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Pharmacodynamics of Metformin in Pregnant Women With Gestational Diabetes Mellitus and Nonpregnant Women With Type 2 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, Raman7
  • Haas, David M8
  • Quinney, Sara K8
  • Haneline, Laura S8
  • Tita, Alan T9
  • Manuck, Tracy A10
  • Thummel, Kenneth E2
  • Morris Brown, Linda11
  • Ren, Zhaoxia12
  • Brown, Zane2
  • Easterling, Thomas R2
  • Hebert, Mary F2
  • 1 PRA Health Sciences, Clinical Pharmacology-Scientific Affairs, Lenexa, Kansas, USA.
  • 2 University of Washington, Departments of Pharmaceutics, Obstetrics & Gynecology, and Pharmacy, Seattle, Washington, USA.
  • 3 Global PK/PD & Pharmacometrics, Eli Lilly and Company, Indianapolis, Indiana, USA. , (India)
  • 4 Madigan Army Medical Center, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Tacoma, Washington, USA.
  • 5 University of Texas Medical Branch in Galveston, Department of Obstetrics & Gynecology, Galveston, Texas, USA.
  • 6 University of Pittsburgh, Department of Obstetrics & Gynecology, Pittsburgh, Pennsylvania, USA.
  • 7 University of Pittsburgh, Departments of Pharmacy, Pharmaceutical Sciences and Pathology, Pittsburgh, Pennsylvania, USA.
  • 8 Indiana University, Departments of Obstetrics & Gynecology and Pediatrics, Indianapolis, Indiana, USA. , (India)
  • 9 University of Alabama at Birmingham, Department of Obstetrics & Gynecology, Birmingham, Alabama, USA.
  • 10 University of North Carolina, Department of Obstetrics & Gynecology, Chapel Hill, North Carolina, USA.
  • 11 RTI International, Environmental and Health Science Unit, Biostatistics and Epidemiology Division, Rockville, Maryland, USA.
  • 12 Obstetric and Pediatric Pharmacology and Therapeutic Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Type
Published Article
Journal
Journal of clinical pharmacology
Publication Date
Apr 01, 2020
Volume
60
Issue
4
Pages
540–549
Identifiers
DOI: 10.1002/jcph.1549
PMID: 31742716
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Gestational diabetes mellitus is a condition similar to type 2 diabetes mellitus (T2DM) in that patients are unable to compensate for the degree of insulin resistance, and both conditions are often treated with metformin. The comparative pharmacodynamic response to metformin in these 2 populations has not been studied. This study characterized insulin sensitivity, β-cell responsivity, and disposition index following a mixed-meal tolerance test utilizing a minimal model of glucose, insulin, and C-peptide kinetics before and during treatment with metformin. The study included women with gestational diabetes mellitus (n = 34), T2DM (n = 14), and healthy pregnant women (n = 30). Before treatment, the gestational diabetes mellitus group had significantly higher baseline (45%), dynamic (68%), static (71%), and total β-cell responsivity (71%) than the T2DM group. Metformin significantly increased insulin sensitivity (51%) as well as disposition index (97%) and decreased mixed-meal tolerance test peak glucose concentrations (8%) in women with gestational diabetes mellitus after adjustment for gestational age-dependent effects; however, in women with T2DM metformin only significantly affected peak glucose concentrations (22%) and had no significant effect on any other parameters. Metformin had a greater effect on the change in disposition index (Δ disposition index) in women with gestational diabetes mellitus than in those with T2DM (P = .01). In conclusion, response to metformin in women with gestational diabetes mellitus is significantly different from that in women with T2DM, which is likely related to the differences in disease severity. © 2019, The American College of Clinical Pharmacology.

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