{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:41:32Z","timestamp":1773207692464,"version":"3.50.1"},"reference-count":102,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Type 1 diabetes accounts for approximately 10% of all diabetes cases, meaning that a substantial number of patients require lifelong insulin therapy. Although many individuals adapt to the demands of daily injections, they remain vulnerable to hypoglycaemia and long\u2010term complications, particularly when glycaemic control is suboptimal. These persistent challenges have driven the search for effective treatments that may improve quality of life and potentially induce clinical remission. To address this need, we conducted a Bayesian network meta\u2010analysis to evaluate the capacity of non\u2010insulin therapies to preserve pancreatic \u03b2\u2010cell function in type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library for studies published between 1 January 2000 and 1 March 2025. The search included randomised controlled trials (RCTs) and non\u2010randomised controlled trials (nRCTs) that evaluated non\u2010insulin interventions such as stem cell transplantation (SCT), Janus kinase inhibitors (JAK\/TKI), and monoclonal antibodies targeting T\u2010cell CD3 molecules (CD3\u2010Ab). The primary outcome measure was C\u2010peptide level, and the secondary outcome was HbA1c.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 68 studies were included in our analysis, comprising 69 trials (64 RCTs and 5 nRCTs) involving 4779 patients with type 1 diabetes. These trials evaluated 15 non\u2010insulin interventions in addition to conventional therapy (placebo). While most interventions showed superior results to placebo, only stem cell therapy (SCT) demonstrated significant C\u2010peptide level improvement (MD\u00a0=\u00a00.20; 95% CrI: 0.04\u20130.36). Although the other 13 interventions (including JAK\/TKI inhibitors and CD3 antibodies) produced positive mean differences, none of their 95% CrI contained 0, indicating a lack of statistical significance. In addition, anti\u2010thymocyte globulin (ATG) was associated with a slight negative mean difference (MD\u00a0=\u00a0\u22120.02; 95% CrI: \u22120.32 to 0.28), suggesting a potentially detrimental effect on islet function. Analyses using HbA1c as an outcome metric indicated that Vit (MD\u00a0=\u00a0\u22121.5; 95% CrI: \u22122.1 to \u22120.78) and Cyto\u2010Mod (MD\u00a0=\u00a0\u22120.72; 95% CrI: \u22121.4 to \u22120.12) conferred a relatively greater improvement in glycaemic control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although the clinical application of SCT is not yet fully mature, our meta\u2010analysis further confirmed the notable effect of SCT on islet function in patients with type 1 diabetes mellitus. However, analyses of HbA1c did not demonstrate a significant effect of SCT on glycaemic control. This may be due to fluctuations in blood glucose during the post\u2010transplantation recovery phase, which may have affected HbA1c measurements. A fully significant negative correlation between islet function and glycaemic control has not been observed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dmrr.70120","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:23:19Z","timestamp":1767698599000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Therapeutic Approach to Preserving or Reversing Pancreatic Islet Beta Cells in Patients With Type 1 Diabetes: A Bayesian Network Meta\u2010Analysis of Comparative Efficacy"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8056-8996","authenticated-orcid":false,"given":"Chen","family":"Zheng","sequence":"first","affiliation":[{"name":"The Third Clinical Medical College of Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sibiao","family":"Lu","sequence":"additional","affiliation":[{"name":"The Third Clinical Medical College of Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Qiang","sequence":"additional","affiliation":[{"name":"The Third Clinical Medical College of Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiale","family":"Xu","sequence":"additional","affiliation":[{"name":"The Third Clinical Medical College of Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Xu","sequence":"additional","affiliation":[{"name":"The Third Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(13)60591\u20107"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.10.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4203"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(23)00267\u2010x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201042581\u2010z"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102265.2008.03179.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2020.0305"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14730"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107157"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916\u2010025\u201004201\u2010z"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.283.15.2008"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13643\u2010018\u20100699\u20104"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i4919"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102288\u201013\u201035"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39489.470347.ad"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099682"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003082"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916\u2010021\u201002166\u20103"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2021.07.011"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/0272989x12455847"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf00399937"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(13)60023\u20109"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.12361"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2308743"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13\u20100327"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa012864"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.6.1763"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2009.04.007"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(11)60931\u20108"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.2337\/db13\u20100345"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010012\u20102753\u20104"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010009\u20101644\u20109"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010020\u201005317\u2010y"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09\u20101571"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2006136"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20236032"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac369"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.150074"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14770"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010024\u201003115\u20102"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.12072"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14\u20100656"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010023\u201005934\u20103"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15\u20100171"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2017.12.006"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010022\u201002941\u2010w"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010021\u201002417\u20103"},{"issue":"8","key":"e_1_2_9_49_1","first-page":"541","article-title":"The Effect of Fetal Liver\u2010Derived Cell Suspension Allotransplantation on Patients With Diabetes: First Year of follow\u2010up","volume":"50","author":"Ghodsi M.","year":"2012","journal-title":"Acta Medica Iranica"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.20945\/2359\u20103997000000368"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09\u20102297"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpediatrics.2012.164"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.7860\/JCDR\/2017\/27321.10645"},{"issue":"1","key":"e_1_2_9_54_1","first-page":"134","article-title":"Evaluation the Effect of Vitamin D3 on Glycemic Indices on Iraqi Children With Type 1 DM","volume":"42","author":"Nafei L. T.","year":"2017","journal-title":"International Journal of Pharmaceutical Sciences Review and Research"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.5114\/pedm.2018.80992"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvab179"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.1276"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc10\u20100814"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.08.002"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc18\u20100494"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(13)70065\u20102"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci78492"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.2064"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010018\u20100089\u20104"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc21\u20100318"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(21)00139\u2010x"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2306691"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13797"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001369\u20109"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab026"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa149"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(14)70115\u20109"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(11)60886\u20106"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(13)70111\u20106"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa0904452"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09\u20101349"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2004.12.003"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa0804328"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(11)60895\u20107"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1107096"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019\u201000481"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc\u20102020\u2010001523"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/pedi.13244"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf7779"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09\u20100449"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3006103"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.503"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010024\u201006290\u20106"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.4274\/jcrpe.981"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.3767"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1177\/0272989x12458724"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741\u20107015\u201011\u2010159"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1201"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dys041"},{"key":"e_1_2_9_95_1","volume-title":"Heterogeneity: Subgroups, Meta\u2010Regression, Bias and Bias\u2010Adjustment","author":"Dias S.","year":"2012"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj\u20102022\u2010074495"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d4002"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11\u20109998"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2011.04.014"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.09.004"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2864"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20101978\u20105"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.26444\/jpccr\/75145"}],"container-title":["Diabetes\/Metabolism Research and Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dmrr.70120","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/dmrr.70120","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dmrr.70120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T07:44:36Z","timestamp":1773128676000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dmrr.70120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":102,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/dmrr.70120"],"URL":"https:\/\/doi.org\/10.1002\/dmrr.70120","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/DMRR.70120\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/DMRR.70120\/v1\/decision1","asserted-by":"object"}]},"ISSN":["1520-7552","1520-7560"],"issn-type":[{"value":"1520-7552","type":"print"},{"value":"1520-7560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70120"}}