Background

Early pregnancy glycaemic control in women with pre-existing type 2 diabetes (T2DM) is essential in reducing foetal and maternal complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have established benefits for glycaemia and cardiometabolic risk but remain contraindicated in pregnancy and are advised to be ceased once pregnancy is recognised. The metabolic consequences of GLP-1RA cessation in early pregnancy are not well described.

Methods

We report the case of a 39-year-old female G4M3P0 with recurrent early pregnancy losses attributed to poorly controlled T2DM. Following three miscarriages and a HbA1c between 8.7-10.8%, semaglutide was commenced. Clinical, biochemical, and pregnancy outcomes were reviewed.

Results

Commencement of semaglutide pre-conception produced significant metabolic improvements. HbA1c reduced from 10.8% to 7.3% and approximately 15kg of weight was lost within 6 months of commencing semaglutide monotherapy. She subsequently conceived on semaglutide with an early pregnancy HbA1c of 6.9%. Semaglutide was discontinued upon confirmation of pregnancy and insulin commenced. By 13-weeks’ gestation, the patient had regained 15kg of gestational weight. She also developed very severe insulin resistance requiring approximately 750 units of insulin daily by 28-weeks’ gestation despite the addition of metformin and the use of concentrated insulins. Her pregnancy was complicated by heavy proteinuria and the development of pre-eclampsia at 29 weeks’ gestation. While foetal growth and wellbeing have been unremarkable to date, the patient is monitored frequently and will likely have an early planned delivery.

Conclusion

This case highlights the dramatic metabolic deterioration that may occur following abrupt cessation of GLP-1RA therapy in early pregnancy, possible reversing the benefits the woman has obtained. An increasing number of women of reproductive age use GLP-1RAs, and it is expected that exposure in the peri-conception period will increase. Further research is needed to define optimal pre-conception strategies to mitigate rebound weight gain and cardiometabolic deterioration after treatment withdrawal.