{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T06:00:16Z","timestamp":1772517616373,"version":"3.50.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"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>Objective<\/jats:title>\n                    <jats:p>This study aims to reorganize randomized controlled trials (RCTs) of traditional Chinese medicine (TCM) for adults with type 2 diabetes mellitus (T2DM) and metabolic-associated steatotic liver disease (MASLD; including legacy NAFLD) into a clinical evidence-anchored knowledge graph (KG) and harmonize effect semantics (\u201cunified effects\u201d) to support endpoint- and design-aware evidence navigation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically reviewed RCTs (2015\u20132025). Effect direction and scale were unified using a prespecified rule (treatment effect [TE] &amp;gt;0 indicates improvement). The prespecified primary endpoints maximizing cross-trial comparability were alanine aminotransferase (ALT), triglycerides (TG), Homeostatic Model Assessment of Insulin resistance (HOMA-IR), and controlled attenuation parameter (CAP); aspartate aminotransferase (AST) was retained for robustness. Metabolic endpoints were synthesized at the 12-week timepoint, while imaging endpoints (CAP and liver stiffness measurement [LSM]) were synthesized within a prespecified 8- to 24-week window. Trials were stratified as add-on versus mixed, with primary efficacy inferences based on add-on trials with balanced background Western medicine. Evidence was synthesized using REML-based random-effects meta-analysis (reporting prediction intervals) and weighted meta-regression. Risk of bias was assessed using RoB 2 and certainty of evidence using GRADE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 95 trials were included (\n                      <jats:italic>n<\/jats:italic>\n                      = 8,813; follow-up 2\u201348 weeks; predominantly add-on). The KG linked intervention categories (classic formulas, custom formulas, and Chinese patent medicines) to recurrent syndrome\/symptom patterns;\n                      <jats:italic>Salvia miltiorrhiza<\/jats:italic>\n                      emerged as a central herb-layer hub. In add-on trials, pooled effects for ALT, AST, HOMA-IR, and TG were directionally favorable, but heterogeneity was substantial and prediction intervals for biochemical endpoints were often wide and crossed the null. CAP showed a comparatively more reproducible short-term imaging signal than LSM. Meta-regression suggested hypothesis-generating design patterns in which estimate stability tended to improve with larger per-arm sample sizes (\u2248\u226540\u201350) and longer follow-up (\u2248\u226512\u201316 weeks). RoB 2 ratings were predominantly \u201csome concerns,\u201d and GRADE certainty was commonly downgraded for inconsistency and\/or imprecision.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In adults with T2DM and MASLD, add-on trials show directionally favorable pooled biochemical\/metabolic changes after unified effect harmonization, but uncertainty remains substantial. CAP may be a more reproducible short-term imaging endpoint than LSM. Evidence-derived design patterns should be interpreted as hypothesis-generating rather than causal thresholds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n                      , identifier CRD420251167450.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1740126","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T05:22:53Z","timestamp":1772515373000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Traditional Chinese medicine for type 2 diabetes with metabolic-associated steatotic liver disease: unified effects and design thresholds"],"prefix":"10.3389","volume":"17","author":[{"given":"Youfang","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibi","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liting","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haozhe","family":"Xiong","sequence":"additional","affiliation":[{"name":"China\u2013Japan Friendship Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.06.003","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"79","author":"Rinella","year":"2023","journal-title":"J Hepatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(24)00318-8","article-title":"Metabolic dysfunction-associated steatotic liver disease: heterogeneous pathomechanisms and effectiveness of metabolism-based treatment","volume":"13","author":"Stefan","year":"2024","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1186\/s12933-025-02824-3","article-title":"Association of temporal MASLD with type 2 diabetes, cardiovascular disease and mortality","volume":"24","author":"Han","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000913","article-title":"Epidemiology, screening, and co-management of type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease","volume":"83","author":"Qi","year":"2024","journal-title":"Hepatology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(23)00187-5","article-title":"NAFLD and liver-related events: does type 2 diabetes have a key role","volume":"8","author":"Vilar-Gomez","year":"2023","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2337\/dci24-0094","article-title":"Metabolic dysfunction-associated steatotic liver disease (MASLD) in people with diabetes: the need for screening and early intervention. 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