PMID- 33273042
OWN - NLM
STAT- MEDLINE
DCOM- 20210820
LR  - 20221207
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 44
IP  - 2
DP  - 2021 Feb
TI  - Durability of Triple Combination Therapy Versus Stepwise Addition Therapy in 
      Patients With New-Onset T2DM: 3-Year Follow-up of EDICT.
PG  - 433-439
LID - 10.2337/dc20-0978 [doi]
AB  - OBJECTIVE: To compare the long-term efficacy of initiating therapy with 
      metformin/pioglitazone/exenatide in patients with new-onset type 2 diabetes 
      mellitus (T2DM) versus sequential addition of metformin followed by glipizide and 
      insulin. RESEARCH DESIGN AND METHODS: Drug-naive patients (N = 318) with 
      new-onset T2DM were randomly assigned to receive for 3 years either 1) 
      combination therapy with metformin, pioglitazone, and exenatide (triple therapy) 
      or 2) sequential addition of metformin followed by glipizide and insulin 
      (conventional therapy) to maintain HbA(1c) at <6.5% (48 mmol/mol). Insulin 
      sensitivity and beta-cell function were measured at baseline and 3 years. The 
      primary outcome was the difference in HbA(1c) between the groups at 3 years. 
      RESULTS: Baseline HbA(1c) +/- SEM values were 9.0% +/- 0.2% and 8.9% +/- 0.2% in the 
      triple therapy and conventional therapy groups, respectively. The decrease in 
      HbA(1c) resulting from triple therapy was greater at 6 months than that produced 
      by conventional therapy (0.30% [95% CI 0.21-0.39]; P = 0.001), and the HbA(1c) 
      reduction was maintained at 3 years in patients receiving triple therapy compared 
      with conventional therapy (6.4% +/- 0.1% and 6.9% +/- 0.1%, respectively), despite 
      intensification of antihyperglycemic therapy in the latter. Thus, the difference 
      in HbA(1c) between the two treatment groups at 3 years was 0.50% (95% CI 
      0.39-0.61; P < 0.0001). Triple therapy produced a threefold increase in insulin 
      sensitivity and 30-fold increase in beta-cell function. In conventional therapy, 
      insulin sensitivity did not change and beta-cell function increased by only 34% 
      (both P < 0.0001 vs. triple therapy). CONCLUSIONS: Triple therapy with agents 
      that improve insulin sensitivity and beta-cell function in patients with new-onset 
      T2DM produces greater, more durable HbA(1c) reduction than agents that lower 
      glucose levels without correcting the underlying metabolic defects.
CI  - (c) 2020 by the American Diabetes Association.
FAU - Abdul-Ghani, Muhammad
AU  - Abdul-Ghani M
AUID- ORCID: 0000-0003-4556-1787
AD  - Division of Diabetes, University of Texas Health Science Center and Texas 
      Diabetes Institute, San Antonio, TX.
FAU - Puckett, Curtiss
AU  - Puckett C
AD  - Division of Diabetes, University of Texas Health Science Center and Texas 
      Diabetes Institute, San Antonio, TX.
FAU - Adams, John
AU  - Adams J
AD  - Division of Diabetes, University of Texas Health Science Center and Texas 
      Diabetes Institute, San Antonio, TX.
FAU - Khattab, Ahmad
AU  - Khattab A
AD  - Division of Diabetes, University of Texas Health Science Center and Texas 
      Diabetes Institute, San Antonio, TX.
FAU - Baskoy, Gozde
AU  - Baskoy G
AD  - Division of Diabetes, University of Texas Health Science Center and Texas 
      Diabetes Institute, San Antonio, TX.
FAU - Cersosimo, Eugenio
AU  - Cersosimo E
AUID- ORCID: 0000-0002-2573-0208
AD  - Division of Diabetes, University of Texas Health Science Center and Texas 
      Diabetes Institute, San Antonio, TX.
FAU - Triplitt, Curtis
AU  - Triplitt C
AD  - Division of Diabetes, University of Texas Health Science Center and Texas 
      Diabetes Institute, San Antonio, TX.
FAU - DeFronzo, Ralph A
AU  - DeFronzo RA
AUID- ORCID: 0000-0002-8581-6273
AD  - Division of Diabetes, University of Texas Health Science Center and Texas 
      Diabetes Institute, San Antonio, TX defronzo@uthscsa.edu.
LA  - eng
SI  - figshare/10.2337/figshare.13148381
SI  - ClinicalTrials.gov/NCT01107717
GR  - R01 DK024092/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20201203
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Blood Glucose
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Drug Therapy, Combination
MH  - Follow-Up Studies
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Hypoglycemic Agents/therapeutic use
MH  - *Metformin/therapeutic use
MH  - Treatment Outcome
PMC - PMC7818318
EDAT- 2020/12/05 06:00
MHDA- 2021/08/21 06:00
PMCR- 2022/02/01
CRDT- 2020/12/04 05:37
PHST- 2020/04/28 00:00 [received]
PHST- 2020/10/17 00:00 [accepted]
PHST- 2020/12/05 06:00 [pubmed]
PHST- 2021/08/21 06:00 [medline]
PHST- 2020/12/04 05:37 [entrez]
PHST- 2022/02/01 00:00 [pmc-release]
AID - dc20-0978 [pii]
AID - 200978 [pii]
AID - 10.2337/dc20-0978 [doi]
PST - ppublish
SO  - Diabetes Care. 2021 Feb;44(2):433-439. doi: 10.2337/dc20-0978. Epub 2020 Dec 3.