Pharmacodynamics of Metformin in Pregnant Women With Gestational Diabetes Mellitus and Nonpregnant Women With Type 2 Diabetes Mellitus

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.

Keywords: disposition index; gestational diabetes mellitus; insulin sensitivity; metformin; pharmacodynamics; pregnancy; type 2 diabetes mellitus; β-cell responsivity.

Figure 1.. Pharmacodynamic effects of metformin in women with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM).

Mean disposition index for all adherent subjects who completed the study in the GDM metformin arm at baseline (solid gray line) and on study day 2 (dashed gray line) as well as for subjects with T2DM at baseline (solid black line) and on study day 2 (dashed black line). The vectors depict the mean pharmacodynamic effect of metformin in subjects with GDM (gray arrow) and subjects with T2DM (black arrow). Solid dots represent mean baseline disposition index (study day 1) and open circles represent study day 2 mean disposition index (GDM corrected for mean gestational age-dependent change).