{"doi":"10.1210/clinem/dgab365","title":"Effect of Sitagliptin on Islet Function in Pancreatic Insufficient Cystic Fibrosis With Abnormal Glucose Tolerance","abstract":"PURPOSE: Impaired incretin secretion may contribute to the defective insulin secretion and abnormal glucose tolerance (AGT) that associate with worse clinical outcomes in pancreatic insufficient cystic fibrosis (PI-CF). The study objective was to test the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitor-induced increases in intact incretin hormone [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] concentrations augment insulin secretion and glucagon suppression and lower postprandial glycemia in PI-CF with AGT. METHODS: 26 adults from Children's Hospital of Philadelphia and University of Pennsylvania CF Center with PI-CF and AGT [defined by oral glucose tolerance test glucose (mg/dL): early glucose intolerance (1-h ≥ 155 and 2-h < 140), impaired glucose tolerance (2-h ≥ 140 and < 200 mg/dL), or diabetes (2-h ≥ 200)] were randomized to a 6-month double-blind trial of DPP-4 inhibitor sitagliptin 100 mg daily or matched placebo; 24 completed the trial (n = 12 sitagliptin; n = 12 placebo). Main outcome measures were mixed-meal tolerance test (MMTT) responses for intact GLP-1 and GIP, insulin secretory rates (ISRs), glucagon suppression, and glycemia and glucose-potentiated arginine (GPA) test-derived measures of β- and α-cell function. RESULTS: Following 6-months of sitagliptin vs placebo, MMTT intact GLP-1 and GIP responses increased (P < 0.001), ISR dynamics improved (P < 0.05), and glucagon suppression was modestly enhanced (P < 0.05) while GPA test responses for glucagon were lower. No improvements in glucose tolerance or β-cell sensitivity to glucose, including for second-phase insulin response, were found. CONCLUSIONS: In glucose intolerant PI-CF, sitagliptin intervention augmented meal-related incretin responses with improved early insulin secretion and glucagon suppression without affecting postprandial glycemia.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":159983,"datarank":1.1287573101660175,"base_score":3.6635616461296463,"endowment":3.6635616461296463,"self_citation_contribution":0.5495342469194471,"citation_network_contribution":0.5792230632465705,"self_endowment_contribution":0.5495342469194471,"citer_contribution":0.5792230632465705,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":26,"citers_with_citation_signal":19,"citers_with_endowment":19,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01879228"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":500489,"name":"Saba Sheikh","orcid":"0000-0002-4164-6663","position":1,"is_corresponding":false},{"id":341656,"name":"Darko Stefanovski","orcid":"0000-0002-4654-0569","position":2,"is_corresponding":false},{"id":672101,"name":"Amy J. Peleckis","orcid":"0000-0002-3772-2782","position":3,"is_corresponding":false},{"id":672102,"name":"Sarah C. Nyirjesy","orcid":"0000-0001-7304-7211","position":4,"is_corresponding":false},{"id":673036,"name":"Jack N. Eiel","orcid":null,"position":5,"is_corresponding":false},{"id":672103,"name":"Aniket Sidhaye","orcid":"0000-0001-9493-4776","position":6,"is_corresponding":false},{"id":472288,"name":"Russell Localio","orcid":null,"position":7,"is_corresponding":false},{"id":331682,"name":"Robert Gallop","orcid":"0000-0001-9986-2994","position":8,"is_corresponding":false},{"id":542261,"name":"Diva D. De León","orcid":"0000-0003-1225-8087","position":9,"is_corresponding":false},{"id":500491,"name":"Denis Hadjiliadis","orcid":"0000-0002-8602-9503","position":10,"is_corresponding":false},{"id":383735,"name":"Ronald C. Rubenstein","orcid":"0000-0002-3138-4006","position":11,"is_corresponding":false},{"id":231672,"name":"Michael R. Rickels","orcid":"0000-0002-9253-838X","position":12,"is_corresponding":false},{"id":32955,"name":"Andrea Kelly","orcid":"0000-0003-1724-9868","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:44:43.908634Z","pmid":"34406395","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}