{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T20:56:30Z","timestamp":1776113790155,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To examine the efficacy of glucose\u2010lowering medications in subgroups of patients with type 2 diabetes mellitus (T2DM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research design and methods<\/jats:title>\n                    <jats:p>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\u2010IR) and beta\u2010cell function (HOMA\u2010\u03b2). Participants also underwent an oral glucose tolerance test with measurement of plasma glucose, insulin and C\u2010peptide concentrations to derive independent measures of insulin secretion and insulin sensitivity. The response to glucose\u2010lowering therapies (change in HbA1c) was measured in each participant cluster for 3\u2009years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2010cell 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Distinct metabolic phenotypes characterize different T2DM clusters and differential responses to glucose\u2010lowering therapies. Participants with severe insulin deficiency respond better to agents that preserve beta\u2010cell function, while, surprisingly, patients with severe insulin resistance did not respond favourably to insulin sensitizers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14767","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T01:14:22Z","timestamp":1652836462000},"page":"1810-1818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>Type 2 diabetes<\/scp>\n                    subgroups and response to glucose\u2010lowering therapy: Results from the\n                    <scp>EDICT<\/scp>\n                    and Qatar studies"],"prefix":"10.1111","volume":"24","author":[{"given":"Tamam","family":"Abdul\u2010Ghani","sequence":"first","affiliation":[{"name":"Division of Diabetes University of Texas Health Science Center and Texas Diabetes Institute  San Antonio Texas 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