{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:33:30Z","timestamp":1790800410231,"version":"4.1.0"},"reference-count":174,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Emerging evidence suggests that vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors exert synergistic immunomodulatory, anti-inflammatory and antioxidant actions. Moreover, intervention studies showed that combination therapy based on the concomitant use of vitamin D and DPP-4 inhibitors (VIDPP-4i) may preserve beta-cell function in patients with type 1 diabetes mellitus (T1D) and latent autoimmune diabetes in adults (LADA). These effects are particularly relevant in the context of beta-cell replacement strategies, whose long-term efficacy can be hampered by various factors, such as immune-mediated graft rejection, inadequate vascularization, hypoxia, trauma-induced cell apoptosis, fibrosis, host immune response, and recurrence of autoimmunity. Based on preclinical and clinical studies conducted in the fields of autoimmune diabetes and solid organ\/cell transplantation, the present narrative review aims to describe the rationale behind the investigation of VIDPP-4i combination therapy as an adjuvant treatment strategy to enhance the efficacy of novel beta-cell replacement therapies for T1D. In this regard, we discuss the potential immune and metabolic mechanisms through which vitamin D and DPP-4 inhibitors can promote the long-term function and survival of transplanted islets in patients with T1D receiving various types of beta-cell replacement therapies, including therapeutic approaches using encapsulated stem cell-derived beta cells.<\/jats:p>","DOI":"10.3390\/medsci13030141","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T11:31:37Z","timestamp":1755516697000},"page":"141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Combined Use of Vitamin D and DPP-4 Inhibitors as a Potential Adjuvant Treatment Strategy to Enhance the Efficacy of Novel Beta-Cell Replacement Therapies for Type 1 Diabetes"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3287-0476","authenticated-orcid":false,"given":"Marcelo Maia","family":"Pinheiro","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Centro Universit\u00e1rio de V\u00e1rzea Grande, UNIVAG, Av. Dom Orlando Chaves 2655-Cristo Rei, V\u00e1rzea Grande 78118-000, Mato Grosso, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe Moura Maia","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, UNIC\u2014Universidade de Cuiab\u00e1, Av. Manoel Jos\u00e9 de Arruda 3100-Jardim Europa, Cuiab\u00e1 78065-900, Mato Grosso, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3155-7429","authenticated-orcid":false,"given":"Bruna Fioravante","family":"Di Serio","sequence":"additional","affiliation":[{"name":"Beta Cell Center, R. das Papoulas 332, Cuiab\u00e1 78043-138, Mato Grosso, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7177-1107","authenticated-orcid":false,"given":"Nathalia","family":"Padilla","sequence":"additional","affiliation":[{"name":"Division of Cellular Transplantation, Department of Surgery, Cell Transplant Center, Diabetes Research Institute (DRI), University of Miami Miller School of Medicine, 1450 NW 10th Ave., Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2212-0276","authenticated-orcid":false,"given":"Benjamin Udoka","family":"Nwosu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Pediatrics, Zucker School of Medicine at Hofstra\/Northwell, 500 Hofstra Blvd, Hempstead, NY 11549, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Della-Morte","sequence":"additional","affiliation":[{"name":"Section of Clinical Nutrition and Nutrigenomics, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy"},{"name":"Department of Neurology, Evelyn F. McKnight Brain Institute, University of Miami Miller School of Medicine, 1120 NW 14th Street, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camillo","family":"Ricordi","sequence":"additional","affiliation":[{"name":"Division of Cellular Transplantation, Department of Surgery, Cell Transplant Center, Diabetes Research Institute (DRI), University of Miami Miller School of Medicine, 1450 NW 10th Ave., Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2032-8735","authenticated-orcid":false,"given":"Marco","family":"Infante","sequence":"additional","affiliation":[{"name":"Division of Cellular Transplantation, Department of Surgery, Cell Transplant Center, Diabetes Research Institute (DRI), University of Miami Miller School of Medicine, 1450 NW 10th Ave., Miami, FL 33136, USA"},{"name":"Section of Diabetes & Metabolic Disorders, UniCamillus\u2014Saint Camillus International University of Health Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0140-6736(13)60591-7","article-title":"Type 1 diabetes","volume":"383","author":"Atkinson","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.20517\/mtod.2024.12","article-title":"Prevention and treatment of type 1 diabetes: In search of the ideal combination therapy targeting multiple immunometabolic pathways","volume":"4","author":"Pinheiro","year":"2024","journal-title":"Metab. 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