{"doi":"10.1210/clinem/dgab170","title":"Two-Year Treatment With Metformin During Puberty Does Not Preserve β-Cell Function in Youth With Obesity","abstract":"CONTEXT: Youth-onset type 2 diabetes is a disease of pubertal onset, associated with additional burden of pubertal insulin resistance on the β-cell. OBJECTIVE: Evaluate the impact of metformin treatment during puberty, a critical window of cardiometabolic change, on insulin sensitivity (Si) and compensatory β-cell response in youth with obesity. SETTING: Pediatric academic hospital clinical translational research center. PARTICIPANTS: Healthy youth in early puberty [Tanner stage (T) 2-3] with normoglycemia and obesity (n = 44). INTERVENTION: Double-blinded placebo-control trial of metformin during puberty (until T5). MAIN OUTCOME MEASURES: Insulin sensitivity (Si), insulin response [acute insulin response to glucose (AIRg)], and disposition index (DI), estimated from frequently sampled intravenous glucose tolerance testing; body fat (dual X-ray absorptiometry); and other laboratory parameters, collected at baseline, T4, and T5. Placebo-subtracted treatment effect was calculated using linear mixed models. RESULTS: At T5, metformin treatment, adjusting for sex, race, and baseline value, was associated with improved BMI z-score (-0.44 ± 0.16, P = 0.02), percentage body fat (%body fat; -3.4 ± 1.2%, P = 0.06), and waist circumference (-11.3 ± 3.2cm, P = 0.003). There were no significant treatment effects at T5 on Si or secretion: Si (0.85 ± 0.87 × 10-4/min-1/μIU/mL, P = 0.34), AIRg (-259 ± 386 μIU/mL, P = 0.51), or DI (508 ± 802 × 10-4/min-1, P = 0.53). High baseline DI predicted longitudinal decline in DI. CONCLUSIONS: Two years of metformin treatment in obese youth during puberty improved BMI and body fat, but not Si or β-cell function. Of note, high DI in early puberty may be predictive of later decline in DI. Further studies are needed to develop strategies for preservation of β-cell function in youth at risk for type 2 diabetes.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":179285,"datarank":0.624384573882401,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.1827187270074349,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.1827187270074349,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":14,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01775813"]},"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":335756,"name":"Allison Hilkin","orcid":null,"position":1,"is_corresponding":false},{"id":254435,"name":"Laura Pyle","orcid":"0000-0001-5577-8221","position":2,"is_corresponding":false},{"id":334623,"name":"Cameron Severn","orcid":"0000-0001-9562-581X","position":3,"is_corresponding":false},{"id":249040,"name":"Kristina M. Utzschneider","orcid":"0000-0002-4924-196X","position":4,"is_corresponding":false},{"id":334624,"name":"Rachael E. Van Pelt","orcid":"0000-0003-4187-7063","position":5,"is_corresponding":false},{"id":334625,"name":"Philip Zeitler","orcid":"0000-0001-5756-7858","position":6,"is_corresponding":false},{"id":7391,"name":"Kristen J. Nadeau","orcid":"0000-0002-0477-3356","position":7,"is_corresponding":false},{"id":254437,"name":"Megan M. Kelsey","orcid":"0000-0002-0755-1951","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T23:47:44.875897Z","pmid":"33728428","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":[]}