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Are We Optimizing Gestational Diabetes Treatment With Glyburide? The Pharmacologic Basis for Better Clinical Practice
Open accessAbstract
Glyburide's pharmacokinetics (PK) and pharmacodynamics have not been studied in women with gestational diabetes mellitus (GDM). The objective of this study was to assess steady-state PK of glyburide, as well as insulin sensitivity, beta-cell responsivity, and overall disposition indices after a mixed-meal tolerance test (MMTT) in women with GDM (n = 40), nonpregnant women with type 2 diabetes mellitus (T2DM) (n = 26), and healthy pregnant women (n = 40, MMTT only). At equivalent doses, glyburide plasma concentrations were approximately 50% lower in pregnant women than in nonpregnant subjects. The average umbilical cord/maternal plasma glyburide concentration ratio at the time of delivery was 0.7 +/- 0.4. Insulin sensitivity was approximately fivefold lower in women with GDM as compared with healthy pregnant women. Despite comparable beta-cell responsivity indices, the average beta-cell function corrected for insulin resistance was more than 3.5-fold lower in women with glyburide-treated GDM than in healthy pregnant women. Women with GDM in whom glyburide treatment has failed may benefit from alternative medication or dosage escalation; however, fetal safety should be kept in mind.
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“Furthermore, in separate RCTs, glyburide and metformin failed to provide adequate glycemic outcomes in 23% and 25-28% of participants with GDM, respectively (76,77).”
From 15. Management of Diabetes in Pregnancy: Standards of Care in Diabetes—2024 (2024) · cites this paper as [76]
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“Sulfonylureas are known to cross the placenta and have been associated with increased neonatal hypoglycemia.”
From 15. Management of Diabetes in Pregnancy: Standards of Care in Diabetes—2024 (2024) · cites this paper as [76]
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“Concentrations of glyburide in umbilical cord plasma are approximately 50-70% of maternal levels (76,77).”
From 15. Management of Diabetes in Pregnancy: Standards of Care in Diabetes—2024 (2024) · cites this paper as [76]
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“In pregnant women taking glyburide, the umbilical cord glyburide concentration is undetectable (90, 173–176) or, at most, very low (177).”
From Diabetes and Pregnancy: An Endocrine Society Clinical Practice Guideline (2013) · cites this paper as [177]
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Self-citation
Metadata
- Authors
- Hebert, M., Ma, X., Naraharisetti, S., Krudys, K., Umans, J., Hankins, G., Caritis, S., Miodovnik, M., Mattison, D., Unadkat, J., Kelly, E., Blough, D., Cobelli, C., Ahmed, M., Snodgrass, W., Carr, D., Easterling, T., & Vicini, P.
- Affiliations
- University of Washington (US)
- The University of Texas Medical Branch at Galveston (US)
- MedStar Washington Hospital Center (US)
- University of Padua (IT)
- Pfizer (United States) (US)
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2009-03-18
- Volume
- 85
- Issue
- 6
- Pages
- 607-614
- ISSN
- 0009-9236 (ISSN-L)
- 1532-6535
- PMC
- PMC2684566
- OpenAlex
- W1964571629
- Cited by
- 252
- References
- 52
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 8 · 2023: 11 · 2022: 9 · 2021: 32 · 2020: 12 · 2019: 13 · 2018: 16 · 2017: 13 · 2016: 12 · 2015: 21 · 2014: 19 · 2013: 18 · 2012: 16
- FWCI
- 19.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pfizer
- University of Pittsburgh
- National Institutes of Health (UL1TR000423, UL1TR000005)
- National Institute of Biomedical Imaging and Bioengineering (P41EB001975)
- National Center for Research Resources (M01RR023942, M01-RR 00037, UL1RR025014, M01RR020359, M01RR000037)
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U10HD047891, U10HD047892, U10HD047890, U10HD047905)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- gestational diabetes mellitus, glibenclamide, pharmacokinetics, insulin sensitivity, beta-cell function, insulin resistance, mixed meal tolerance test, type 2 diabetes, dose escalation, fetal safety
- MeSH terms
- Adult, Aryl Hydrocarbon Hydroxylases, Blood Glucose, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Female, Fetal Blood, Glyburide, Humans, Hypoglycemic Agents, Insulin Resistance, Metabolic Clearance Rate, Monte Carlo Method, Pregnancy, Pregnancy Trimester, Third, Diabetes, Gestational, Area Under Curve, Insulin-Secreting Cells, Cytochrome P-450 CYP2C9
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