Lindus Health launches OPHTHALMOLOGY CRO offering.
READ MORE
This blog was co-written in collaboration with Dr. Carel Le Roux, clinician scientist. Carel recently supported the SURMOUNT-2 clinical trial which assessed tirzepatide on weight reduction maintenance in adults with obesity and type 2 diabetes. Dr. Le Roux is an advisor to Lindus Health and he serves as the Director of the Metabolic Medicine Group at University College Dublin. He also holds Professorial positions at Ulster University and the University of Pretoria.
GLP-1 medications have proven to be highly successful in the treatment of type 2 diabetes and obesity, demonstrating benefits in glycemic control, weight loss, cardiovascular risk factors, and quality of life. These drugs, including semaglutide and tirzepatide have skyrocketed in popularity over the last year. By the end of 2024, GLP-1s are projected to become the best-selling drug class of 2024, bringing in $50 billion in revenue this year alone.
Despite the marked success of GLP-1s in diabetes and obesity management, primary care physicians (PCPs) have shown reluctance to incorporate these medications into their patients’ treatment plans. In addition to challenges related to permissions for reimbursement and medication availability, there is a significant gap in testing obesity drugs in the settings where they will actually be used, contributing to their widespread lack of adoption within primary care. Research also suggests there are racial, ethnic and socioeconomic inequities in GLP-1 use. To further promote acceptance of GLP-1s, pharmaceutical companies must work directly with primary care facilities to run their clinical trials to exhibit their efficacy in real-world settings and among various ethnic populations.
GLP-1 based drugs, or partial/specific glucagon-like peptide-1 receptor analogues, are a class of medications primarily used to treat type 2 diabetes and obesity. These drugs mimic the action of hormones such as GLP-1, which plays a crucial role in regulating blood sugar levels and appetite. They are mainly available in the form of an injection to be administered once daily or weekly, however oral formulation are available on the market today, and more are in the pipeline.
GLP-1 based drugs have demonstrated significant improvements in patient outcomes for those with diabetes and obesity through various mechanisms and benefits.
Like any prescription medication, GLP-1s have their share of potential adverse effects, but most of these are not only predictable but can easily be managed because the side effects are usually mild to moderate and often subside with time. The side effects include:
Clinical trials for GLP-1 medications have predominantly taken place in hospital settings, where study activities and other variables are highly standardized and tightly managed. Here, researchers and participants benefit from the advanced expertise of hospital specialists, research nurses, dietitians, and other healthcare professionals who can perform comprehensive assessments and closely monitor the effects of an investigational product.
GLP-1 based medications have displayed excellent efficacy in the management of diabetes and obesity in these settings, however this does not automatically lend to their adoption in primary care. Although PCPs treat approximately 90% of diabetes patients in the US, they remain apprehensive as a whole in prescribing GLP-1s for long-term use.
Many PCPs may be hesitant to prescribe GLP-1 agents due to lack of experience with these medications. These interventions are still relatively new compared to existing diabetes drugs, so there is still skepticism on whether or not these drugs’ mechanisms and side effects are well enough understood.
Because GLP-1 based medications are mainly available as injections, doctors may perceive difficulty with self-administration, especially for older individuals. After all, there are several classes of diabetes medications available in oral formulations that are effective.
Administrative concerns such as cost and coverage persist, as not all insurance companies or public payers cover GLP-1s for both diabetes, obesity, or even at all. For patients whose insurance does cover these medications, they still may have to go through the red tape of seeking prior authorization approval or have high co-pays.
The adoption of GLP-1 medications for both obesity and diabetes needs to consider not just the workload for prior authorizations, but also the new workload associated with commencing, titrating and monitoring of these drugs. This is especially true for obesity patients as PCPs usually currently have limited involvement in the management of obesity, so this new pathway could significantly impact the workloads for doctors.
Concerns over the use of GLP-1 therapies among primary care professionals underscore the need for more comprehensive research of these drugs in this setting. Designing a clinical trial for the evaluation of GLP-1s in primary care involves collaboration with practices with the infrastructure to conduct clinical trials that both capture all the necessary data to meet study endpoints and promote patient-centricity.
Employing primary care facilities as clinical trial sites allows for the evaluation of GLP-1 medications in the setting they will be most often used. Most contract research organizations (CROs) have networks of primary care practices they already work and have relationships with, making them valuable sources in identifying potential sites with clinicians who have experience with GLP-1s and adequate patient populations. Ensuring diversity for these trials is also an important variable in primary care adoption of GLP-1 therapies, so it is crucial to vet sites for their patient populations, assessing demographics including race, ethnicity, and socioeconomic status.
There are several important factors to consider when deciding between a remote, hybrid or traditional site model to study GLP-1s in this setting. Traditional models will likely recruit more sites, as PCPs will then be able to directly observe the effects of the medication and provide care to participants. A fully remote model, however, is not entirely out of the question, as blood draws can be performed through self-collection technologies and mobile phlebotomists and/or research nurses.
To reduce the patient burden of frequent travel to doctors’ offices, it is beneficial to utilize methods to collect trial data outside of study visits. Depending on the GLP-1 indication, various technologies can be utilized to collect biological markers and even integrated within other platforms to automatically send data for medical review. For example, trials for diabetes management can assess blood sugar levels via continuous blood glucose monitors. Studies assessing cardiovascular outcomes may provide participants with blood pressure for self-use, AppleWatches, wearable ECG monitors, and more.
In addition, qualitative data pertaining to side effects, experience with the investigational product and trial, adherence, and quality of life measures can be collected through ePRO questionnaires on a regular cadence. This gives patients the opportunity to provide subjective insights on their experience while enhancing patient engagement and providing study teams with feedback for potential improvement.
PCPs are typically the point of contact for many within the healthcare system and they are best placed to know their patients’ health histories, comorbidities, and lifestyles. As a result of their long-standing relationships built on trust, they can be strong motivators in encouraging their patients to engage in clinical research. Patients will likely be more amenable to joining GLP-1 studies knowing their doctor or a physician at their doctor’s practice is the PI, as they would not have to travel to another center to receive care throughout the study and may even be able to combine study visits with regular visits.
To identify candidates for participation, CROs with access to a network of primary care facilities can run coded searches according to GLP-1 studies’ eligibility criteria, screening for patients who fall within a certain BMI, metabolic range, diagnosis, and more. This will ultimately reduce the rate of screen failures and accelerate enrollment timelines. To take it a step further, CROs can also disseminate invitations to join a study through a facility’s communication system (i.e. text messages directly from a doctor’s office) to further enhance trust.
GLP-1 clinical trials are often lengthy in duration as it can take several months to see significant effects of the medication. Those observing long-term health outcomes may even last several years. Therefore, it’s important to implement a comprehensive patient engagement strategy to collect sufficient data to meet endpoints and keep patients from dropping out of a study.
ePRO questionnaires are great for both collecting qualitative data and promoting engagement with the study. Personalized reminders from the study team, sent via text or messaging apps, enhance adherence to study protocols by prompting patients to use the investigational product, complete ePRO questionnaires, and attend study visits on time, tailored to individual schedules for easier participation. Additionally, incentivizing patients for attending study visits and the completion of even small study activities, such as ePRO, encourages patients to complete study activities on time. For example, consider implementing a payment schedule where small payments of $5-10 are given per each day a questionnaire is completed on time.
GLP-1 medications have emerged as important therapies in the management of type 2 diabetes and obesity, offering substantial benefits in glycemic control, weight loss, and cardiovascular health. Despite their proven efficacy and increasing popularity, there remains a significant gap in their adoption within primary care settings. Addressing this gap requires concerted efforts to integrate GLP-1 trials into primary care environments, demonstrating their effectiveness in real-world conditions. Partnering with primary care facilities and leveraging modern data collection, recruitment, and engagement strategies aims to enhance the accessibility and utilization of these novel therapies to improve patient outcomes on a broader scale.
