Glycemic and non-glycemic benefits of initial triple therapy versus sequential add-on therapy in patients with new-onset diabetes: results from the EDICT study

BMJ Open Diabetes Res Care. 2025 Apr 27;13(2):e004981. doi: 10.1136/bmjdrc-2025-004981.

Abstract

Introduction: To compare carotid intima-media thickness (cIMT) and liver fat content in subjects who maintained good glycemic control for 6 years on initial triple therapy with metformin/exenatide/pioglitazone versus sequential add-on therapy with metformin followed with glipizide and basal insulin in subjects with new-onset diabetes.

Research design and methods: Liver fat content and cIMT were compared among patients with T2DM who received initial triple therapy with metformin/pioglitazone/exenatide (n=29) versus metformin, followed by stepwise addition of glipizide and then insulin glargine (n=26) and who maintained HbA1c<6.5% for 6 years in Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes.

Results: After 6 years in subjects receiving initial triple therapy with metformin/pioglitazone/exenatide and subjects receiving sequential addition of metformin followed by glipizide and insulin glargine had a mean HbA1c of 5.7% vs 6.0%, respectively, p=NS. Nonetheless, subjects receiving sequential add-on therapy experienced a greater increase in cIMT and manifested greater liver fat content and fibrosis than subjects receiving initial triple therapy.

Conclusions: Including pioglitazone plus exenatide in the glucose-lowering regimen slows the progression of cIMT and was associated with lower hepatic fat content and fibrosis compared with subjects receiving sequential add-on therapy without pioglitazone and exenatide despite comparable optimal glycemic control.

Trial registration number: NCT01107717.

Keywords: Diabetes Mellitus, Type 2; Disease Management; Glucagon-Like Peptide 1; Thiazolidinediones.

Publication types

  • Clinical Trial, Phase IV
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers / analysis
  • Blood Glucose / analysis
  • Carotid Intima-Media Thickness
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / pathology
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Glipizide / administration & dosage
  • Glipizide / therapeutic use
  • Glycated Hemoglobin / analysis
  • Glycemic Control
  • Humans
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / therapeutic use
  • Insulin Glargine / administration & dosage
  • Insulin Glargine / therapeutic use
  • Male
  • Metformin / administration & dosage
  • Metformin / therapeutic use
  • Middle Aged
  • Pioglitazone

Substances

  • Biomarkers
  • Blood Glucose
  • Glipizide
  • Glycated Hemoglobin
  • hemoglobin A1c protein, human
  • Hypoglycemic Agents
  • Insulin Glargine
  • Metformin
  • Pioglitazone

Associated data

  • ClinicalTrials.gov/NCT01107717