Type 2 diabetes subgroups and response to glucose-lowering therapy: Results from the EDICT and Qatar studies

Tamam Abdul-Ghani, Curtiss Puckett, Osama Migahid, Siham Abdelgani, Ayman Migahed, John Adams, Curtis Triplitt, Ralph DeFronzo, Amin Jayyousi, Muhammad Abdul-Ghani

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1810-1818
Number of pages9
JournalDiabetes, Obesity and Metabolism
Volume24
Issue number9
DOIs
StatePublished - Sep 2022

Keywords

  • cluster analysis
  • glucose-lowering therapy
  • type 2 diabetes subgroups

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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