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

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 i...

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Main Authors: JOHN ADAMS, Ralph A DeFronzo, Aurora Merovci, Curtis Triplitt, Muhammad Abdul-Ghani, Curtiss Puckett, Siham Abdelgani, Olga Lavrynenko
Format: Article
Language:English
Published: BMJ Publishing Group 2025-04-01
Series:BMJ Open Diabetes Research & Care
Online Access:https://drc.bmj.com/content/13/2/e004981.full
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author JOHN ADAMS
Ralph A DeFronzo
Aurora Merovci
Curtis Triplitt
Muhammad Abdul-Ghani
Curtiss Puckett
Siham Abdelgani
Olga Lavrynenko
author_facet JOHN ADAMS
Ralph A DeFronzo
Aurora Merovci
Curtis Triplitt
Muhammad Abdul-Ghani
Curtiss Puckett
Siham Abdelgani
Olga Lavrynenko
author_sort JOHN ADAMS
collection DOAJ
description 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.
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spelling doaj-art-1034cef8eac94a99a1acbed2be5fcae82025-08-20T02:33:23ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972025-04-0113210.1136/bmjdrc-2025-004981Glycemic and non-glycemic benefits of initial triple therapy versus sequential add-on therapy in patients with new-onset diabetes: results from the EDICT studyJOHN ADAMS0Ralph A DeFronzo1Aurora Merovci2Curtis Triplitt3Muhammad Abdul-Ghani4Curtiss Puckett5Siham Abdelgani6Olga Lavrynenko7Diabetes Division, UT Health San Antonio, San Antonio, Texas, USADiabetes Division, UT Health San Antonio, San Antonio, Texas, USADiabetes Division, UT Health San Antonio, San Antonio, Texas, USADiabetes Division, UT Health San Antonio, San Antonio, Texas, USADiabetes Division, UT Health San Antonio, San Antonio, Texas, USADiabetes Division, UT Health San Antonio, San Antonio, Texas, USADiabetes Division, UT Health San Antonio, San Antonio, Texas, USADiabetes Division, UT Health San Antonio, San Antonio, Texas, USAIntroduction 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.https://drc.bmj.com/content/13/2/e004981.full
spellingShingle JOHN ADAMS
Ralph A DeFronzo
Aurora Merovci
Curtis Triplitt
Muhammad Abdul-Ghani
Curtiss Puckett
Siham Abdelgani
Olga Lavrynenko
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 Research & Care
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url https://drc.bmj.com/content/13/2/e004981.full
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