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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 E fficacy and D urability of I nitial C ombination T herapy for T ype 2 D iabetes ( EDICT ): a randomized trial

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Abdul‐Ghani, M. A., Puckett, C., Triplitt, C., Maggs, D., Adams, J., Cersosimo, E., DeFronzo, R. A·2015·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.12417PMC PMC5577982
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Abstract

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‐naïve, 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.

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Authors
Abdul‐Ghani, M. A., Puckett, C., Triplitt, C., Maggs, D., Adams, J., Cersosimo, E., & DeFronzo, R. A.
Affiliations
  • The University of Texas at San Antonio Health Science Center (US)
  • GI Dynamics (United States) (US)
  • Diabetes Division University of Texas Health Science Center at San Antonio San Antonio TX USA
Corresponding author
DeFronzo, R. A
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2015-01-07
Volume
17
Issue
3
Pages
268-275
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.12417
PMC
PMC5577982
OpenAlex
W2060716197
Cited by
208
References
9
Citations by year
2026: 14 · 2025: 12 · 2024: 20 · 2023: 15 · 2022: 19 · 2021: 15 · 2020: 23 · 2019: 15 · 2018: 22 · 2017: 29 · 2016: 18 · 2015: 6
FWCI
14.20
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Diabetes Obesity and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • The American Diabetes Association Research Foundation
  • Amylin Pharmaceuticals
  • Bristol-Myers Squibb
  • AstraZeneca
  • Eli Lilly and Company
  • Takeda Pharmaceuticals North America
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
type 2 diabetes, new-onset diabetes, combination therapy, metformin, pioglitazone, exenatide, sulfonylureas, insulin glargine, HbA1c, hypoglycemia, weight gain, insulin secretion, insulin sensitivity
MeSH terms
Pioglitazone, Exenatide, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin Resistance, Male, Metformin, Middle Aged, Peptides, Venoms, Weight Gain, Weight Loss, Thiazolidinediones

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