Unlocking Obesity CRO Insight: The Role Imaging Plays in the New Era of Obesity Drug Development

Introduction

Globally, the prevalence of obesity is experiencing significant growth, with the impact and burden this places on global healthcare reaching remarkable levels. Rising rates of obesity are driving an increase in the incidence of diabetes, cardiovascular disease, hypertension, stroke, and a whole range of other metabolic disorders.

Given this backdrop, the global research community has been intensifying efforts to better understand the complex biology of obesity in an attempt to develop more effective, targeted, and sustainable therapeutic solutions. Results of this ongoing research have brought about a growing recognition of obesity as a multi-factorial metabolic disorder, involving the interplay of genetics, cellular function, and fat-cell signaling for example, rather than purely a consequence of lifestyle or specific health behaviors, shifting the way in which obesity trials are being designed and managed.

How Perceptive Imaging is helping sponsors to design smarter obesity trials

As an obesity CRO, we draw on our extensive experience in musculoskeletal and obesity clinical trials to enhance success in this field, driven by a team with a deep understanding of the landscape of obesity research. One such team member is Dr. Farhan Syed, who has 20+ years of musculoskeletal biology, metabolic disease, and body composition research experience and expertise in imaging-based assessment of muscle and fat distribution. He has been involved in the conduct and interpretation of imaging in numerous obesity studies, helping sponsors better understand the imaging biomarkers most appropriate to ascertain effects of emerging and innovative therapies in this area.

Q: How would you characterize the current global landscape of obesity research and drug development?

FS: We are seeing an unprecedented push to identify new drug candidates and mechanisms of action, based on a recent, broader appreciation that obesity is a complex, multifactorial disease tied to comorbidities such as cardiovascular disease, diabetes, and even respiratory conditions like COPD.

In addition to today’s wide-ranging research on GLP-1 and GIP receptor agonist, we’re seeing increased interest in obesity as an inflammatory and metabolic disorder, with research exploring how fat distribution, tissue function, and inflammation contribute to overall disease burden. 

With over 500 worldwide obesity trials active today and more candidates in play, differentiation will increasingly come down to mechanism of action, imaging biomarkers, and clinical outcomes.

Q: How has the recognition of obesity as a chronic metabolic disease changed the way trials are designed?

FS: Historically, obesity studies focused almost exclusively on weight loss as the primary endpoint. Today, however, there’s a growing interest toward understanding how weight is lost and the impact this has on organ systems. Researchers are beginning to monitor the molecular and cellular pathways of fat tissue, visceral fat changes, adipose tissue, organ health, and metabolic outcomes alongside traditional measures like BMI and circumference.

Modern-day obesity clinical trials increasingly rely on discriminatory imaging, including secondary imaging endpoints to assess muscle, liver, and fat composition, providing a more holistic picture of therapeutic benefit and safety.

Q: What imaging modalities are most relevant for obesity trials?

FS: The mainstay remains DEXA (Dual-Energy X-ray Absorptiometry), which is well validated and provides precise data on changes in lean and fat mass. It’s excellent for distinguishing subcutaneous from visceral fat and is widely available across sites.

MRI is gaining prominence for its ability to measure fat deposition in organs like the liver and kidneys, offering insights that DEXA cannot capture. CT scans are sometimes used to assess abdominal adipose tissue, and echocardiography may be incorporated depending on the endpoints under investigation.

At early research stages, advanced imaging modalities such as FAPI-PET are being explored to establish mechanisms of action and to confirm that a drug is acting on its intended biological target.

Q: What are the biggest scientific and operational challenges sponsors face in developing obesity therapies?

FS: Scientifically, the main challenge is aligning study design with the mechanism of action of the candidate. Sponsors must ask: What comorbidities are being targeted? What endpoints make sense? How much change is expected, and how do we statistically power the study to detect that?

Obesity is a heterogeneous condition, which makes endpoint selection complex. Imaging helps us to answer critical questions: Are we preserving lean mass while reducing fat mass? Are we targeting subcutaneous, visceral, or ectopic fat? These nuances matter for both efficacy and safety and need to be considered from the outset.

Operationally, the FDA’s draft guidance recommends demonstrating fat reduction while preserving lean mass but leaves imaging modalities flexible. Sponsors must balance this with logistical factors, such as multi-center trials, equipment compatibility, software requirements, and ensuring scanners can accommodate high-BMI participants. These considerations can have significant cost and scheduling implications.

Q: How does Perceptive support sponsors in overcoming these challenges?

FS: Communication is critical. From the very start, we engage closely with sponsors to align on endpoints, imaging methods, and site readiness. We provide image acquisition guidelines, conduct site training, and work collaboratively with CROs and imaging teams to ensure high-quality, reproducible data.

We have extensive experience in musculoskeletal and obesity trials, with multiple studies currently underway. Our teams work closely with sites and sponsors to standardize imaging parameters, conduct pre-study training, and deliver ongoing quality checks.

Our goal is to create efficiencies and proactively address potential issues, from scanner compatibility to data quality, before they impact the trial. At Perceptive, we see ourselves as partners, working side by side with our clients to optimize imaging strategies, interpret complex data, and accelerate the development of next-generation obesity treatments.

Q: If you could offer one piece of advice to sponsors developing obesity therapeutics, what would it be?

FS: Don’t underestimate the logistical and technical aspects of imaging. Consider early on how many participants can realistically be imaged, what quality of data you’ll achieve, and how those outputs align with your primary and secondary endpoints. Imaging is powerful, but only when planned and integrated properly into the study design. 

Obesity innovation is a rapidly evolving field of study, and imaging will continue to play a central role as modalities advance and AI-driven analysis expands.