Measure body composition: A potential proxy for higher-quality weight loss

This is section 2 of Parexel's "Navigating to 2030" playbook series on differentiating next-generation obesity therapies. This series offers strategic insights across trial design, regulatory considerations, clinical operations, and patient retention strategies to support sponsors in this rapidly evolving and competitive market.  To navigate to other sections, click the buttons below.

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Products that reduce fat mass (FM), maintain or increase lean body mass (LBM), and preserve bone mineral density (BMD) could have a meaningful competitive edge if they are perceived as delivering higher-quality weight loss. Obesity drug sponsors increasingly come to us with the same questions: When should we start collecting body composition data — Phase 1 or Phase 2? What is the minimum trial duration to capture meaningful changes? Which measurement tools and imaging modalities work best? And how do we demonstrate that better body composition in a trial translates into functional benefits in the real world?

Championing the clinical value of preserving lean mass

High-quality weight loss requires reducing FM, particularly visceral fat, while actively preserving, or increasing LBM. LBM preservation is associated with improved metabolic function, greater physical capacity, and reduced frailty. The argument is especially compelling for older patients susceptible to sarcopenia, where losing additional LBM to pharmacotherapy is counterproductive to functional independence — and for MASH patients, where improving body composition often translates directly into metabolic health.

Sponsors who intend to make label claims about body composition must align with regulators on endpoints. And to convince payers, they must champion the clinical value of preserving lean mass, backed by data.

Body composition measurement strategies

A recent Parexel review of obesity trials registered on clinicaltrials.gov found that studies increasingly use multiple complementary measures of body composition.¹ FM is a primary endpoint in 28% of recent trials; LBM in 21%; and BMD in 7% (n=124). No single assessment method is fully accurate, but two are most common:

• Dual-energy X-ray absorptiometry (DXA), used in 35% of trials, provides a practical and reliable measure of total body composition and BMD. Standardization is good, but cost and logistics at scale remain challenges. In a recent Phase 1 study, technicians were unable to complete DXA scans for several patients due to their physiques, and had to repeat others because of improper positioning. This slowed randomization until we mitigated the problem with site training and advance preparation.
• Bioelectrical impedance analysis (BIA), used in 36% of trials, is highly accessible and low-cost. But even medical-grade BIA scales are less accurate than site-based methods and depend heavily on hydration status; patients must avoid alcohol and caffeine for 24 to 48 hours before a test.

Computed tomography (CT) and magnetic resonance imaging (MRI) are the gold standards because they produce high-resolution, cross-sectional images that distinguish fat mass, lean mass, and muscle quality — but both are costly, MRI scanners are less widely available than DXA, CT exposes patients to ionizing radiation, and MRI has weight limits. We typically recommend BIA in conjunction with DXA scans as a secondary or exploratory endpoint; these are also the easiest tools for patients to access in clinical practice and will likely carry the load for real-world evidence once drugs are on the market.

The case for MRI in early-phase studies

MRI offers more precise fat distribution analysis and a wider array of lean tissue and muscle volume endpoints. An increasing number of Parexel’s sponsors are incorporating MRI into Phase 1 trials. In one recent case, MRI was reinstated into a Phase 1 protocol because the preliminary body composition data was needed to guide endpoint design for later pivotal trials.

When MRI is incorporated early, operational planning must follow. Scanners are not always available; performing MRI scans on obese patients requires additional training for vendors and site staff, and central reviewers must review participants’ MRI data before randomization. In a recent early-phase obesity study, we used specialized MRI-based assessments of liver fat and body composition. Capturing these data required sites to have MRI scanners from major manufacturers, equipped with a specific software package and calibrated for accuracy. Incidental findings required principal investigators to follow up with referrals. Incorporating endpoints beyond weight loss requires site qualification, imaging standardization, and operational planning to ensure consistency. Sponsors must plan for these realities.

Linking body composition to functional outcomes

Body composition data only carries regulatory and commercial weight when tied to functional benefit. Sponsors should pair imaging endpoints with performance-based tests that demonstrate sustained or improved muscle function. The most clinically useful in our experience are the short physical performance battery (SPPB), the sit-to-stand test, and hand grip strength measured with handheld dynamometry. The six-minute walk test (6MWT) captures endurance but takes longer to administer. The stair climb power test is particularly relevant for older patients, where loss of stair-climbing capacity signals compromised independence.² 

Objective performance data should be layered with subjective patient experience. Is a good 6MWT score actually meaningful to patients? Patient-reported outcomes give clinical endpoints their commercial meaning — particularly when the payer question is whether better body composition translates to a better life.

Securing long-term value with quality outcomes

Sponsors who measure body composition accurately, validate the functional benefits, and link them to outcomes patients value will protect their compounds against competing therapies — and capture not just the magnitude of weight loss, but its quality.

Resources

1. Parexel review of obesity trials planned, ongoing, or completed as of 2025 (unpublished data). Queried clinicaltrials.gov for 2025 trials containing key search terms (including “obesity,” “overweight,” “bariatric surgery,” and “body composition”) and identified 124 clinical trials.
2. The Stair Climb Power Test as an Efficacy Outcome in Randomized Trials of Function Promoting Therapies in Older Men, The Journals of Gerontology: Series A (July 6, 2019).

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