{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:09:59Z","timestamp":1789160999082,"version":"build-2803163510"},"reference-count":52,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T00:00:00Z","timestamp":1604016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Ministero della Salute Bando Ricerca Finalizzata","award":["RF-2011-02346959"],"award-info":[{"award-number":["RF-2011-02346959"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aim<\/jats:title>\n                  <jats:p>The aim of this study was to investigate whether treatment with rapamycin plus vildagliptin restores \u03b2-cell function in patients with long-standing type 1 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A phase 2, single-center, randomized, double-blind, placebo-controlled study was conducted in long-standing type 1 diabetes patients randomly assigned (1:1:1) to 4 weeks of rapamycin (group 2), 4 weeks of rapamycin plus 12 weeks of vildagliptin (group 3), or double placebo (group 1). The primary outcome was the proportion of participants with a positive response to the Mixed-Meal Tolerance Test (C-peptide at 90 minutes\u2005&amp;gt;\u20050.2 nmol\/L) at weeks 4 and 12. Secondary end points included insulin requirement, standard measures of glycemic control, and hormonal and immunological profile.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Fifty-five patients were randomly assigned to group 1 (n\u2005=\u200518), group 2 (n\u2005=\u200519), or group 3 (n\u2005=\u200518). No patient in any group showed a positive C-peptide response, and there was no significant difference at 4 and 12 weeks for the primary outcome. At 4 weeks, insulin requirement decreased from 0.54 to 0.48 U\/kg\/day in group 2 (P\u2005=\u2005.013), from 0.59 to 0.51 U\/kg\/day in group 3 (P\u2005&amp;lt;\u2005.001), whereas it did not change in group 1. At 12 weeks, glycated hemoglobin significantly decreased both in group 2 (from 7.3% [56 mmol\/mol] to 7% [53 mmol\/mol]; P\u2005=\u2005.045] and in group 3 (from 7.2% [55.5 mmol\/mol] to 6.9% [52 mmol\/mol]; P\u2005=\u2005.001]. Rapamycin treatment was associated with a decrease in insulin antibody titer and changes in hormonal\/immunological profile.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Rapamycin reduced insulin requirement, but did not restore \u03b2-cell function in patients with long-standing type 1 diabetes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa791","type":"journal-article","created":{"date-parts":[[2020,10,30]],"date-time":"2020-10-30T10:10:56Z","timestamp":1604052656000},"page":"e507-e519","source":"Crossref","is-referenced-by-count":19,"title":["Rapamycin Plus Vildagliptin to Recover \u03b2-Cell Function in Long-Standing Type 1 Diabetes: A Double-Blind, Randomized Trial"],"prefix":"10.1210","volume":"106","author":[{"given":"Andrea Mario","family":"Bolla","sequence":"first","affiliation":[{"name":"San Raffaele Diabetes Research Institute, IRCCS Ospedale San 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