Diabetes Dialogue: Latest Updates on Diabetes Management in Pregnancy

Despite the impact on public health, management of maternal diabetes remains an understudied field within healthcare. In this episode of Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, breakdown as pair of recent studies examining management of diabetes during pregnancy.

The first study discussed in the episode was an analysis of more than 50,000 patients from the International Pregnancy Safety Study (InPreSS) Consortium assessing the impact of periconceptional exposure to second-line noninsulin antidiabetes medication on risk of major congenital malformations (MCMs) in the infant. The second study is a randomized clinical trial examining the use of metformin relative to placebo therapy for a composite of neonatal complication.

Safety of Second-Line Antidiabetes Medications in Early Pregnancy

However, as investigators outline, their risk on MCMs is not well studied. To further examine the topic, the current study’s population included data from pregnant women with type 2 diabetes and live0-born infants from 4 Nordic countries (2009-2020), the US MarketScan Database (2012-2021), and the Israeli Maccabi Health Services database (2009-2020).¹

Investigators aimed to assess periconceptional exposure to sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors relative to insulin on risk of any MCM from date of birth to a year after birth in the Nordic and Israeli cohorts and from birth to 90 days after birth in the US cohort. Investigators pointed out risk was estimated using log-binomial regression models, adjusting for key confounders in each cohort.¹

Results suggested the following relative risk (RR) for MCMs associated with each class compared with insulin:¹

• Sulfonylureas: RR, 1.18; 95% CI, 0.94 – 1.48
• GLP-1 agonists: RR, 0.95; 95% CI, 0.72 – 1.26
• SGLT-2 inhibitors: RR, 0.98; 95% CI, 0.65 – 1.46
• DPP-4 inhibitors: RR, 0.83; 95% CI, 0.64 – 1.06

MOMPOD

The Medical Optimization of Management of Overt Type 2 Diabetes in Pregnancy (MOMPOD) trial was designed as a multicenter, double-blind, randomized controlled trial to assess whether adding metformin to insulin among pregnant women might lower risk of perinatal death or serve complications relative to insulin alone. The trial enrolled patients with preexisting type 2 diabetes or gestational diabetes diagnosed in early pregnancy from 17 US clinical sites with oversight from the US Food and Drug Administration.²

For inclusion, patients needed to be aged 18 to 45 years with a singleton gestation between 10 weeks 0 days and 22 weeks 6 days, confirmed by ultrasound with either preexisting type 2 diabetes or with diabetes identified before 23 weeks requiring insulin. The trial enrolled 831 pregnant adults, including 794 who received at least 1 dose of the study agent, with 397 patients in both the insulin-only and metformin plus insulin groups included in the primary analysis.²

The study was halted at 75% accrual for futility in detecting a significant difference in the primary outcome. Results of the study suggested the composite adverse neonatal outcome, which included perinatal death, preterm birth, large or small for gestational age, and hyperbilirubinemia requiring phototherapy, occurred in 71% of the metformin group and among 74% of the placebo group (adjusted odds ratio, 0.86; 95% CI 0.63-1.19). Investigators pointed out metformin-exposed neonates had reduced odds of being large for gestational age (adjusted odds ratio, 0.63; 95% CI, 0.46-0.86) when compared with the insulin-only group.²

Relevant disclosures for Dr. Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Dr. Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.

References:

1. 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. Published online December 11, 2023. doi:10.1001/jamainternmed.2023.6663
2. Boggess KA, Valint A, Refuerzo JS, et al. Metformin Plus Insulin for Preexisting Diabetes or Gestational Diabetes in Early Pregnancy: The MOMPOD Randomized Clinical Trial. JAMA. 2023;330(22):2182–2190. doi:10.1001/jama.2023.22949