Managing Side Effects and Dosing in Off-Label GLP-1 Use with Help from Real-World Evidence

In an interview with Applied Clinical Trials, Shipra Patel, global therapeutic area section head for endocrinology and global head of pediatrics at Parexel, discussed the evolving landscape of obesity drug development and what it takes to stand out in a field crowded with more than 90 active sponsors. Patel emphasized the importance of therapeutic depth, cross-functional collaboration, and the strategic use of real-world evidence to design safer, more effective clinical trials—particularly as GLP-1 therapies expand into new indications such as Alzheimer’s, addiction, and MASH. She also shared how Parexel is adapting its clinical infrastructure to meet the growing complexity of this space, while keeping long-term patient engagement and global data integrity at the forefront.

ACT: Off-label use of GLP-1s is rising, even among individuals with normal BMI. What unique safety considerations must trial sponsors keep in mind, and how does real-world evidence help address those concerns?

Patel: Real-world evidence has shown that many people don’t stay on GLP-1s for long. One reason may be cost—insurance coverage isn’t always sufficient. Tolerability is another factor, particularly gastrointestinal side effects, which can limit long-term use.

Another key insight is that dosing can be more flexible than in traditional clinical trials, where there's often a push to escalate quickly. In practice, we’ve seen that even submaximal doses can provide meaningful health benefits—not just for weight loss, but also for metabolic improvements.

These real-world insights help inform trial design by highlighting factors like adherence, dosing flexibility, and side effect management. They allow us to better anticipate and address patient needs in both research and clinical settings.

Full Interview Summary: With more than 90 sponsors now driving obesity drug trials, standing out in this competitive space requires deep therapeutic expertise and cross-functional coordination. According to leaders at Parexel, the key differentiator for a standout research partner lies in a nuanced understanding of the evolving obesity drug market—particularly GLP-1 therapies. These compounds, initially developed for diabetes and obesity, are now being investigated for a broad range of indications including MASH, Alzheimer’s, addiction, Parkinson’s, and sleep apnea. To support this complexity, Parexel has implemented a GLP-1 task force—an internal expert group that helps clients stay competitive across the drug development lifecycle.

To handle GLP-1 trials spanning multiple therapeutic areas, Parexel relies on a therapeutically aligned model, connecting area leads across endocrinology, cardiology, psychiatry, and pulmonology. These cross-disciplinary teams collaborate to translate clinical trial learnings between indications and optimize study designs for similar mechanisms of action.

Real-world evidence (RWE) plays a central role in addressing the safety concerns linked to rising off-label GLP-1 use, even among patients with normal BMI. RWE shows many patients discontinue treatment early, often due to costs or tolerability issues—particularly gastrointestinal side effects. Flexible dosing, even below the maximum level, may still yield metabolic benefits, offering a new lens for trial design.

Parexel has leveraged RWE to identify non-traditional patient populations and refine trial protocols—for instance, by pinpointing regions with high use of GLP-1s to aid recruitment for switch-over studies. Looking ahead to 2050, long-term patient retention, better compliance tracking, and global data accuracy will be essential to compare therapies and identify long-term leaders in the obesity space. Innovations in AI and global patient engagement will be critical in sustaining participation and capturing meaningful safety outcomes.