In T2DM, periconceptional, noninsulin, second-line antidiabetes medications were not linked to major congenital malformations vs. insulin
A new study provides some reassurance to patients who unintentionally become pregnant while taking diabetes drugs but should be interpreted with caution because the number of infants exposed was low and only pregnancies resulting in live births were included, an ACP Journal Club commentary said.
In-utero exposure to second-line noninsulin antidiabetes medications (ADMs) does not appear to significantly increase risk of major congenital malformations (MCMs), an international study found. The study included 51,826 pregnancies in type 2 diabetes (T2DM) patients. Their overall rate of MCM was 5.3%, compared to 9.7% with exposure to sulfonylureas, 6.1% with dipeptidyl peptidase-4 inhibitors, 8.3% with glucagon-like peptide-1 receptor agonists, 7.0% with sodium-glucose cotransporter-2 inhibitors, and 7.8% with insulin. For comparison, the standardized prevalence of MCMs was 3.7% in all infants (n=3,514,865).
The study was published by JAMA Internal Medicine on Dec. 11, 2023. The following commentary by Aoife M. Egan, MB BCh BAO, PhD, was published in the ACP Journal Club section of Annals of Internal Medicine on April 2.
Insulin is the preferred pharmacologic agent for patients with T2DM who are pregnant or are planning pregnancy, primarily because there is limited information on the safety profiles of alternative ADMs. Metformin is an exception, because it has reassuring safety data in early pregnancy and can be considered on an individual basis to treat pregnant patients with T2DM.
Outside of pregnancy, use of glucagon-like peptide-1 receptor agonists and other noninsulin second-line ADMs has increased due to their glycemic and extra-glycemic benefits. This has resulted in unintentional exposure during unplanned pregnancies. In their population-based cohort study, Cesta and colleagues found that, although maternal T2DM was associated with increased risk for MCMs, periconceptual use of second-line ADMs was not linked to additional increased risk. They also found that MCMs were lowest among infants with no ADM exposure or exposure to metformin only and highest with exposure to sulfonylureas. The relative risk of second-line agents compared with metformin was not explored.
The study results should be interpreted with some caution because the number of infants exposed was low and this resulted in imprecise risk estimates. Further, only pregnancies that resulted in live births were included, and MCMs that resulted in abortion were not captured, potentially underestimating risk. This requires further study, particularly in light of animal and human data reporting associations of second-line ADMs with MCMs and pregnancy loss. The study did not assess the relative risk of other important outcomes, such as maternal or neonatal hypoglycemia, or infants who were large or small for gestational age.
Overall, the study supports ongoing use of metformin alone or with insulin in pregnancy affected by T2DM. Given the absence of major teratogenic effects, these data also provide some reassurance to individuals who unintentionally become pregnant while receiving second-line, noninsulin ADMs. However, until further studies are completed, these medications should continue to be discontinued periconceptually.