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

Authors
  • Shuster, Diana L1
  • Shireman, Laura M2
  • Ma, Xiaosu3
  • Shen, Danny D2
  • Flood Nichols, Shannon K4
  • Ahmed, Mahmoud S5
  • Clark, Shannon5
  • Caritis, Steve6
  • Venkataramanan, Raman6, 7
  • Haas, David M8
  • Quinney, Sara K8
  • Haneline, Laura S9
  • Tita, Alan T10
  • Manuck, Tracy A11
  • Thummel, Kenneth E2
  • Brown, Linda Morris12
  • Ren, Zhaoxia13
  • Brown, Zane14
  • Easterling, Thomas R14, 15
  • Hebert, Mary F14, 15
  • 1 Clinical Pharmacology - Scientific Affairs, PRA Health Sciences, Lenexa, Kansas, USA.
  • 2 Departments of Pharmaceutics, University of Washington, Seattle, Washington, USA.
  • 3 Global PK/PD & Pharmacometrics, Eli Lilly and Company, Indianapolis, Indiana, USA. , (India)
  • 4 Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Madigan Army Medical Center, Tacoma, Washington, USA.
  • 5 Department of Obstetrics & Gynecology, University of Texas Medical Branch in Galveston, Galveston, Texas, USA.
  • 6 Departments of Obstetrics & Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • 7 Department of Pharmacy, Pharmaceutical Sciences and Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • 8 Departments of Obstetrics & Gynecology, Indiana University, Indianapolis, Indiana, USA. , (India)
  • 9 Department of Pediatrics, Indiana University, Indianapolis, Indiana, USA. , (India)
  • 10 Department of Obstetrics & Gynecology, Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • 11 Department of Obstetrics & Gynecology, University of North Carolina, Chapel Hill, North Carolina, USA.
  • 12 RTI International, Environmental, and Health Science Unit, Biostatistics and Epidemiology Division, Rockville, Maryland, USA.
  • 13 Obstetric and Pediatric Pharmacology and Therapeutic Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
  • 14 Department of Obstetrics & Gynecology, University of Washington, Seattle, Washington, USA.
  • 15 Department of Pharmacy, University of Washington, Seattle, Washington, USA.
Type
Published Article
Journal
Clinical Pharmacology & Therapeutics
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jun 01, 2020
Volume
107
Issue
6
Pages
1362–1372
Identifiers
DOI: 10.1002/cpt.1749
PMID: 31869430
Source
Medline
Language
English
License
Unknown

Abstract

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), β-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 β-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 β-cell responsivity with GLY or supplementing with insulin might be a more optimal strategy for GDM management than monotherapy. © 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.

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