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

Diana L. Shuster; Laura M. Shireman; Xiaosu Ma; Danny D. Shen; Shannon K. Flood Nichols; Mahmoud Ahmed; Shannon Clark; Steve Caritis; Raman Venkataramanan; David M. Haas; Sara K. Quinney; Laura S. Haneline; Alan T. Tita; Tracy A. Manuck; Kenneth E. Thummel; Linda Morris Brown; Zhaoxia Ren; Zane Brown; Thomas R. Easterling; Mary F. Hebert

doi:10.1002/cpt.1749

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

Diana L. Shuster, Laura M. Shireman, Xiaosu Ma, Danny D. Shen, Shannon K. Flood Nichols, Mahmoud Ahmed, Shannon Clark, Steve Caritis, Raman Venkataramanan, David M. Haas, Sara K. Quinney, Laura S. Haneline, Alan T. Tita, Tracy A. Manuck, Kenneth E. Thummel, Linda Morris Brown, Zhaoxia Ren, Zane Brown, Thomas R. Easterling, Mary F. Hebert

Obstetrics & Gynecology

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1362-1372
Number of pages	11
Journal	Clinical Pharmacology and Therapeutics
Volume	107
Issue number	6
DOIs	https://doi.org/10.1002/cpt.1749
State	Published - Jun 1 2020

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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Shuster, D. L., Shireman, L. M., Ma, X., Shen, D. D., Flood Nichols, S. K., Ahmed, M., Clark, S., Caritis, S., Venkataramanan, R., Haas, D. M., Quinney, S. K., Haneline, L. S., Tita, A. T., Manuck, T. A., Thummel, K. E., Brown, L. M., Ren, Z., Brown, Z., Easterling, T. R., & Hebert, M. F. (2020). Pharmacodynamics of Glyburide, Metformin, and Glyburide/Metformin Combination Therapy in the Treatment of Gestational Diabetes Mellitus. Clinical Pharmacology and Therapeutics, 107(6), 1362-1372. https://doi.org/10.1002/cpt.1749

Shuster, DL, Shireman, LM, Ma, X, Shen, DD, Flood Nichols, SK, Ahmed, M, Clark, S, Caritis, S, Venkataramanan, R, Haas, DM, Quinney, SK, Haneline, LS, Tita, AT, Manuck, TA, Thummel, KE, Brown, LM, Ren, Z, Brown, Z, Easterling, TR & Hebert, MF 2020, 'Pharmacodynamics of Glyburide, Metformin, and Glyburide/Metformin Combination Therapy in the Treatment of Gestational Diabetes Mellitus', Clinical Pharmacology and Therapeutics, vol. 107, no. 6, pp. 1362-1372. https://doi.org/10.1002/cpt.1749

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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.",

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AU - Manuck, Tracy A.

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AU - Ren, Zhaoxia

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AU - Easterling, Thomas R.

AU - Hebert, Mary F.

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

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