PMID- 25425451
OWN - NLM
STAT- MEDLINE
DCOM- 20150924
LR  - 20221207
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Print)
IS  - 1462-8902 (Linking)
VI  - 17
IP  - 3
DP  - 2015 Mar
TI  - Initial combination therapy with metformin, pioglitazone and exenatide is more 
      effective than sequential add-on therapy in subjects with new-onset diabetes. 
      Results from the Efficacy and Durability of Initial Combination Therapy for Type 
      2 Diabetes (EDICT): a randomized trial.
PG  - 268-75
LID - 10.1111/dom.12417 [doi]
AB  - AIM: To test our hypothesis that initiating therapy with a combination of agents 
      known to improve insulin secretion and insulin sensitivity in subjects with 
      new-onset diabetes would produce greater, more durable reduction in glycated 
      haemoglobin (HbA1c) levels, while avoiding hypoglycaemia and weight gain, 
      compared with sequential addition of agents that lower plasma glucose but do not 
      correct established pathophysiological abnormalities. METHODS: Drug-naive, 
      recently diagnosed subjects with type 2 diabetes mellitus (T2DM) were randomized 
      in an open-fashion design in a single-centre study to 
      metformin/pioglitazone/exenatide (triple therapy; n = 106) or an escalating dose 
      of metformin followed by sequential addition of sulfonylurea and glargine insulin 
      (conventional therapy; n = 115) to maintain HbA1c levels at <6.5% for 2 years. 
      RESULTS: Participants receiving triple therapy experienced a significantly 
      greater reduction in HbA1c level than those receiving conventional therapy (5.95 
      vs. 6.50%; p < 0.001). Despite lower HbA1c values, participants receiving triple 
      therapy experienced a 7.5-fold lower rate of hypoglycaemia compared with 
      participants receiving conventional therapy. Participants receiving triple 
      therapy experienced a mean weight loss of 1.2 kg versus a mean weight gain of 
      4.1 kg (p < 0.01) in those receiving conventional therapy. CONCLUSION: The 
      results of this exploratory study show that combination therapy with 
      metformin/pioglitazone/exenatide in patients with newly diagnosed T2DM is more 
      effective and results in fewer hypoglycaemic events than sequential add-on 
      therapy with metformin, sulfonylurea and then basal insulin.
CI  - (c) 2014 John Wiley & Sons Ltd.
FAU - Abdul-Ghani, M A
AU  - Abdul-Ghani MA
AD  - Diabetes Division, University of Texas Health Science Center at San Antonio, San 
      Antonio, TX, USA.
FAU - Puckett, C
AU  - Puckett C
FAU - Triplitt, C
AU  - Triplitt C
FAU - Maggs, D
AU  - Maggs D
FAU - Adams, J
AU  - Adams J
FAU - Cersosimo, E
AU  - Cersosimo E
FAU - DeFronzo, R A
AU  - DeFronzo RA
LA  - eng
GR  - R01 DK103841/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150107
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Peptides)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Venoms)
RN  - 0 (hemoglobin A1c protein, human)
RN  - 9100L32L2N (Metformin)
RN  - 9P1872D4OL (Exenatide)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Diabetes Mellitus, Type 2/complications/*drug therapy
MH  - Drug Therapy, Combination/methods
MH  - Exenatide
MH  - Female
MH  - Glycated Hemoglobin/drug effects
MH  - Humans
MH  - Hypoglycemia/chemically induced/etiology
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Insulin Resistance
MH  - Male
MH  - Metformin/*therapeutic use
MH  - Middle Aged
MH  - Peptides/*therapeutic use
MH  - Pioglitazone
MH  - Thiazolidinediones/*therapeutic use
MH  - Venoms/*therapeutic use
MH  - Weight Gain/drug effects
MH  - Weight Loss/drug effects
PMC - PMC5577982
MID - NIHMS898403
OTO - NOTNLM
OT  - combination therapy
OT  - conventional therapy
OT  - durability
OT  - glycaemic control
EDAT- 2014/11/27 06:00
MHDA- 2015/09/25 06:00
PMCR- 2017/08/31
CRDT- 2014/11/27 06:00
PHST- 2014/09/30 00:00 [received]
PHST- 2014/11/20 00:00 [revised]
PHST- 2014/11/20 00:00 [accepted]
PHST- 2014/11/27 06:00 [entrez]
PHST- 2014/11/27 06:00 [pubmed]
PHST- 2015/09/25 06:00 [medline]
PHST- 2017/08/31 00:00 [pmc-release]
AID - 10.1111/dom.12417 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2015 Mar;17(3):268-75. doi: 10.1111/dom.12417. Epub 2015 Jan 
      7.