4.6 Article

Pharmacodynamics of Glyburide, Metformin, and Glyburide/Metformin Combination Therapy in the Treatment of Gestational Diabetes Mellitus

期刊

CLINICAL PHARMACOLOGY & THERAPEUTICS
卷 107, 期 6, 页码 1362-1372

出版社

WILEY
DOI: 10.1002/cpt.1749

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资金

  1. Eunice Kennedy Shriver National Institute of Child Health and Human Development [U10HD063094, U10HD047892, U10HD097905, U10HD047891, U10HD057753]
  2. National Institutes of Health (NIH) National Center for Advancing Translational Science through the Clinical and Translational Science Awards Program [ULITR000423, TLITR000422, ULITR001108]
  3. National Institute of General Medical Sciences [R01GM124264]
  4. University of Washington

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In gestational diabetes mellitus (GDM), women are unable to compensate for the increased insulin resistance during pregnancy. Data are limited regarding the pharmacodynamic effects of metformin and glyburide during pregnancy. This study characterized insulin sensitivity (SI), beta-cell responsivity, and disposition index (DI) in women with GDM utilizing a mixed-meal tolerance test (MMTT) before and during treatment with glyburide monotherapy (GLY, n = 38), metformin monotherapy (MET, n = 34), or GLY and MET combination therapy (COMBO; n = 36). GLY significantly decreased dynamic beta-cell responsivity (31%). MET and COMBO significantly increased SI (121% and 83%, respectively). Whereas GLY, MET, and COMBO improved DI, metformin (MET and COMBO) demonstrated a larger increase in DI (P = 0.05) and a larger decrease in MMTT peak glucose concentrations (P = 0.03) than subjects taking only GLY. Maximizing SI with MET followed by increasing beta-cell responsivity with GLY or supplementing with insulin might be a more optimal strategy for GDM management than monotherapy.

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