Measuring what the scale can’t: Understanding the risks of lean tissue loss with GLP-1

The most important number in medical weight loss isn’t necessarily the number on the scale.

New therapies are helping patients achieve substantial weight loss once rarely seen outside of surgery. Large clinical trials report average weight reductions of approximately 15% with semaglutide, and up to about 21% with tirzepatide in some populations.^{1 2}

That progress is meaningful. But weight loss alone does not indicate what was lost. 
Research evaluating body composition during GLP-1–associated weight reduction shows that weight loss may include reductions of approximately 30% of body weight lost with GLP-1Ra-based therapy as lean mass.³

BMI was never designed for this moment

BMI has long served as a simple assessment tool. It does not directly measure body fat or distinguish between fat, muscle, and bone.⁴ Two individuals with the same BMI can have very different metabolic risk profiles. 

In the GLP-1 era, that limitation is more visible, as skeletal muscle is intricately involved in locomotion and mobility and can play a role in metabolic health.⁵ Significant or rapid weight loss can include reductions in lean tissue that could have undesirable outcomes.³

DXA as a clinical reference standard

Dual-energy X-ray absorptiometry (DXA) is widely used as a reference method to assess body composition, including fat mass, lean mass, and bone mineral content.

Cardiometabolic risk is strongly associated with visceral adipose tissue .⁶ With 43% of adults globally classified as overweight in 2022.⁷

A more informed conversation around lean mass

Weight reduction, particularly when rapid, can include some degree of lean tissue loss.³

When lean mass declines, it can affect metabolic rate and physical function and is often associated with fatigue and reduced activity levels. Over time, these changes can make it more difficult to maintain weight loss.³

For older adults, maintaining lean mass is associated with strength and functional independence. Resistance training and adequate protein intake are recommended to help maintain muscle with aging.⁹

The clinical question is evolving: not just “How much weight?” but “What changed?”

Body composition for sports medicine

Body composition assessment is used in sports medicine and orthopedic settings to evaluate lean tissue balance to help clinicians asses physical adaptation.

Muscle imbalances have been identified as a potential risk factor for injury in athletes.¹⁰ Quantitative assessment can support injury rehabilitation planning and return-to-play decisions.

Preserving lean mass during weight loss is important for maintaining physical function, independence, and metabolic health.¹¹

Why health systems are expanding body composition services

Market analysts estimate that the number of individuals using GLP-1 therapies in the United States may increase substantially in the coming years.¹²

DXA enables assessment of body composition and tracking of changes over time, supporting  monitoring and metabolic risk evaluation. GE HealthCare’s DXA portfolio, including Lunar iDXA and Prodigy systems, provides body composition analysis alongside bone health assessment.

DXA services are commercially available in the United States, with multiple providers offering body composition assessment for longitudinal tracking.

The scale shows change. Body composition helps explain what changed.

Footnotes:

1. Wilding JPH et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (2021) https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

2. Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity (2022) https://www.nejm.org/doi/full/10.1056/NEJMoa2206038

3. What happens when you lose muscle? Cleveland Clinic Research on risks, predictors and prevention What happens when you lose muscle Cleveland Clinic Research on risks predictors and prevention

4. Centers for Disease Control and Prevention (CDC). BMI Frequently Asked Questions https://www.cdc.gov/bmi/faq/

5. Frontiers. Inter-set stretch: A potential time-efficient strategy for enhancing skeletal muscle adaptations (2022) www.frontiersin.org/journals/sports-and-active-living/articles/10.3389/fspor.2022.1035190/full

6. Estimated visceral adiposity is associated with risk of cardiometabolic conditions in a population based study (2021) https://www.nature.com/articles/s41598-021-88587-9?

7. World Health Organization (WHO). Obesity and Overweight (2022) https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

8. Cleveland Clinic. What happens when you lose muscle? (2025) www.lerner.ccf.org/news/article/?title=What+happens+when+you+lose+muscle

9. Dodds RM et al. Sarcopenia and Healthy Ageing (2019) https://academic.oup.com/ageing/article/48/1/16/5126243

10. National Library of Medicine. Balancing Act: Muscle Imbalance Effects on Musculoskeletal Injuries (2022)
https://pmc.ncbi.nlm.nih.gov/articles/PMC9324710/

11. MDPI. Weight Loss Strategies and the Risk of Skeletal Muscle Mass Loss www.mdpi.com/2072-6643/13/7/2473

12. J.P. Morgan. Obesity Drugs: Market Insights (2023) https://www.jpmorgan.com/insights/global-research/current-events/obesity-drugs