The full, clinically endorsed recommendation should be obtained from Lareb.   

Rationale for drug selection  

Metformin is used for gestational diabetes mellitus and (pre‑gestational) type 2 diabetes in pregnancy. It is known that pregnancy alters pharmacokinetics. Therefore, dose adjustments might be needed to maintain adequate glycaemic control.

Pharmacokinetics of metformin in pregnancy 

During pregnancy, both renal blood flow and glomerular filtration are elevated, which leads to an increased renal clearance of metformin. This may result in lower plasma concentrations during pregnancy. As a result, pregnant patients may need a higher dose to maintain efficacy. Placental transfer of metformin occurs, and foetal concentrations can approximate maternal levels. Across studies, maternal metformin concentrations are decreased by about 20–35% during the third trimester of pregnancy. These alterations in plasma concentrations were also confirmed by maternal PBPK models, which provided strong evidence on the influence of gestation on the pharmacokinetics of metformin. These models were used for dosing and support decision making.

Benefits and risks with the proposed dose adjustments 

The expected benefits and associated risk of a higher maximum dose of metformin during pregnancy.

In short 

Metformin is prescribed for gestational diabetes and diabetes type 2 during pregnancy. Renal clearance increases during pregnancy, which reduces metformin exposure. Hence, dose adjustments may be needed, but should not unnecessarily prolong time to adequate glucose control. Based on the weighing of benefits and risks, the working committee derived an appropriate dose adjustment. Consult Lareb for the model-informed dosing recommendations.