{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:57:08Z","timestamp":1778853428307,"version":"3.51.4"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"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><jats:title>Aim<\/jats:title><jats:p>In a recent randomized, multicenter trial (NCT02814838) a short-term anti-inflammatory treatment with ladarixin (LDX; an inhibitor of the CXCR1\/2 chemokine receptors) did not show benefit on preserving residual beta cell function in new-onset type 1 diabetes. We present a <jats:italic>post hoc<\/jats:italic> analysis of trial patients in the predefined subgroup analysis developed according to baseline daily insulin requirement (DIR) tertiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A double-blind, randomized (2:1), placebo-controlled study was conducted in 45 men and 31 women (aged 18\u201346\u2009years) within 100\u2009days of the first insulin administration. Patients received LDX (400\u2009mg twice daily) for three\u2009cycles of 14\u2009days on\/14\u2009days off, or placebo. The primary endpoint was the area under the curve for C-peptide [AUC (0\u2013120 min)] in response to a 2-h mixed meal tolerance test (MMTT) at week 13\u2009\u00b1\u20091. Seventy-five patients completed the week 13\u2009MMTT and were divided into three groups according to the DIR tertiles: lower, \u2264 0.23U\/kg\/die (n = 25); middle, 0.24\u20130.40 U\/kg\/die (n = 24); upper, \u2265 0.41 U\/kg\/die (n = 26).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>When considering the patients in the upper tertile (HIGH-DIR), C-peptide AUC (0\u2013120 min) at 13\u2009weeks was higher in the LDX group (n = 16) than in the placebo (n = 10) group [difference: 0.72 nmol\/L (95% CI 0.9\u20131.34), p = 0.027]. This difference reduced over time (0.71 nmol\/L at 26 weeks, p = 0.04; 0.42 nmol\/L at 52 weeks, p = 0.29), while it has never been significant at any time in patients in the lower and\/or middle tertile (LOW-DIR). We characterized at baseline the HIGH-DIR and found that endo-metabolic (HOMA-B, adiponectin, and glucagon-to-C-peptide ratio) and immunologic (chemokine (C-C motif) ligand 2 (CCL2)\/monocyte chemoattractant protein 1 (MCP1) and Vascular Endothelial Growth Factor (VEGF)) features distinguished this group from LOW-DIR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>While LDX did not prevent the progressive loss of beta-cell function in the majority of treated subjects, the <jats:italic>post hoc<\/jats:italic> analysis suggests that it could work in subjects with HIGH-DIR at baseline. As we found differences in endo-metabolic and immunologic parameters within this subgroup, this generates the hypothesis that the interactions between host factors and drug action can contribute to its efficacy. Further research is needed to evaluate this hypothesis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1175640","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T10:25:15Z","timestamp":1687256715000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Post hoc analysis of a randomized, double-blind, prospective trial evaluating a CXCR1\/2 inhibitor in new-onset type 1 diabetes: endo-metabolic features at baseline identify a subgroup of 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