{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:29:49Z","timestamp":1791901789474,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Multiple pharmacologic therapies reduce chronic kidney disease (CKD) progression in patients with diabetes; however, the absence of head\u2010to\u2010head trials and heterogeneity across studies limits the interpretation of indirect comparisons. We evaluated class\u2010level treatment effects within a predominantly placebo\u2010centred evidence network.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic review and class\u2010level frequentist random\u2010effects network meta\u2010analysis of randomised controlled trials evaluating major pharmacologic therapy classes for CKD progression in patients with diabetes. The primary outcome was CKD progression, defined according to the principal composite kidney endpoint reported in each trial. Exploratory analyses evaluated albuminuria reduction and trial\u2010level surrogate associations between albuminuria and clinical kidney outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nine trials involving 37,749 participants were included. The evidence network was star\u2010shaped with placebo as the central comparator. All therapeutic classes were associated with reduced CKD progression compared with placebo. Sodium\u2010glucose cotransporter\u20102 inhibitors (SGLT2i) demonstrated the most precise estimate (HR 0.66, 95% CI 0.60\u20130.74) and were supported by high\u2010confidence evidence. Confidence in placebo\u2010referenced estimates for other therapeutic classes ranged from moderate to low because of indirectness, limited trial numbers and differences in study design and patient populations. Findings were generally consistent across sensitivity analyses. No significant association was observed between treatment\u2010induced albuminuria reduction and clinical kidney outcomes (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.007), although interpretation was limited by ecological bias and the small number of included studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Multiple pharmacologic classes were associated with reduced CKD progression compared with placebo in patients with diabetes. Among placebo\u2010referenced comparisons, the most consistent and highest\u2010confidence estimates were observed for SGLT2i. However, the predominantly placebo\u2010centred network, absence of direct active\u2010comparator trials and important transitivity concerns limit inference regarding comparative efficacy among therapies. Findings should therefore be interpreted as placebo\u2010referenced class\u2010level treatment effects rather than evidence of comparative superiority. Direct comparative effectiveness and combination\u2010therapy trials are needed to define optimal treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70285","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:58:41Z","timestamp":1784271521000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Placebo\u2010Referenced Class\u2010Level Treatment Effects on Chronic Kidney Disease Progression in Patients With Diabetes: A Network Meta\u2010Analysis"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7355-9532","authenticated-orcid":false,"given":"Ravi Kumar","family":"Pandey","sequence":"first","affiliation":[{"name":"Nepalgunj Medical College  Nepalgunj Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0166-1412","authenticated-orcid":false,"given":"Maryam","family":"Imran","sequence":"additional","affiliation":[{"name":"Fatima Jinnah Medical University  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1299-9045","authenticated-orcid":false,"given":"Ishba","family":"Manal","sequence":"additional","affiliation":[{"name":"Dow University of Health Sciences  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9603-6166","authenticated-orcid":false,"given":"Muhammad","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Sharif Medical City  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5376-2437","authenticated-orcid":false,"given":"Aliya","family":"Noor","sequence":"additional","affiliation":[{"name":"King Edward Medical University  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9986-3495","authenticated-orcid":false,"given":"Ali","family":"Rohan","sequence":"additional","affiliation":[{"name":"The University of Lahore, University College of Medicine and Dentistry  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2024.111884"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.06.008"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.15450"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010025\u201001171\u20103"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfae212"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2410659"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1811744"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024816"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204233"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025845"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110956"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2403347"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)30772\u2010X"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15765"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(23)00321\u20102"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.02.033"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab777"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvac054"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581\u2010021\u201000490\u20108"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15009"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2014.07.030"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2019.06.009"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011161"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011303"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.7326\/ANNALS\u201025\u201002117"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.10081"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(21)00243\u20106"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2025.20834"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.26230"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.071079"}],"container-title":["Endocrinology, 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