{"doi":"10.1111/dom.14767","title":"<scp>Type 2 diabetes</scp> subgroups and response to glucose‐lowering therapy: Results from the <scp>EDICT</scp> and Qatar studies","abstract":"AIM: To examine the efficacy of glucose-lowering medications in subgroups of patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Cluster analysis was performed in participants in the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) study and the Qatar study using age, body mass index (BMI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β). Participants also underwent an oral glucose tolerance test with measurement of plasma glucose, insulin and C-peptide concentrations to derive independent measures of insulin secretion and insulin sensitivity. The response to glucose-lowering therapies (change in HbA1c) was measured in each participant cluster for 3 years. RESULTS: Three distinct and comparable clusters/groups of T2DM patients were identified in both the EDICT and Qatar studies. Participants in Group 1 had the highest HbA1c and manifested severe insulin deficiency. Participants in Group 3 had comparable insulin sensitivity to those in Group 1 but better beta-cell function and better glucose control. Participants in Group 2 had the highest BMI with severe insulin resistance accompanied by marked hyperinsulinaemia, which was primarily attributable to decreased insulin clearance. Unexpectedly, participants in Group 1 had better response to combination therapy with pioglitazone plus exenatide than with insulin therapy or metformin sequentially followed by glipizide and basal insulin, while participants in Group 2 responded equally well to both therapies despite very severe insulin resistance. CONCLUSION: Distinct metabolic phenotypes characterize different T2DM clusters and differential responses to glucose-lowering therapies. Participants with severe insulin deficiency respond better to agents that preserve beta-cell function, while, surprisingly, patients with severe insulin resistance did not respond favourably to insulin sensitizers.","journal":"Diabetes Obesity and Metabolism","year":2022,"id":275252,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.799,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":351945,"name":"Curtiss Puckett","orcid":null,"position":1,"is_corresponding":false},{"id":944779,"name":"Osama Migahid","orcid":null,"position":2,"is_corresponding":false},{"id":578851,"name":"Siham Abdelgani","orcid":null,"position":3,"is_corresponding":false},{"id":944780,"name":"A. Migahed","orcid":null,"position":4,"is_corresponding":false},{"id":349925,"name":"John M. Adams","orcid":"0000-0002-6794-6904","position":5,"is_corresponding":false},{"id":349928,"name":"Curtis Triplitt","orcid":"0000-0002-7775-7816","position":6,"is_corresponding":false},{"id":383078,"name":"Ralph A. DeFronzo","orcid":"0000-0003-3839-1724","position":7,"is_corresponding":false},{"id":944376,"name":"Amin Jayyousi","orcid":"0000-0003-3174-3037","position":8,"is_corresponding":false},{"id":349924,"name":"Muhammad Abdul‐Ghani","orcid":"0000-0003-4556-1787","position":9,"is_corresponding":false},{"id":944778,"name":"Tamam Abdul‐Ghani","orcid":null,"position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T00:28:16.928746Z","pmid":"35581905","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":[]}