Unplanned pregnancy risks flagged for GLP-1s

Researchers have warned that many women taking glucagon-like peptide-1 (GLP-1) receptor agonists may be unaware of the associated risks of unplanned pregnancy, or potential foetal risks linked to the medications.
 
The new research from Flinders University analysed data from more than 1.6 million women aged 18–49 who attended general practices between 2011 and 2022.
 
It revealed that of the 18,010 women in that cohort who were first prescribed GLP-1 medications during that time, only 21% reported using contraception, and 2.2% of women became pregnant within six months of starting GLP-1 treatment.
 
The findings serve as a ‘good reminder’ for GPs to routinely discuss reproductive health plans with women wanting GLP-1 therapy, said Chair of RACGP Specific Interests Antenatal and Postnatal Care, Dr Ka-Kiu Cheung.

‘With the increasing use of GLP-1 receptor agonists for type 2 diabetes and weight management, it is important that GPs actively address reproductive health considerations in women of child-bearing age,’ she told newsGP. 
 
The prescribing of GLP-1 receptor agonists for women of reproductive age is increasing in Australia, and most prescriptions are for women not diagnosed with type 2 diabetes.
 
In the Flinders University study, of the 6954 women first prescribed GLP-1 receptor agonists during 2022, 90.5% did not have type 2 diabetes, suggesting that many were using the medication for weight loss.
 
GLP-1 receptor agonists such as semaglutide (marketed as Ozempic and Wegovy) and dual GIP/GLP-1 agonist tirzepatide (Mounjaro) have become increasingly popular for weight loss in both women and men.
 
Australia’s Therapeutic Goods Administration (TGA) has approved semaglutide, dulaglutide and liraglutide for managing type 2 diabetes in adults, while tirzepatide is TGA-approved for the management of both type 2 diabetes and chronic weight management.
 
Dr Cheung said that unintended pregnancy linked to GLP-1 medications ‘has been on the radar for some time, given nearly half of all pregnancies in Australia are unplanned’. 
 
She said the study suggested one of the main factors behind GLP-1 medications’ link to a rise in unplanned pregnancies is likely to be the improved fertility associated with weight loss – especially in women with anovulatory cycles such as those with polycystic ovary syndrome.  
 
She also cited concerns that medications such as tirzepatide could also reduce the effectiveness of oral contraceptives by reducing their absorption.
 
Chair of RACGP Specific Interests Obesity Management, GP and dietitian, Dr Terri-Lynne South, agrees that the study shows a potential reduction in reliability of oral contraceptives due to the delay in gastric emptying caused by the medications, but stressed the word ‘potential’.
 
‘If there is any significant delay in the absorption of the drug, it affects its pharmacokinetics and therefore potentially its reliability,’ Dr South told newsGP.
 
While one study has suggested GLP-1 receptor agonists could cut the efficacy of oral contraception, this has been queried in another study.
 
Dr South said the risk appears to be greatest when people first start taking the medication, or when increasing their dosage, but that a significant delay in gastric emptying ‘is not there a year down the track’.
 
Contraception is also recommended for women of child-bearing age using GLP-1s because of safety concerns raised by animal studies linking exposure of the medication during pregnancy to reduced foetal growth, slowed bone development and reduced maternal weight gain.
 
Acknowledging limited human data, the study’s lead author Associate Professor Luke Grzeskowiak said the potential risks are ‘concerning’.
 
‘Whilst the UK advises that women using GLP-1 receptor agonists should avoid pregnancy and use effective contraception, this advice is not being followed consistently in Australian clinical practice,’ he said.
 
‘We’re seeing widespread use of these medications among women of childbearing age, but very little evidence that contraception is being considered as part of routine care.
 
‘These medications can be incredibly helpful, but they’re not risk-free, especially during pregnancy.’
 
Dr South said it is ‘good news’ that women who had accidentally become pregnant on the lower dose of semaglutide (Ozempic) had not seen any ‘significant teratogenic effects’ in their babies.
 
However, she said more research was needed – particularly around pre-conception epigenetic effects of the medication in both women and men.
 
‘I do feel that we need more data about the use of these medications in the epigenetic influence on the development of sperm and egg, which is potentially happening three months before that egg is actually conceived,’ she said.
 
Both Dr South and Dr Cheung agree on the importance of GPs discussing family planning with women of child-bearing age who are undergoing GLP-1 treatment.
 
‘My advice to clinicians is to proactively discuss contraception when initiating GLP-1 therapies in women of child-bearing age, document pregnancy intentions, and give pre-conception wash-out advice as per FSRH guidelines,’ said Dr Cheung.
 
‘I think GPs need to understand that, yes, the medication is contraindicated in pregnancy. Therefore, they need to know what their patient’s contraception current use is, and in the context of family planning as well,’ said Dr South.
 
‘And if there is family planning, that the medication should be stopped at least two months prior to removing contraception or trying to conceive.’
 
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