Poster Presentation Australasian Diabetes in Pregnancy Society Annual Scientific Meeting 2024

Use of GLP-1 Receptor Agonists in the Preconception Period: Friend or Foe(tus)? (#24)

Natasha Stoinis 1
  1. Endocrinology , Sir Charles Gairdner Hosptial , Perth , Western Australia , Australia

CASE

A 40-year-old female, G5P3 was seen at 12 weeks gestation in the diabetes clinic at King Edward Memorial Hospital in her 4th ongoing pregnancy. The patient developed gestational diabetes in her 3rd pregnancy then type 2 diabetes since 2021. Her first pregnancy was complicated by pre-eclampsia. She struggled with an elevated BMI and was treated for this with Ozempic which was associated with a significant improvement in her HbA1c and metabolic profile. Her HbA1c was 10% pre-Ozempic down to 7.1% in early pregnancy after 6 months of consistent use. This pregnancy was unplanned and she discontinued the weekly injections at 8 weeks gestation as soon as her pregnancy was detected, commencing basal bolus insulin therapy at 11 weeks gestation. So far at 18 weeks gestation, she has had an unremarkable clinical course with no obstetric concerns. She will continue to be monitored closely by both the physician and obstetric teams.

 

CLINICAL QUESTIONS

  1. What is the role of GLP-1 receptor agonists (GLP-1 RA’s) in the preconception period?
  2. These medications are currently contraindicated in pregnancy, is there an ideal washout period/guideline prior to ‘safe’ conception?
  3. In those who fall pregnant on GLP-1 RA’s, are there any known adverse pregnancy outcomes or associated congenital malformations?

 

DISCUSSION 

There is increasing use of GLP-1 RA’s in women of reproductive age particularly with type 2 diabetes and polycystic ovarian syndrome (PCOS). Preconception, they optimise fertility by facilitating weight loss and improved glycaemic control (1,2,3). During this period women should be on reliable contraception as GLP-1 RA’s are contraindicated in pregnancy. More women may therefore unintentionally be on these medications at the time of conception resulting in foetal exposure of uncertain teratogenic risk. Treatment of diabetes in pregnancy is diet, exercise and insulin therapy if required, with metformin and sulfonylureas considered safe in the first trimester. Available literature regarding safety of GLP-1 RA’s in pregnancy is limited to case reports where treatment was discontinued as soon as pregnancy was detected. Currently, there is no significant increased risk of major congenital malformations in exposed pregnancies and GLP-1 RA’s do not appear to cross the placenta with negligible levels detected in umbilical vein samples (2, 4, 5). The associated weight loss and reduced appetite may cause maternal malnutrition and consequently growth restriction in the developing foetus, as seen in animal models (2, 5). Close monitoring and a washout period of at least two months before a planned pregnancy is recommended due to the long half-life of these medications with more longitudinal data required.