PMID- 31869430
OWN - NLM
STAT- MEDLINE
DCOM- 20210216
LR  - 20220323
IS  - 1532-6535 (Electronic)
IS  - 0009-9236 (Print)
IS  - 0009-9236 (Linking)
VI  - 107
IP  - 6
DP  - 2020 Jun
TI  - Pharmacodynamics of Glyburide, Metformin, and Glyburide/Metformin Combination 
      Therapy in the Treatment of Gestational Diabetes Mellitus.
PG  - 1362-1372
LID - 10.1002/cpt.1749 [doi]
AB  - 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.
CI  - (c) 2019 The Authors Clinical Pharmacology & Therapeutics (c) 2019 American Society 
      for Clinical Pharmacology and Therapeutics.
FAU - Shuster, Diana L
AU  - Shuster DL
AD  - Clinical Pharmacology - Scientific Affairs, PRA Health Sciences, Lenexa, Kansas, 
      USA.
FAU - Shireman, Laura M
AU  - Shireman LM
AD  - Departments of Pharmaceutics, University of Washington, Seattle, Washington, USA.
FAU - Ma, Xiaosu
AU  - Ma X
AD  - Global PK/PD & Pharmacometrics, Eli Lilly and Company, Indianapolis, Indiana, 
      USA.
FAU - Shen, Danny D
AU  - Shen DD
AD  - Departments of Pharmaceutics, University of Washington, Seattle, Washington, USA.
FAU - Flood Nichols, Shannon K
AU  - Flood Nichols SK
AD  - Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, 
      Madigan Army Medical Center, Tacoma, Washington, USA.
FAU - Ahmed, Mahmoud S
AU  - Ahmed MS
AD  - Department of Obstetrics & Gynecology, University of Texas Medical Branch in 
      Galveston, Galveston, Texas, USA.
FAU - Clark, Shannon
AU  - Clark S
AD  - Department of Obstetrics & Gynecology, University of Texas Medical Branch in 
      Galveston, Galveston, Texas, USA.
FAU - Caritis, Steve
AU  - Caritis S
AUID- ORCID: 0000-0002-2169-0712
AD  - Departments of Obstetrics & Gynecology, University of Pittsburgh, Pittsburgh, 
      Pennsylvania, USA.
FAU - Venkataramanan, Raman
AU  - Venkataramanan R
AD  - Departments of Obstetrics & Gynecology, University of Pittsburgh, Pittsburgh, 
      Pennsylvania, USA.
AD  - Department of Pharmacy, Pharmaceutical Sciences and Pathology, University of 
      Pittsburgh, Pittsburgh, Pennsylvania, USA.
FAU - Haas, David M
AU  - Haas DM
AD  - Departments of Obstetrics & Gynecology, Indiana University, Indianapolis, 
      Indiana, USA.
FAU - Quinney, Sara K
AU  - Quinney SK
AUID- ORCID: 0000-0002-6554-0695
AD  - Departments of Obstetrics & Gynecology, Indiana University, Indianapolis, 
      Indiana, USA.
FAU - Haneline, Laura S
AU  - Haneline LS
AD  - Department of Pediatrics, Indiana University, Indianapolis, Indiana, USA.
FAU - Tita, Alan T
AU  - Tita AT
AD  - Department of Obstetrics & Gynecology, Center for Women's Reproductive Health, 
      University of Alabama at Birmingham, Birmingham, Alabama, USA.
FAU - Manuck, Tracy A
AU  - Manuck TA
AD  - Department of Obstetrics & Gynecology, University of North Carolina, Chapel Hill, 
      North Carolina, USA.
FAU - Thummel, Kenneth E
AU  - Thummel KE
AD  - Departments of Pharmaceutics, University of Washington, Seattle, Washington, USA.
FAU - Brown, Linda Morris
AU  - Brown LM
AD  - RTI International, Environmental, and Health Science Unit, Biostatistics and 
      Epidemiology Division, Rockville, Maryland, USA.
FAU - Ren, Zhaoxia
AU  - Ren Z
AD  - Obstetric and Pediatric Pharmacology and Therapeutic Branch, Eunice Kennedy 
      Shriver National Institute of Child Health and Human Development, Bethesda, 
      Maryland, USA.
FAU - Brown, Zane
AU  - Brown Z
AD  - Department of Obstetrics & Gynecology, University of Washington, Seattle, 
      Washington, USA.
FAU - Easterling, Thomas R
AU  - Easterling TR
AD  - Department of Obstetrics & Gynecology, University of Washington, Seattle, 
      Washington, USA.
AD  - Department of Pharmacy, University of Washington, Seattle, Washington, USA.
FAU - Hebert, Mary F
AU  - Hebert MF
AD  - Department of Obstetrics & Gynecology, University of Washington, Seattle, 
      Washington, USA.
AD  - Department of Pharmacy, University of Washington, Seattle, Washington, USA.
LA  - eng
GR  - U10 HD063094/HD/NICHD NIH HHS/United States
GR  - U10 HD047905/HD/NICHD NIH HHS/United States
GR  - U10 HD057753/HD/NICHD NIH HHS/United States
GR  - UL1 TR001108/TR/NCATS NIH HHS/United States
GR  - TL1 TR000422/TR/NCATS NIH HHS/United States
GR  - U10 HD047891/HD/NICHD NIH HHS/United States
GR  - R01 GM124264/GM/NIGMS NIH HHS/United States
GR  - U54 HD047905/HD/NICHD NIH HHS/United States
GR  - UL1 TR000423/TR/NCATS NIH HHS/United States
GR  - U10 HD047892/HD/NICHD NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200125
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Blood Glucose)
RN  - 0 (Hypoglycemic Agents)
RN  - 9100L32L2N (Metformin)
RN  - SX6K58TVWC (Glyburide)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Blood Glucose/drug effects
MH  - Diabetes, Gestational/*drug therapy
MH  - Drug Therapy, Combination
MH  - Female
MH  - Glyburide/*administration & dosage/pharmacology
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage/pharmacology
MH  - Insulin Resistance
MH  - Insulin-Secreting Cells/metabolism
MH  - Longitudinal Studies
MH  - Metformin/*administration & dosage/pharmacology
MH  - Pregnancy
MH  - Prospective Studies
MH  - Young Adult
PMC - PMC7561209
MID - NIHMS1634110
COIS- Conflict of Interest/Disclosure The authors declare that at the time of the 
      conduct and analysis of the study, they had no competing interests for this work. 
      However, since the completion of the study, D.L.S.'s affiliation has changed to 
      PRAHealthSciences.
EDAT- 2019/12/24 06:00
MHDA- 2021/02/17 06:00
PMCR- 2021/06/01
CRDT- 2019/12/24 06:00
PHST- 2019/06/20 00:00 [received]
PHST- 2019/10/23 00:00 [accepted]
PHST- 2019/12/24 06:00 [pubmed]
PHST- 2021/02/17 06:00 [medline]
PHST- 2019/12/24 06:00 [entrez]
PHST- 2021/06/01 00:00 [pmc-release]
AID - 10.1002/cpt.1749 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 2020 Jun;107(6):1362-1372. doi: 10.1002/cpt.1749. Epub 2020 
      Jan 25.