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Pharmacodynamics of Glyburide, Metformin, and Glyburide/Metformin Combination Therapy in the Treatment of Gestational Diabetes Mellitus
Author(s) -
Shuster Diana L.,
Shireman Laura M.,
Ma Xiaosu,
Shen Danny D.,
Flood Nichols Shan K.,
Ahmed Mahmoud S.,
Clark Shan,
Caritis Steve,
Venkataramanan Raman,
Haas David M.,
Quinney Sara K.,
Haneline Laura S.,
Tita Alan T.,
Manuck Tracy A.,
Thummel Kenneth E.,
Brown Linda Morris,
Ren Zhaoxia,
Brown Zane,
Easterling Thomas R.,
Hebert Mary F.
Publication year - 2020
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1749
Subject(s) - metformin , medicine , gestational diabetes , pharmacodynamics , combination therapy , diabetes mellitus , glibenclamide , insulin , endocrinology , insulin resistance , pregnancy , pharmacology , gestation , pharmacokinetics , biology , genetics
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.