{"doi":"10.2337/dc24-0171","title":"Early Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials","abstract":"OBJECTIVE: Mixed-meal tolerance test-stimulated area under the curve (AUC) C-peptide at 12-24 months represents the primary end point for nearly all intervention trials seeking to preserve β-cell function in recent-onset type 1 diabetes. We hypothesized that participant benefit might be detected earlier and predict outcomes at 12 months posttherapy. Such findings would support shorter trials to establish initial efficacy. RESEARCH DESIGN AND METHODS: We examined data from six Type 1 Diabetes TrialNet immunotherapy randomized controlled trials in a post hoc analysis and included additional stimulated metabolic indices beyond C-peptide AUC. We partitioned the analysis into successful and unsuccessful trials and analyzed the data both in the aggregate as well as individually for each trial. RESULTS: Among trials meeting their primary end point, we identified a treatment effect at 3 and 6 months when using C-peptide AUC (P = 0.030 and P < 0.001, respectively) as a dynamic measure (i.e., change from baseline). Importantly, no such difference was seen in the unsuccessful trials. The use of C-peptide AUC as a 6-month dynamic measure not only detected treatment efficacy but also suggested long-term C-peptide preservation (R2 for 12-month C-peptide AUC adjusted for age and baseline value was 0.80, P < 0.001), and this finding supported the concept of smaller trial sizes down to 54 participants. CONCLUSIONS: Early dynamic measures can identify a treatment effect among successful immune therapies in type 1 diabetes trials with good long-term prediction and practical sample size over a 6-month period. While external validation of these findings is required, strong rationale and data exist in support of shortening early-phase clinical trials.","journal":"Diabetes Care","year":2024,"id":455680,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":328459,"name":"David Cuthbertson","orcid":"0000-0002-3785-9834","position":1,"is_corresponding":false},{"id":513361,"name":"Brian N. Bundy","orcid":"0000-0003-3478-714X","position":2,"is_corresponding":false},{"id":23929,"name":"Mark A. Atkinson","orcid":"0000-0001-8489-4782","position":3,"is_corresponding":false},{"id":618086,"name":"Wayne D. Moore","orcid":"0000-0003-0247-0826","position":4,"is_corresponding":false},{"id":356520,"name":"Michael J. Haller","orcid":"0000-0002-2803-1824","position":5,"is_corresponding":false},{"id":374833,"name":"William E. Russell","orcid":"0000-0001-7609-0434","position":6,"is_corresponding":false},{"id":336607,"name":"Stephen E. Gitelman","orcid":"0000-0003-4186-4107","position":7,"is_corresponding":false},{"id":230352,"name":"Kevan C. Herold","orcid":"0000-0003-1534-6613","position":8,"is_corresponding":false},{"id":7390,"name":"María J. Redondo","orcid":"0000-0001-5871-4645","position":9,"is_corresponding":false},{"id":500635,"name":"Emily K. Sims","orcid":"0000-0002-4393-954X","position":10,"is_corresponding":false},{"id":393225,"name":"Diane K. Wherrett","orcid":"0000-0003-0629-5316","position":11,"is_corresponding":false},{"id":513353,"name":"Antoinette Moran","orcid":"0000-0002-2694-5147","position":12,"is_corresponding":false},{"id":251269,"name":"Alberto Pugliese","orcid":"0000-0002-7211-0319","position":13,"is_corresponding":false},{"id":336608,"name":"Peter A. Gottlieb","orcid":"0000-0002-7601-8536","position":14,"is_corresponding":false},{"id":512512,"name":"Jay M. Sosenko","orcid":"0000-0002-7204-8367","position":15,"is_corresponding":false},{"id":577042,"name":"Heba M. Ismail","orcid":"0000-0003-0102-0030","position":16,"is_corresponding":false},{"id":71416,"name":"Type 1 Diabetes TrialNet Study Group","orcid":null,"position":17,"is_corresponding":false},{"id":506257,"name":"Laura M. Jacobsen","orcid":"0000-0002-5144-7836","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T02:03:22.974789Z","pmid":"38621411","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":[]}