Effect of pregnancy on the pharmacokinetics of metformin

Diabet Med. 2006 Mar;23(3):323-6. doi: 10.1111/j.1464-5491.2005.01769.x.

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.

MeSH terms

  • Adult
  • Area Under Curve
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Administration Schedule
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / blood
  • Hypoglycemic Agents / pharmacokinetics*
  • Metformin / administration & dosage
  • Metformin / blood
  • Metformin / pharmacokinetics*
  • Postpartum Period
  • Pregnancy
  • Pregnancy Trimester, Third
  • Pregnancy in Diabetics / drug therapy*
  • Pregnancy in Diabetics / metabolism

Substances

  • Hypoglycemic Agents
  • Metformin