Safety of GLP-1 agonists and other second-line diabetes meds in early pregnancy

The teratogenic risk of using second-line noninsulin medications for type 2 diabetes during pregnancy is unknown. However, this is an important issue as usage of these agents is increasing with the rise of type 2 diabetes in female individuals of reproductive age. Metformin is often the first-line pharmacologic treatment for type 2 diabetes. If additional glycemic control is needed, insulin or other second-line noninsulin antidiabetes medications (e.g., sulfonylureas, dipeptidyl peptidase 4 [DPP-4] inhibitors, glucagon-like peptide 1 [GLP-1] receptor agonists, sodium-glucose cotransporter 2 [SGLT2] inhibitors), can be added or used as alternatives.Traditionally, insulin has been the guideline-recommended treatment for type 2 diabetes in pregnancy, due to limited safety data for noninsulin medications. However, the intentional use of metformin during pregnancy has become more common and unintended exposure to second-line noninsulin antidiabetes medications during the first trimester has also increased over time. Unintentional exposure to these agents during pregnancy may arise because a proportion of pregnancies are unplanned. To study this issue, a new trial examined whether periconceptional use of second-line noninsulin antidiabetes medications is associated with increased risk of major congenital malformations in the infant. The observational population-based cohort study used data from four Nordic countries (2009–2020), the United States (2012–2021) and Israel (2009–2020). Pregnant women with type 2 diabetes were identified and their live-born infants were followed for up to one year after birth.Periconceptional exposure was defined as one or more prescription fill of a sulfonylurea, DPP-4 inhibitor, GLP-1 receptor agonist and SGLT2 inhibitor, or insulin (active comparator) from 90 days before pregnancy to the end of the first trimester.Results showed the following:Periconceptional exposure to second-line noninsulin antidiabetes medications differed between countries, with 32 exposures in the Nordics, 295 in the US and 73 in Israel per 100,000 pregnancies, respectively). It also increased over the study period, particularly for GLP-1 receptor agonists in the United States. The prevalence of major congenital malformations in all infants in the general population was 3.7% (n=3,514,865) and 5.3% in the infants born to women with type 2 diabetes (n=51,826). The prevalence of major congenital malformations among infants exposed to sulfonylureas was 9.7% (n=1,362); DPP-4 inhibitors, 6.1% (n=687); GLP-1 receptor agonists, 8.3% (n=938); SGLT2 inhibitors, 7.0% (n=335); and insulin, 7.8% (n=5,078). Compared with insulin, adjusted relative risks (RRs) for major congenital malformations were 1.18 (95% CI, 0.94–1.48) for infants exposed to sulfonylureas, 0.83 (95% CI, 0.64–1.06) for DPP-4 inhibitors, 0.95 (95% CI, 0.72–1.26) for GLP-1 receptor agonists and 0.98 (95% CI, 0.65–1.46) for SGLT2 inhibitors.Read: New website addresses safety of meds and substances during pregnancy/lactationThe investigators concluded that use of second-line noninsulin antidiabetes medications is rapidly increasing for treatment of type 2 diabetes (and other indications), resulting in an increasing number of exposures during pregnancy. Although the authors acknowledge that some estimates were imprecise, their results do not indicate a large increased risk of major congenital malformations above the risk conferred by maternal type 2 diabetes requiring second-line treatment. Although these results are reassuring, confirmation from other studies is needed. In addition, continuous monitoring to accumulate more data will provide more precise estimates of the safety of second-line noninsulin antidiabetes medications during pregnancy. Reference1. Cesta CE, Rotem R, Bateman BT, et al. Safety of GLP-1 receptor agonists and other second-line antidiabetics in early pregnancy. JAMA Intern Med 2023;doi:10.1001/jamainternmed.2023.6663. Published online December 11, 2023. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2812743#:~:text=Findings%20This%20multinational%20population%2Dbased,or%20sodium%2Dglucose%20cotransporter%202 (accessed December 13, 2023). Read: Safe to take? New UofT program to provide info on exposures to medications during pregnancy and lactation.

Safety of GLP-1 agonists and other second-line diabetes meds in early pregnancy

Register for free access or login.

Related Topics