Effect of pregnancy on the pharmacokinetics of metformin

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Abstract
Aims  To determine the effects of pregnancy on metformin pharmacokinetics.Methods  Seven women with Type 2 diabetes mellitus taking metformin throughout pregnancy were studied on two occasions, once at 28–36 weeks gestation and once at least 8 weeks postpartum. Serum metformin concentrations were determined across a dosing interval using high‐performance liquid chromatography. The areas under the serum concentration‐time curve from 0 to 4 h post‐dose (AUC0−4) and 0 to 8 h post‐dose (AUC0−8) where possible, were compared in the pregnant and non‐pregnant state.Results  Metformin concentrations were lower in pregnancy in six subjects, with a mean (95% CI) AUC0−4 that was 69% (53.6, 84.8) of the postpartum value. The AUC0−4 of one subject was higher in pregnancy at 142% of the postpartum value. Overall, the mean (95% CI) AUC0−4 during pregnancy for all seven subjects was 80% (51.3, 107.8) of the postpartum value (P = 0.053, two‐tailed t‐test; P = 0.027, one‐tailed t‐test).Conclusion  These results are consistent with our hypothesis that the clearance of metformin increases in pregnancy as a result of enhanced renal elimination. A larger study is required to establish whether metformin dose adjustments are required in late pregnancy to maintain therapeutic effect.

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