Here’s How CGM Is Transforming Clinical Trials

For decades, clinical trials have played a key role in preventing, managing (and hopefully one day, curing) diabetes. These trials are responsible for developing tools people with diabetes rely on daily – like automated insulin delivery (AID) systems, new medications, behavioral programs, and more. 

Since the A1C test was developed in the mid-1970s, it became the go-to measurement in clinical trials to evaluate blood sugar levels. More recently, however, one type of diabetes technology has taken an important role in supplementing A1C by providing even more detailed information about blood sugar: continuous glucose monitoring (CGM). 

CGM has been around for more than two decades. However, as these devices have become more accurate and central to diabetes care, the role of CGM in studying new treatments for diabetes continues to grow.

“It is important to keep in mind that CGM is currently the standard of care for individuals with type 1 diabetes and those with type 2 diabetes treated with insulin. So any trial involving these cohorts must include CGM,” said Dr. Roy Beck, a physician and epidemiologist who coordinates clinical trials at the Jaeb Center for Health Research.

According to a 2021 study, the use of CGM to study diabetes treatments grew from less than 5% of trials in 2005 to 12.5% in 2019 – and continues to increase. In 2022, a group of global experts provided recommendations to standardize the way CGM data is collected and reported. Since then, researchers have increasingly incorporated CGM into their research, allowing studies to include the same metrics people with diabetes and their clinicians use every day, like time in range.

A number of presentations on new treatments this year at scientific conferences highlighted the increasing use of CGM in clinical trials, from a study of inhaled insulin in adults with type 1 diabetes to the QWINT trials evaluating the once-weekly insulin efsitora.

“In my opinion, all research in type 1 and type 2 diabetes should include CGM. It’s not appropriate not to provide standards of care to participants volunteering their time for research,” said Dr. Viral Shah, an endocrinologist and associate professor of medicine and pediatrics at the IU Center for Diabetes and Metabolic Diseases at Indiana University. “Inclusion of CGM in research has many advantages for both participants as well as sponsors.”

A more detailed picture of how treatments work

CGM collects important data to show how treatments impact participants. CGM-collected metrics like time in range, time above range, and time below range provide additional information to show if a new treatment affects blood sugars, how quickly it takes effect, and if those effects vary between doses. In contrast, A1C only provides an estimate of average blood sugar over the previous two- to three-month period.

“A1C remains a good metric for assessing the overall amount of hyperglycemia during a three-month period and for trials in which the goal of therapy is to reduce hyperglycemia over at least a three-month period,” Beck said. “However, that is where its value ends. A1C provides no information on the frequency or severity of hypoglycemia or glucose variability, which are readily measured with CGM. Additionally, CGM provides key information on the pattern of glucose levels and when highs and lows occur.” 

All this information can help make sure treatments are used safely and effectively. In an update to guidance for conducting clinical trials, the FDA noted that CGM data helps assess hypoglycemia risk associated with a treatment more effectively than is possible with traditional methods like fingerstick testing. This is because CGM is more likely to capture all low blood sugars – not just lows a participant recognizes or captures with a fingerstick. 

A recent study found that over half of hypoglycemic episodes are not symptomatic (and would go unrecorded without CGM), highlighting just how beneficial CGM can be to capture these events in clinical trials for new treatments. It is also common for people to sleep through hypoglycemic events or experience hypoglycemia unawareness, meaning they don’t experience symptoms that prompt them to check their blood sugar. Avoiding lows is the No. 1 goal for many people with diabetes and their care teams, so it’s essential to have an accurate, clear picture of hypoglycemia risk before trying a new treatment.

CGM makes participating in trials less of a pain (literally)

Not a fan of fingersticks or waking up in the middle of the night? Just as many people living with diabetes find CGM makes day-to-day management a little easier, CGM can also reduce the time and energy required to participate in a trial and make volunteering to join less daunting. 

“A few points of blood sugar measurements are meaningless compared to every five minutes of glucose information. Why do participants need to poke their fingers unnecessarily when they can use CGM and get all the information on their phone or receiver?” said Shah.

The power of CGM to collect data in the background without disrupting participants’ sleep or daily activities means you can contribute to research without adding to the existing demands of diabetes management. By maintaining usual activities, the trial better captures real-world data; since many factors affect glucose levels, disrupting your routine for trial-related testing could impact results.   

Additionally, applying to participate in a clinical trial can be intimidating, especially when it is hard to understand whether you’re eligible. For example, the currently recruiting ZONE study plans to assess the impact of a new treatment on people with type 1 diabetes “at risk of nocturnal hypoglycemia.” Most people with type 1 have experienced a nighttime low, but what qualifies as “at risk”? The study sponsors make this easier by clarifying that they consider spending more than 1% of the time below 54 mg/dL over four weeks as measured by CGM to be at risk for nocturnal hypoglycemia.

Making sure all people with diabetes are represented

Participating in clinical trials allows people with diabetes to play a part in innovation that could make life better for themselves and the diabetes community down the road. Without people with diabetes participating in trials, none of the research needed to develop new treatments is possible.

Many challenges can make participation difficult for even the most eager participants. For those who don’t live near a study site (often major universities or hospitals) or whose schedules cannot accommodate the frequent visits necessary to participate in most trials, remote data collection using CGM can reduce the need for as many in-person appointments, depending on the study design. 

Studies like the ReDUCe trial are entirely virtual, with participants sharing their CGM data electronically so researchers can measure how telemedicine-delivered cognitive behavioral therapy impacts glucose values and diabetes distress. Collecting glucose data without in-person visits can help investigators recruit more participants who may be commonly left out of trials because of where they live or how much free time they have.

CGM provides consistently accurate data

In addition to making it easier to include more people in clinical trials, CGM helps collect data that accurately represents all participants. While still used as an important metric, A1C levels can vary due to a variety of factors including co-existing conditions, medications, age, and even race. For example, studies have demonstrated that A1C routinely overestimates average blood sugar in Black people with diabetes. 

Using CGM metrics like time in range means researchers can collect reliable, comparable data across all participants, which makes their findings more accurate and useful for all people with diabetes.  

CGM use in trials: The bottom line

The field of diabetes research has come a long way since CGM first came on the scene two decades ago. A1C – the metric historically relied on for trials of all diabetes treatments – provides a limited amount of information. It is ultimately an average over the previous two to three months and does not capture blood sugar highs and lows during that time.

CGM provides the whole picture, helping researchers assess how therapeutic treatments actually affect daily management for people living with diabetes. The growing use of CGM in clinical trials is already changing diabetes research including trial recruitment and assessing treatment efficacy – and will help facilitate the development of even more advanced treatments in the years to come. 

Learn more about CGM use and clinical trials:

• Everything You Should Know About Clinical Trials
• Putting Time in Range at the Forefront of Clinical Trials
• 5 Ways CGM Can Optimize Diabetes Management