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- Title
Durability of Triple Combination Therapy Versus Stepwise Addition Therapy in Patients With New-Onset T2DM: 3-Year Follow-up of EDICT.
- Authors
Abdul-Ghani, Muhammad; Puckett, Curtiss; Adams, John; Khattab, Ahmad; Baskoy, Gozde; Cersosimo, Eugenio; Triplitt, Curtis; DeFronzo, Ralph A.
- Abstract
<bold>Objective: </bold>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.<bold>Research Design and Methods: </bold>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 HbA1c at <6.5% (48 mmol/mol). Insulin sensitivity and β-cell function were measured at baseline and 3 years. The primary outcome was the difference in HbA1c between the groups at 3 years.<bold>Results: </bold>Baseline HbA1c ± SEM values were 9.0% ± 0.2% and 8.9% ± 0.2% in the triple therapy and conventional therapy groups, respectively. The decrease in HbA1c 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 HbA1c 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 HbA1c 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 β-cell function. In conventional therapy, insulin sensitivity did not change and β-cell function increased by only 34% (both P < 0.0001 vs. triple therapy).<bold>Conclusions: </bold>Triple therapy with agents that improve insulin sensitivity and β-cell function in patients with new-onset T2DM produces greater, more durable HbA1c reduction than agents that lower glucose levels without correcting the underlying metabolic defects.
- Subjects
TYPE 2 diabetes; INSULIN sensitivity; GLYCOSYLATED hemoglobin
- Publication
Diabetes Care, 2021, Vol 44, Issue 2, p433
- ISSN
0149-5992
- Publication type
journal article
- DOI
10.2337/dc20-0978