Risk-benefit balance with metformin treatment post pregnancy in breastfeeding women - the transfer of metformin into human breast milk and plasma of the child - a low intervention clinical trial protocol

AimsThe primary aim is to determine the concentration of metformin in the plasma of breastfed infants to lactating women being treated for type 2 diabetes. The secondary aim is to determine the concentration of metformin in breast milk and maternal plasma and the milk-to-plasma ratio of the mothers and to calculate the average daily infant dose (ADID) and relative infant dose (RID). MethodsThe study has a low intervention clinical trial design in the sense that breast milk and blood will be collected merely to study excretion of metformin into breastmilk and transferal to her child. Participation in the study will not decide or in any other way interfere with patients treatment as prescribed by their physician. Only patients that already have been assigned treatment with metformin by their physician will be approached and asked for participation. All procedures for blood collection will follow established clinical routines at the clinical sites. The sampling will take place {approx} 6-8 weeks postpartum. The study has been approved as a low-intervention clinical trial by the Swedish Medical Product Agency (Publicly available in CTIS (EU CT no. 2022-501693-19-00 and registered in EUPAS 105190) which includes an approval by the Swedish Ethical Review Authority. The date for the ethics approval is 17 February 2023 ResultsUp to date (24 February) 18 women and infants have been recruited and sampled. Recruitment is ongoing. ConclusionsAn evaluation of pharmacokinetic results as well as clinical experiences related to recruitment and sampling will be systematically conducted upon completion of the study, which is estimated to conclude by the end of 2025. Preliminary experiences suggest that the primary challenge for a study of this nature is recruiting a sufficient number of participants. HighlightsWith as few as 5% of available medications being adequately monitored, tested and labelled with safety information for use in breastfeeding women there is a great need to monitor and evaluate the potential risk of transfer of medicines to the infant. We demonstrate here how a low-intervention clinical trial may be designed in order to provide evidence of transfer.