What the Future of Treating Gestational Diabetes May Look Like
By Susannah Chen
What’s on the horizon for treating gestational diabetes? From tech-driven diagnostic tools to potential therapies for GDM, here’s a look at what the future may hold for GDM treatment.
Gestational diabetes – a type of diabetes where blood glucose levels are higher than normal during pregnancy – is a common condition that is estimated to affect between 2% and 10% of pregnancies. It can lead to serious health consequences, including a significantly increased risk of type 2 diabetes and chronic kidney disease later in life for the mother, and large birth weight, preterm birth, and other complications for the newborn child.
Experts recommend that people with diabetes aim for a narrower time in range target – 63-140 mg/dl 85% percent of the time, versus 70-180 mg/dl 70% of the time – and those with gestational diabetes also need special attention during pregnancy.
In comparison to the lightning-fast therapy pipeline for type 2 diabetes and the rapidly evolving technologies for type 1 diabetes, treatment for gestational diabetes mellitus (GDM) has remained relatively stagnant throughout the years.
In the United States, pregnant individuals are typically screened for GDM by a glucose challenge test and an oral glucose tolerance test (OGTT). If a person has been diagnosed with GDM, lifestyle modifications like more frequent exercise and a lower-carb diet are often recommended to achieve stringent blood glucose time in range goals. If that does not sufficiently improve time in range, then insulin therapy is the standard treatment.
At the moment, only two blood glucose-lowering treatments – insulin and metformin – are approved for use during pregnancy, along Dexcom and Freestyle Libre CGM devices. But thanks to new technologies, the advocacy of a number of perinatal diabetologists, and several recently presented clinical trials, gestational diabetes treatment and indications for use in certain diabetes technologies could soon see a significant change.
Possible changes in the screening of gestational diabetes
Many in the U.S. follow the recommendations of the U.S. Preventive Services Task Force to conduct an oral glucose challenge test followed by an oral glucose tolerance test around 24 weeks of gestation. Nevertheless, there is currently no worldwide consensus on the best method for screening for GDM, when testing should be completed, and what glucose thresholds should be used to diagnose GDM. While a number of researchers have advocated for a GDM screening standard across the board, the international diabetes community has not yet been able to come to an agreement on diagnostics for gestational diabetes.
Technology: A potential game-changer for GDM diagnostics
The most commonly used tests for diagnosing gestational diabetes, the glucose challenge test and the OGTT, have a number of challenges, including the fact that they only offer a snapshot of blood glucose levels at one point in time, and that they do not always produce the same results when used repeatedly.
Enter continuous glucose monitors (CGMs), which could potentially change the conversation when it comes to testing for and diagnosing gestational diabetes. Given that CGMs have become increasingly accurate and are able to track blood glucose levels every few minutes, they could hold the keys to earlier, more accurate detection of gestational diabetes.
The promising case for CGM in early GDM detection
Dr. Celeste Durnwald, who is the director of the Perinatal Diabetes Program at Penn Medicine, discussed this topic at ATTD 2024. She went over the results of the GLAM study, which demonstrated that CGM patterns in early pregnancy can identify problems with blood glucose levels well before the OGTT is typically used for screening.
Durnwald also cited the TOBOGM study, a trial investigating the impact that early treatment of GDM had on maternal and fetal outcomes. In TOBOGM, pregnant individuals who received immediate treatment for GDM had less risk than they would have otherwise (a 25% risk compared to 30% risk in a control group). The TOBOGM study demonstrated that if CGM could be used early to identify who’s at risk, it might make a significant difference.
How realistic is using CGM for early gestational diabetes detection?
Could CGM be the eventual go-to for diagnosing gestational diabetes? Durnwald maintained that initial data from these studies holds promise, especially because early intervention could be the difference between positive and adverse perinatal outcomes. Durnwald pointed out that an interventional trial comparing use of a CGM versus benign treatment – one that includes a clinically meaningful threshold to identify people with blood glucose management issues early in pregnancy – would be needed as a next step.
A takeaway from type 1 pregnancy studies: early monitoring is crucial
Dr. Eleanor Scott, a professor and clinician focused on diabetes and maternal health at the University of Leeds School of Medicine, combined the data from CONCEPTT – a type 1 diabetes pregnancy study that showed CGM use in pregnancy benefited both mothers and their newborns – along with a Swedish observational study to conduct a new analysis exploring the relationship between CGM glucose trajectories and infants who are born large and small for their gestational age birth weights.
Scott’s analysis revealed just how crucially important it is for pregnant people with diabetes to manage their blood glucose in the first trimester of pregnancy – specifically, beginning between 10 and 12 weeks, in order to achieve healthy fetal growth and normal birth weight outcomes.
While the studies analyzed were both type 1 diabetes pregnancy studies, Scott maintained that these findings have takeaways for treatment of gestational diabetes, too.
“We have done some work in birth weight outside of type 1 diabetes pregnancy that tells us that actually, when you look at the CGM profiles, what we were missing with regards to large gestational age babies was that women [birthing larger babies] were running a higher CGM glucose overnight – and we aren’t detecting it in current fingerstick monitoring,” Scott said.
Clinicians who treat GDM patients, Scott maintained, need to place a greater emphasis on weekly glucose targets to optimize blood glucose management early on in the first trimester of a pregnancy, as this could directly determine birth outcomes.
Other medications besides insulin could play a greater role in treating gestational diabetes
Only two medications are currently being used to treat gestational diabetes: insulin and metformin. Insulin plays a foundational role in managing gestational diabetes. Metformin, while sometimes used to treat GDM, hasn’t been the therapeutic standard of care for diabetes during pregnancy because the medication crosses the placenta, passing along its effects to the fetus.
Metformin as a potential first-line treatment for gestational diabetes
Recently published research, however, has suggested that metformin could be comparable to insulin in GDM treatment while also leading to higher patient satisfaction. Additional large-scale studies are needed to understand metformin’s safety and efficacy in gestational diabetes, but this suggests that there could be room for another standard treatment option.
Could inhaled insulin be next on the approved list for GDM?
MannKind, the company that manufactures the inhaled insulin Afrezza, also expressed recent interest in exploring obtaining FDA approval to treat gestational diabetes. “As people are starting to see the first dose data, we're getting questions on gestational diabetes,” Michael Castagna, MannKind’s CEO, said.
MannKind is currently running two trials, INHALE-1 and INHALE-3, that are studying the use of Afrezza in various populations, including children with type 1 or type 2 diabetes, and adults with type 1 diabetes, respectively. Initial topline results for both studies are expected later this year.
In order for a regulatory body such as the FDA to approve a new indication for a drug, additional clinical data will be needed to show that the drug can safely and effectively treat patient populations other than those for which it was originally intended. Could Afrezza’s makers have been hinting that a gestational diabetes trial could come next?
“We think there's an unmet need there that we want to fulfill over time, because there's only two drugs that can be used today: metformin, which crosses the placenta, and slow-acting injectable insulin,” Castagna said, adding: “Anyone [who’s] suffered from gestational diabetes knows keeping your time in range really tight is critically important.”
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Photo credits: iStock (top); MannKind (bottom).
