Additional preconception considerations for patients with diabetes

Letter

I thank Callaway and Britten for their article on management of pre-existing diabetes prior to and during pregnancy.¹ I would be grateful to make the following comments.

Preconception screening in patients with diabetes should include consideration of obstructive sleep apnoea (OSA), especially in women with obesity, polycystic ovarian syndrome, hypertension or autonomic neuropathy, given the association of OSA with pre-eclampsia, hypertension, low birthweight infants, premature delivery and stillbirth.²

In women with diabetes and comorbidities associated with obesity (e.g. OSA, hypertension, reduced fertility), the potential benefits of bariatric surgery before conception may be discussed, while considering the risk of small-for-gestational-age infants. Most guidelines recommend women delay pregnancy for 12 to 24 months following bariatric surgery; however, observational studies suggest that time from bariatric surgery to birth does not affect neonatal outcomes.³

Glibenclamide has been used in all trimesters of pregnancy for 40 years without evidence of teratogenicity, and may be an alternative to insulin in women with type 2 diabetes and severe needle phobia, provided glycaemic control is satisfactory.⁴

While newer antihyperglycaemic medications should be stopped before conception, a recently published study on teratogenic risk may provide some reassurance for women with unplanned pregnancy who are taking glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose co-transporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors.⁵

Adam Morton
Senior Staff Specialist in Endocrinology and Obstetric Medicine, Queensland Diabetes and Endocrine Centre, Mater Health, Brisbane

Conflicts of interest: none declared

 

References

1. Callaway LK, Britten F. Managing pre-existing diabetes prior to and during pregnancy. Australian Prescriber 2024;47:2-6.
2. Morton A. Comorbidities of obesity and preconception counselling: Consideration of bariatric surgery. Aust J Gen Pract 2022;51:631-5.
3. Rottenstreich A, Levin G, Kleinstern G, Rottenstreich M, Elchalal U, Elazary R. The effect of surgery-to-conception interval on pregnancy outcomes after sleeve gastrectomy. Surg Obes Relat Dis 2018;14:1795-803.
4. Raets L, Ingelbrecht A, Benhalima K. Management of type 2 diabetes in pregnancy: a narrative review. Front Endocrinol (Lausanne) 2023;14:1193271.
5. Cesta CE, Rotem R, Bateman BT, Chodick G, Cohen JM, Furu K, et al. Safety of GLP-1 Receptor Agonists and Other Second-Line Antidiabetics in Early Pregnancy. JAMA Intern Med 2024;184:144-52.

 

Authors’ response

Leonie Callaway and Fiona Britten, the authors of the article, comment:

We thank Morton for his insightful comments. We agree it is important to screen selected larger-bodied patients with diabetes for OSA, and to provide counselling on bariatric surgery before conception and, for women who have undergone bariatric surgery, appropriate monitoring during pregnancy.

While the sulfonylurea glibenclamide has been used in practice without evident teratogenesis, a meta-analysis of randomised controlled trials (RCTs) examining its use (compared with insulin or metformin) raised concerns for increased perinatal complications including neonatal hypoglycaemia.¹ Importantly, RCT data examining long-term infant outcomes after exposure to sulfonylureas (in comparison with insulin) are not available. Given the availability of insulin, a drug that does not cross the placenta, to successfully treat type 2 diabetes in pregnancy, all other drugs that cross the placenta should meet a stringent safety threshold before being routinely recommended in pregnancy. Metformin crosses the placenta, but has been studied in RCTs with long-term follow-up of exposed infants.^2,3

Recent data suggesting GLP-1 receptor agonists, DPP-4 inhibitors and SGLT2 inhibitors may not be teratogenic are reassuring for women who have inadvertently conceived on these drugs.⁴ Until there is better quality research, including long-term infant follow-up, it remains important to emphasise that women should use contraception while taking these drugs, access preconception care and stop these drugs before conception.

 

References 2

1. Balsells M, Garcia-Patterson A, Sola I, Roque M, Gich I, Corcoy R. Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis. BMJ 2015;350:h102.
2. Feig DS, Sanchez JJ, Murphy KE, Asztalos E, Zinman B, Simmons D, et al. Outcomes in children of women with type 2 diabetes exposed to metformin versus placebo during pregnancy (MiTy Kids): a 24-month follow-up of the MiTy randomised controlled trial. Lancet Diabetes Endocrinol 2023;11:191-202.
3. Rowan JA, Rush EC, Plank LD. Metformin in Gestational Diabetes The Offspring Follow Up (MiGTOFU): Associations between maternal characteristics and size and adiposity of boys and girls at nine years. Aust N Z J Obstet Gynaecol 2023;63:825-8.
4. Cesta CE, Rotem R, Bateman BT, Chodick G, Cohen JM, Furu K, et al. Safety of GLP-1 Receptor Agonists and Other Second-Line Antidiabetics in Early Pregnancy. JAMA Intern Med 2024;184:144-52.

 

The Editorial Advisory Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by any responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.