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A single center parallel double-blind randomized clinical trial with 6\u00a0months of follow-up was performed in patients with persistent IGT after 12\u00a0months of treatment with metformin and lifestyle; patients were randomized to continue with metformin 850\u00a0mg twice daily (M group, n\u2009=\u200912) or linagliptin\/metformin 2.5\/850\u00a0mg twice daily (LM group, n\u2009=\u200919). Anthropometric measurements were obtained by standard methods and by bioelectrical impedance; glucose was measured by dry chemistry, insulin by chemiluminescence, and pancreatic \u03b2-cell function was calculated with the disposition index using glucose and insulin values during oral glucose tolerance test (OGTT) and adjusting by insulin sensitivity. The main outcomes were glucose levels during OGTT and pancreatic \u03b2-cell function. Patients in the LM group had a reduction in weight (\u22121.7\u2009\u00b1\u20090.6, p\u2009&lt;\u20090.05) and body mass index (BMI, \u22120.67\u2009\u00b1\u20090.2, p\u2009&lt;\u20090.05). Glucose levels significantly improved in LM group with a greater reduction in the area under the glucose curve during OGTT (AUCGluc<jats:sub>0_120min<\/jats:sub>) as compared to the M group (\u22124425\u2009\u00b1\u2009871 vs \u22121116\u2009\u00b1\u20091104\u00a0mg\/dl\/120\u00a0min, p\u2009&lt;\u20090.001). Pancreatic \u03b2-cell function measured with the disposition index, improved only in LM group (2.3\u2009\u00b1\u20090.23 vs 1.7\u2009\u00b1\u20090.27, p 0.001); these improvements persisted after controlling for OGTT glucose levels. The differences in pancreatic \u03b2-cell function persisted also after pairing groups for basal AUCGluc<jats:sub>0_120min<\/jats:sub>. The addition of linagliptin to patients with persistent IGT after 12\u00a0months of treatment with metformin and lifestyle, improved glucose levels during OGTT and pancreatic \u03b2-cell function after 6\u00a0months of treatment.<\/jats:p><jats:p>Trial registration: Clinicaltrials.gov with the ID number NCT04088461<\/jats:p>","DOI":"10.1038\/s41598-021-88108-8","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T10:10:11Z","timestamp":1619086211000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effect of linagliptin on glucose metabolism and pancreatic beta cell function in patients with persistent prediabetes after metformin and lifestyle"],"prefix":"10.1038","volume":"11","author":[{"given":"Mildred F\u00e1tima de la Luz","family":"Alvarez-Canales","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Stephania","family":"Salazar-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Farf\u00e1n-V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosceline Estrella","family":"Mart\u00ednez-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Noem\u00ed","family":"Gonz\u00e1lez-Mena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilia Marisela","family":"Jim\u00e9nez-Ceja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katya","family":"Vargas-Ortiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Lola","family":"Evia-Viscarra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Luisa","family":"Montes de Oca-Loyola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Folli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Aguilar-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo","family":"Guardado-Mendoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"88108_CR1","doi-asserted-by":"publisher","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","volume":"157","author":"P Saeedi","year":"2019","unstructured":"Saeedi, P. et al. 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