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 (AUC(0-4)) and 0 to 8 h post-dose (AUC(0-8)) 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) AUC(0-4) that was 69% (53.6, 84.8) of the postpartum value. The AUC(0-4) of one subject was higher in pregnancy at 142% of the postpartum value. Overall, the mean (95% CI) AUC(0-4) 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.