, angiotensin II inhibitors and metformin. A sub-analysis comparing the two intervention cohorts was also performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SGLT2i with insulin was associated with a reduced HR (95% CI) for diabetic macular oedema compared with the control cohort (0.835; 0.780, 0.893), while GLP1-ra with insulin demonstrated a lack of signal with no statistical significance to the HR (1.013; 0.960, 1.069). SGLT2i with insulin was not associated with a clinically significant increase in the risk of developing diabetic retinopathy (1.076; 1.027, 1.127), while GLP1-ra with insulin increased diabetic retinopathy risk (1.308; 1.261, 1.357). Compared with SGLT2i with insulin, GLP1-ra with insulin was associated with higher risk of diabetic retinopathy (1.205; 1.153, 1.259) and diabetic macular oedema (1.130; 1.056, 1.208).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Our study suggests that the combination of SGLT2i and insulin is associated with lower risk of developing diabetic macular oedema. However, the use of GLP1-ra was associated with an increased risk of diabetic retinopathy in individuals with type 2 diabetes also taking insulin. A comparative analysis showed favourable outcomes with SGLT2i and insulin in the development of diabetic macular oedema and diabetic retinopathy. RCTs using dedicated\u00a0 retinal imaging are required to determine the causal relationship with these therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-024-06132-5","type":"journal-article","created":{"date-parts":[[2024,4,7]],"date-time":"2024-04-07T23:10:07Z","timestamp":1712531407000},"page":"1271-1282","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Risk of diabetic retinopathy and diabetic macular oedema with sodium\u2013glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database"],"prefix":"10.1007","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7290-8523","authenticated-orcid":false,"given":"Aikaterini","family":"Eleftheriadou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0905-6524","authenticated-orcid":false,"given":"David","family":"Riley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3558-7353","authenticated-orcid":false,"given":"Sizheng S.","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8855-220X","authenticated-orcid":false,"given":"Philip","family":"Austin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4832-455X","authenticated-orcid":false,"given":"Gema","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory Y. 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Available from https:\/\/classic.clinicaltrials.gov\/ct2\/show\/NCT03811561, accessed 15 Oct 2023"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-024-06132-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-024-06132-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-024-06132-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T04:03:08Z","timestamp":1717560188000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-024-06132-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,8]]},"references-count":43,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["6132"],"URL":"https:\/\/doi.org\/10.1007\/s00125-024-06132-5","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,8]]},"assertion":[{"value":"15 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Some of the data were presented as an abstract at the 59th EASD Annual Meeting in 2023. No data from Liverpool University NHS Foundation Trust was used in this analysis.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"To gain access to the data in the TriNetX research network, a request can be made to TriNetX (\n                      \n                      ), but costs may be incurred, a data sharing agreement would be necessary and no patient identifiable information can be obtained.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"PA and GH are employees of TriNetX. UA has received honoraria from Viatris, Gr\u00fcnenthal, Eli Lilly, Procter & Gamble, and Sanofi for educational meetings and has received investigator-led funding form Proctor & Gamble. GYHL is a speaker for BMS\/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo and Anthem. No fees are received personally. He is also a co-principal investigator of the AFFIRMO project on multi-morbidity in atrial fibrillation, which has received funding from the European Union\u2019s Horizon 2020 research and innovation programme under grant agreement No. 899871. TLJ is a consultant\/advisor to Opthea, 2CTech, iLumen, solicitors acting for Regeneron, Appellis, PHMR and DORC. His team, in the KORU unit, receives free use of equipment for non-commercial trials he leads from KCL, and previously from Zeiss. JPHW reports consultancy\/advisory board work for the pharmaceutical industry contracted via the University of Liverpool (no personal payment) for Altimmune, AstraZeneca, Boehringer Ingelheim, Cytoki, Lilly, Napp, Novo Nordisk, Menarini, Pfizer, Rhythm Pharmaceuticals, Sanofi, Saniona, Tern, Shionogi and Ysopia; research grants for clinical trials from AstraZeneca and Novo Nordisk; and personal honoraria\/lecture fees from AstraZeneca, Boehringer Ingelheim, Medscape, Napp, Novo Nordisk and Rhythm. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"All authors contributed to the conception and the writing of the manuscript. AE interpreted the data and wrote the first version of the manuscript. AE and UA edited the manuscript. DR, PA and GH contributed to the study design. DR was responsible for the data analysis. SSZ, PA and GH facilitated the statistical analyses. DR, SSZ, GH, GYHL, JPHW, TLJ and UA contributed to data interpretation. DR, GYHL, JPHW, TLJ and UA reviewed the manuscript and contributed to the discussion. All authors reviewed and approved the final version of the manuscript to be published. UA is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}