{"doi":"10.1210/clinem/dgab046","title":"Mifepristone Improves Adipose Tissue Insulin Sensitivity in Insulin Resistant Individuals","abstract":"BACKGROUND: Increased tissue cortisol availability has been implicated in abnormal glucose and fat metabolism in patients with obesity, metabolic syndrome, and type 2 diabetes (T2DM). Our objective was to evaluate whether blockade of glucocorticoid receptor (GR) with mifepristone ameliorates insulin resistance (IR) in overweight/obese subjects with glucose intolerance. METHODS: We conducted a randomized, double-blinded, placebo-controlled, crossover study in overweight/obese individuals (n = 16, 44% female) with prediabetes or mild T2DM but not clinical hypercortisolism. Mifepristone (50 mg every 6 h) or placebo was administered for 9 days, followed by crossover to the other treatment arm after a washout period of 6 to 8weeks. At baseline and following each treatment, oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIVGTT) were performed. Insulin sensitivity was measured using FSIVGTT [primary outcome: insulin sensitivity index (SI)] and OGTT [Matsuda index (MI) and oral glucose insulin sensitivity index (OGIS)]. Hepatic and adipose insulin resistance were assessed using hepatic insulin resistance index (HIRI), and adipose tissue insulin sensitivity index (Adipo-SI) and adipo-IR, derived from the FSIVGTT. RESULTS: Mifepristone administration did not alter whole-body glucose disposal indices of insulin sensitivity (SI, MI, and OGIS). GR blockade significantly improved Adipo-SI (61.7 ± 32.9 vs 42.8 ± 23.9; P = 0.002) and reduced adipo-IR (49.9 ± 45.9 vs 65.5 ± 43.8; P = 0.004), and HIRI (50.2 ± 38.7 vs 70.0 ± 44.3; P = 0.08). Mifepristone increased insulin clearance but did not affect insulin secretion or β-cell glucose sensitivity. CONCLUSION: Short-term mifepristone administration improves adipose and hepatic insulin sensitivity among obese individuals with hyperglycemia without hypercortisolism.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":186241,"datarank":1.0857146995993936,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.6090066250472016,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.6090066250472016,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":23,"citers_with_citation_signal":17,"citers_with_endowment":17,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.961,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01419535"]},"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":446037,"name":"Ranganath Muniyappa","orcid":"0000-0003-4198-1055","position":1,"is_corresponding":false},{"id":743600,"name":"Susmeeta T. Sharma","orcid":"0000-0002-8954-4535","position":2,"is_corresponding":false},{"id":723212,"name":"Shivraj Grewal","orcid":"0000-0002-5314-963X","position":3,"is_corresponding":false},{"id":498200,"name":"Raven McGlotten","orcid":"0000-0001-5817-9232","position":4,"is_corresponding":false},{"id":417806,"name":"Lynnette K. Nieman","orcid":"0000-0003-0534-8025","position":5,"is_corresponding":false},{"id":108961,"name":"Sriram Gubbi","orcid":"0000-0002-9263-1381","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-18T23:48:42.632147Z","pmid":"33507248","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":[]}