Diabetes is a disease that occurs when your blood sugar levels are too high. That blood sugar, known as glucose, is what gives your cells energy. The hormone insulin helps glucose enter your cells.
We spoke with PRA experts Evangeline Costelo, Sr Medical Director—Medical Affairs and Claudia Mano, Sr Medical Director—Medical Affairs about how researchers are addressing diabetes treatment developments and how the healthcare industry might alleviate the diabetes epidemic.
Diabetes can be classified into the following general categories:
- Type 1 diabetes (due to autoimmune β-cell destruction, usually leading to absolute insulin deficiency)
- Type 2 diabetes (due to a progressive loss of adequate β-cell insulin secretion frequently on the background of insulin resistance)
There is no true cure for diabetes, only treatment options. With time, if left untreated, high blood sugar levels damage many organs in your body.
Diabetes is the seventh leading cause of death in the United States, and cases have risen worldwide over the last several decades. In response to this escalating health threat, World Diabetes Day (WDD) was created in 1991 by the International Diabetes Federation (IDF) and the World Health Organization.
In honor of World Diabetes Day, we spoke with Evangeline Costelo, Sr Medical Director, Medical Affairs and Claudia Mano, Sr Medical Director, Medical Affairs about how researchers are addressing diabetes treatment developments and how the healthcare industry might alleviate the diabetes epidemic.
What is your therapeutic experience of diabetes, as well as PRA’s experience in this area?
EC: I joined PRA about a year ago. I'm an endocrinologist by training and practiced for 15 years prior to joining the CRO industry. For endocrinology, the main bulk of our patients are diabetic, and we've been involved in patient consortiums for both type 1 and type 2 diabetes. Patient consortiums allow us to not only treat these patients, but look at other aspects of holistic management as well.
As a previous investigator I worked in more than 30 diabetes clinical studies. At my previous company, I was also involved in diabetes clinical trials ranging from phases I to IV.
CM: I’ve been at PRA for 19 years. I’m also an endocrinologist by training. I have a Master’s degree in thyroid disease and I’ve been in the diabetes therapeutic area for 25 years. Prior to PRA, I worked for over 10 years in the diabetes sector of the Federal University of Sao Paulo in Brazil assisting patients with type 1, type 2, and pregnant women with diabetes.
I’m an expert in type type 1 and type 2 diabetes studies in different phases, as well as in pediatric diabetes studies. At the moment, I’m involved in six diabetes studies—all of them are type 2 diabetes.
How are researchers addressing the challenges around patient recruitment and retention, given that patients may feel they want to stick to a tried-and-tested treatment?
EC: From my experience with diabetes studies, it's not that difficult to recruit patients because there are many diabetes patients available. The challenge is looking at the right patient population and aligning it with a study. Sometimes the protocol may not be aligned with the standard of care.
If the Principal Investigator (PI) is involved with the informed consent process and they’re always present during patient follow-up visits (i.e., re-consenting and giving patients updates), we usually experience less of a challenge for recruitment and retention.
CM: I think this depends on the diabetes type and the population in a given country as well. We have different ways to see those patients and assist them depending on the region. For instance, in Latin America, a patient-physician relationship tends to be more personal, welcoming, and concerning for the individual as a whole. Usually, the patients create a trust relationship with their doctors.
In general, I see barriers for recruitment that we could face in other studies in different indications, such as:
- accommodating work and school schedules
- the number of visits
- lab draws
- site locations, which can be inconvenient for the patient
Patients with type 1 diabetes more often recognize the benefits of clinical trials. But for type 2, sometimes it's not the same. They have obesity and they tend to recognize their obesity as a health issue other than diabetes, mainly because obesity affects their image. We also need to think about pediatric trials. We’ve seen an increase in type 2 pediatric studies, at least in the last four years. Youth onset type 2 diabetes is an emerging disorder in children, adolescents, and young adults and it has particular associated challenges and characteristics.
We are now trying to pursue technology and engage not only the family but also advocacy groups. As Evangeline said, PIs are important because they're the ones that are dealing with the patients on a routine basis. They know the patients well—that definitely helps retention and recruitment.
How do type 1 and type 2 diabetes differ? How often would a patient be seen by their treating physician once they’re on a stable regimen? What's the standard of care for these patients?
EC: Usually, we follow specific clinical practice guidelines. For both types, the recommendation for patients is to be seen by their physician at least once every six months. But that also depends on the on the clinical status of the patient. For both type 1 and type 2 diabetes, there are a lot of things the patient can do on their own, such as home glucose monitoring and laboratory tests.
The challenge, therefore, is that some patients who enter clinical studies have frequent visits. That frequency depends on the phase the studies are in. Sometimes there's a time standard for diabetes trials. During the initial phase, participants may have to come on site every two to four weeks. This time constraint could be a challenge because it would differ from the patient’s routine regular clinic visits, adding an additional burden.
How have diabetes studies changed over the years with the use of wearables and decentralized/remote clinical trials?
CM: In one of my studies, we’re using electronic diaries and alerts that allow us to check the hypoglycemic/hyperglycemic events in real time. Because of COVID, we have to use telemedicine. I’ve seen more and more of our sponsors asking for that in RFPs.
Type 1 diabetic patients are younger than type 2 diabetics, so they're more used to technology. It’s easier for them to add that to their routine. Older, type 2 diabetic patients may not be so tech-savvy, but we can of course help them. For instance, in the past, I worked with paper diaries. Now we're working with electronic diaries. Technology is a logical route for us to go and it increases compliance. It will help us decrease the number of in-person visits.
EC: Before the COVID-19 pandemic began, there was already significant development in decentralized trials. But some pharmaceutical companies were resistant to this idea because of the cost. When COVID-19 arrived, those companies realized it wasn’t just a luxury anymore—it was a necessity. They needed to obtain the data, but they couldn’t do it during the pandemic without technology. COVID-19 has pushed most sponsors to think about adopting more technology-based strategies. Now, patient data will immediately go into a database and the attending physician or investigator will see that alert in real time.Learn more about PRA’s work with decentralized trials.
What stigmas exist around type 1 and type 2 diabetes? Are the stigmas different between the two? How are stigmas for both addressed?
CM: We're better than we were 10 years ago. We have more information now. Still, I believe there are some stigmas that need attention. With type 1, I’ve seen patients who still feel isolated and depressed because they feel they’re a burden to the health system. They might feel like they’re failing in their personal responsibility to take care of their diabetes. I’ve seen patients who say they don’t feel comfortable having their injections at work or in front of their friends.
The public today can still make mistakes differentiating type 1 from type 2 diabetes. The most important thing that people in positions like ours can do to address this is with education and campaigns like WDD, as well as campaigns in hospitals and our communities. At these events, we offer free glucose level checks and spread information about what diabetes is, the difference between the types, and how you can help your colleagues identify it.
EC: Around 5 years ago, the management and treatment of diabetes started to shift from a glucose-centric approach to treating all the aspects of the disease. Treatments moved away from just lowering HbA1c and lowering blood sugar to treating other aspects, such as mental health, cardiovascular, renal complications and empowering patients.
Patient self-care is now a focus of diabetes management. This provides more patient engagement and support. Both type 1 and type 2 have diabetes support clubs.
CM: Like Evangeline said, when a person suffering from a disease sees her colleague or a friend who’s having the same problem, they don't feel so isolated. They have a community where people help each other.
Diabetes can be a huge burden on the patient’s family—we do whatever we can to support them. Imagine if you had a kid, a mother, or a father who needed help with their injections. It’s not always easy to accommodate everything. It’s a change in your family, your routine, and your habits. We need to do what we can to empower our patients—helping them to be part of the treatment and feel like themselves. Their disease doesn’t control their life.
How has the global pandemic affected diabetes patients? How will diabetes patients have to adapt to treatments in the COVID-19 era?
EC: The pandemic is difficult for diabetes patients. This population is at-risk, so it’s recommended that they stay in their house as much as possible. However, there can be some gaps in the follow-up with their physician when the patient is in lockdown. When everyone has to stay inside, diabetes patients get much less physical activity. Their diets can change as well, and all of that can cause a breakdown in their regimen.
With telemedicine, the clinical situation has improved. Patients have a support system available 24/7 that can help them monitor their health during the pandemic.
CM: It has been particularly challenging for diabetic patients because we're now dealing with two huge health situations: the general diabetes epidemic, which is a leading cause of death and a comorbidity with COVID-19, and the COVID-19 virus itself. If you have a preexisting condition like diabetes, you have a strong chance of contracting a more severe form of COVID-19.
In clinical trials, we’ve used telemedicine to keep the trials running smoothly. We had to adapt our protocols to using more telemedicine since we had to follow guidelines to isolate. We’re trying our best to accommodate all of these changes. Clinical trials involve multiple locations and not all the locations have online access.
We’ve accepted subjects to download data from electronic diaries. We help the sites create solutions in case patients do not have internet available, such as telephone visits. Working together with sites to create solutions based on their capabilities has been critical and eye-opening.
Diabetes disproportionately affects racial/ethnic minority populations. Compared with Caucasian adults, the risk of having a diabetes diagnosis is 77% higher among African Americans, 66% higher among Latinos/Hispanics, and 18% higher among Asian Americans. How can we better ensure representation of people who need diabetes drugs most?
EC: There are many factors to consider here, such as the practice location and insurance coverage. It strongly depends on the country’s healthcare system and its citizens’ socioeconomic status.
I don’t believe that any physician will discriminate any patient. But there are so many factors to consider when we are treating any patient. Two of these factors are practice location and insurance coverage.
CM: Unfortunately, minorities are always disproportionately affected because these systems are inherently disproportionate. Sometimes they don't even have access to healthcare. In Brazil, we have many people with diabetes who don't have access to the public healthcare system.
I believe that we need involve our governments in these issues by spreading awareness and campaigns. I don’t think any physician wants to decline assistance to the patient outright, but sometimes they have to because of the limitations from the healthcare system.
Depending on the country, we see some regions where the healthcare is more developed and other regions where healthcare access is not available. We need to work to improve this discrepancy by involving public policies and incentives to make physicians and specialists available in those regions.
Diabetes is set to become an even larger healthcare challenge than it is currently, with incidence rising. How will the healthcare industry come together to alleviate that?
EC: I’d say the rising cases of diabetes have been a challenge for the past 20 years or more. For the healthcare industry, we’re looking at newer, more affordable therapies. However, there are still many countries, like where I live in The Philippines, where the patient pays out-of-pocket for treatment and general healthcare. The healthcare industry is looking for solutions to decrease the cost for people to receive general healthcare, as well as making it more accessible to everyone.
CM: Not everyone has access to the “best” treatments, such as “better” insulin. Not everyone can afford the best standard of care. Not everyone has access to healthy food. They may have limitations as to how they can exercise. If we can work around this with our healthcare system and communities, that will be groundbreaking.
Finally, we need intervene with patients who are pre-diabetic. This is a huge population and we need to find more ways to reach them before it’s too late. If we use the same language to help the patients be compliant, we can also avoid the chronic complications that are a burden to the healthcare system. This involves changing a lot of things on the personal level, such as individual habits and routines.
Our in-house therapeutic experts leverage their existing relationships with leading investigators and key opinion leaders in cardio-metabolic diseases to effectively execute patient recruitment and site management and support strategies.
We’ve conducted studies with at least 30 compounds developed for the treatment of type 1 or type 2 diabetes or metabolic syndrome, and the majority of our Phase I and II studies were performed in our clinical pharmacology units in the Netherlands and the US.
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