Quick Answer: What Is the Muscle Question Behind Tirzepatide Weight Loss?
The modern weight-loss question is no longer only “How much weight was lost?” but also “What was lost?”
Tirzepatide produces substantial reductions in body weight, with fat mass generally accounting for the majority of the reduction. However, lean mass also decreases during significant weight loss.
A 2026 systematic review and meta-analysis of 20 randomized controlled trials involving 15,782 participants found that lean mass represented approximately 25.4% of total weight lost with tirzepatide. Across incretin therapies overall, the proportion ranged from approximately 25% to 39%.
The same analysis found that lifestyle interventions combined with resistance training had the most favorable profile, with lean mass accounting for approximately 17.5% of total weight lost.
This does not mean that tirzepatide “causes muscle wasting,” nor does it mean that 25.4% of weight lost is necessarily skeletal muscle.
Lean mass measurements can include multiple non-fat tissues, fluids and organs, depending on the measurement technique.
For healthy aging, the more useful question is therefore:
Key Takeaways
- Tirzepatide reduces fat mass substantially, but lean mass also declines during major weight loss.
- A 2026 meta-analysis found that approximately 25.4% of weight lost with tirzepatide was lean mass.
- Across incretin therapies, lean mass represented approximately 25%–39% of total weight lost in the 2026 analysis.
- Lean mass is not synonymous with skeletal muscle; DXA lean mass should not automatically be described as “muscle loss.”
- The SURMOUNT-1 DXA substudy found approximately 74% of tirzepatide-associated weight loss was fat mass and approximately 26% was lean mass.
- Resistance training has a favorable evidence profile for preserving fat-free mass during weight loss.
- A 2026 meta-analysis found lifestyle interventions plus resistance training had the most favorable lean-mass proportion among the compared strategies.
- Adequate protein intake is another important component of a muscle-preservation strategy, particularly when appetite and total energy intake are reduced.
- Protein and resistance training are complementary rather than interchangeable: protein provides substrate, while resistance exercise provides a mechanical stimulus for muscle adaptation.
- Healthy aging makes muscle preservation especially important because muscle mass, strength and physical function contribute to resilience and independence.
- Body composition should be interpreted together with strength and function rather than relying on scale weight alone.
- The injection pen is a delivery format; it does not itself determine whether lean mass is preserved.
Introduction: The Number on the Scale Does Not Tell the Whole Story
Modern obesity treatment has changed the scale of achievable weight loss.
Tirzepatide can produce substantial reductions in body weight in people with overweight or obesity.
But as weight-loss treatments become more effective, another question becomes increasingly important:
What happens to the body’s lean tissue while fat is being lost?
This question matters because not all kilograms have the same biological meaning.
Reducing excess adipose tissue can improve metabolic health.
Preserving muscle and other lean tissues can support physical function, strength, mobility and healthy aging.
These goals are not necessarily contradictory.
In fact, the most sophisticated approach to modern weight management increasingly focuses on body-composition quality rather than weight reduction alone.
What Does “Lean Mass” Actually Mean?
This is the first distinction that needs to be made.
Lean mass is not the same thing as skeletal muscle.
Depending on the measurement technique, lean or fat-free compartments can include skeletal muscle as well as other non-fat tissues and components.
DXA, bioelectrical impedance analysis, MRI and CT do not measure exactly the same biological compartment.
| Term | What It Means | Why It Matters |
|---|---|---|
| Fat mass | Body fat measured by a body-composition method | Primary target of adiposity reduction |
| Lean mass | Non-fat tissue compartment defined by the measurement method | Useful for tracking overall body-composition change |
| Fat-free mass | All body components other than fat, depending on methodology | Often used in weight-loss research |
| Skeletal muscle mass | Muscle tissue responsible for force production and movement | Central to strength, mobility and healthy aging |
| Muscle function | Strength, performance and functional capacity | May be more clinically meaningful than mass alone |
This distinction is essential when interpreting the phrase “muscle loss” in weight-loss research.
A reduction in DXA-derived lean mass should not automatically be interpreted as an equivalent percentage reduction in skeletal muscle tissue.
What Did the SURMOUNT-1 DXA Study Show?
A body-composition substudy of SURMOUNT-1 examined 160 participants using dual-energy X-ray absorptiometry.
The participants had baseline and Week 72 DXA measurements.
With pooled tirzepatide treatment, researchers observed:
- −21.3% body weight;
- −33.9% fat mass;
- −10.9% lean mass.
Approximately 75% of the weight lost was fat mass and 25% was lean mass.
The authors reported that this proportion remained broadly consistent across several subgroups, including sex, age and magnitude of weight reduction.
This is an important result, but it should be interpreted carefully.
The study does not mean that one quarter of the body’s skeletal muscle disappeared.
It means that, using the DXA body-composition definitions in that study, approximately one quarter of the total weight reduction was categorized as lean mass.
The 2026 Meta-Analysis Makes the Muscle Question More Interesting
The newer 2026 systematic review and meta-analysis examined 20 randomized controlled trials and 15,782 participants.
It compared incretin-based pharmacotherapy with lifestyle interventions and evaluated the proportion of weight loss attributable to lean mass.
The pooled estimates were:
| Intervention | Lean Mass as % of Total Weight Loss |
|---|---|
| Semaglutide | 35.2% (95% CI 31.5–38.9) |
| Tirzepatide | 25.4% (95% CI 22.8–28.0) |
| Liraglutide | 26.8% (95% CI 23.1–30.5) |
| Lifestyle intervention | 26.2% (95% CI 24.1–28.3) |
| Lifestyle + resistance training | 17.5% (95% CI 14.2–20.8) |
The researchers concluded that lean-mass loss during substantial weight reduction is meaningful across treatment modalities, while integrating resistance training, adequate protein intake and body-composition monitoring may improve muscle preservation.
Does This Mean Tirzepatide Is Bad for Muscle?
No.
That conclusion would be too simplistic.
The correct interpretation is that large-scale weight loss tends to reduce both fat mass and lean mass, regardless of whether the weight loss is achieved pharmacologically or through lifestyle intervention.
The key question is therefore not whether any lean mass changes occur.
The better question is:
Current evidence suggests that the answer may be yes, particularly when weight-loss treatment is combined with resistance exercise and adequate nutritional support.
Why Resistance Training Changes the Equation
Weight loss creates a biological environment in which stored energy is being mobilized.
Without an appropriate mechanical stimulus, some lean tissue can be lost alongside fat.
Resistance training introduces a different signal.
It challenges muscle to produce force against external resistance.
That mechanical stimulus can support the maintenance of muscle tissue and strength during periods of energy restriction.
A 2025 systematic review and meta-analysis of 25 randomized controlled trials found that adding resistance exercise to dietary weight loss:
- protected against loss of fat-free mass;
- increased fat-mass loss;
- and improved muscular strength.
The effect on fat-free mass had moderate certainty, while the evidence for greater fat loss was high certainty.
Resistance Training Does Not Have to Increase Scale Weight to Be Successful
This is an important concept for people using anti-obesity therapies.
Someone may see slower changes on the scale while simultaneously improving body composition.
Why?
Because scale weight is the sum of multiple compartments.
A person can lose fat while maintaining more lean tissue.
Therefore, a smaller numerical change on the scale does not automatically mean that the treatment is less successful.
For body composition, the quality of the change can matter.
Resistance Training and Healthy Aging
This becomes especially relevant in Da Lat.
Da Lat attracts long-stay residents who may be interested in a slower lifestyle, outdoor activity and healthy aging.
For this population, the goal of weight management may not simply be to become lighter.
It may be to become:
- metabolically healthier;
- physically capable;
- strong enough for daily activity;
- resilient enough to remain independent;
- and able to maintain physical capacity as the years pass.
That changes the meaning of “successful weight loss.”
For an older adult, losing excess adiposity while preserving strength and physical function may be substantially more meaningful than achieving the lowest possible scale weight.
Muscle Mass Is Only Part of the Healthy-Aging Equation
Muscle preservation is important, but healthy aging is not determined by muscle mass alone.
Functional capacity also matters.
Two people can have similar lean-mass measurements but very different physical capabilities.
Relevant domains include:
- strength;
- balance;
- walking capacity;
- ability to rise from a chair;
- ability to climb stairs;
- exercise tolerance;
- and independence in daily activities.
For this reason, recent clinical guidance recommends that muscle strength and function be assessed alongside nutritional and body-composition considerations during obesity treatment.
The Protein Question
Resistance training provides a mechanical stimulus.
Protein provides amino acids needed for tissue maintenance and remodeling.
During significant weight loss, reduced appetite can make adequate protein intake more difficult.
This is especially relevant with therapies that substantially reduce appetite and spontaneous energy intake.
Recent clinical guidance therefore emphasizes optimizing protein intake alongside resistance training as part of a lean-mass preservation strategy. The 2026 ADA Standards of Care notes evidence supporting protein intake above approximately 1.3 g/kg/day for maintaining muscle mass during weight reduction, while also emphasizing that increased protein may have greater relevance when combined with resistance training.
However, protein targets should not be interpreted as a universal prescription for every individual.
Age, body size, kidney function, medical conditions, total energy intake, dietary pattern and training status can all affect appropriate nutritional planning.
The scientifically useful principle is:
Protein Alone Is Not the Same as Muscle Preservation
It is tempting to think of protein as the solution to every muscle question.
It is not.
Muscle adaptation depends on several interacting factors.
Protein intake without an appropriate mechanical stimulus is not equivalent to resistance training.
Conversely, resistance training performed during substantial energy restriction without adequate nutritional support may not provide the optimal environment for maintaining lean tissue.
This is why the emerging model is increasingly multimodal:
- Anti-obesity therapy: helps reduce excess adiposity.
- Protein adequacy: supports tissue maintenance.
- Resistance training: provides a muscle-preserving mechanical signal.
- Aerobic activity: supports cardiovascular and metabolic health.
- Body-composition monitoring: helps evaluate what is changing.
- Functional assessment: determines whether physical capacity is being preserved.
Why the Combination Looks Better Than Any Single Intervention
The 2026 meta-analysis provides an especially useful comparison.
Lifestyle intervention alone had a lean-mass proportion of approximately 26.2% of weight lost.
Incretin therapy produced proportions ranging from approximately 25% to 39% across the therapies examined.
But lifestyle intervention combined with resistance training had the most favorable pooled profile at approximately 17.5%.
This does not mean that every resistance-training program will produce exactly 17.5%.
It is a pooled estimate across heterogeneous studies.
It does suggest that resistance exercise is one of the most important modifiable components when the objective is improving the quality of weight loss.
The 2026 Evidence Also Highlights an Important Limitation
The body-composition literature is not perfectly standardized.
Studies use different technologies and definitions.
Some use DXA.
Others use MRI, CT or bioelectrical impedance.
Some measure lean mass.
Others measure fat-free mass or muscle-related indices.
Therefore, comparing percentages across studies requires caution.
A 2026 systematic review in Annals of Internal Medicine specifically highlighted the concern about changes in fat-free mass and skeletal muscle during incretin-based weight loss and emphasized the need to interpret body-composition outcomes carefully.
Why “25% Lean Mass” Should Not Become a Marketing Statistic
The number is scientifically useful.
It can also be badly misused.
It should not become:
“Tirzepatide causes 25% muscle loss.”
That statement is not supported by the evidence.
The actual evidence says that in a pooled 2026 analysis, approximately 25.4% of total weight lost with tirzepatide was categorized as lean mass.
That is a completely different statement.
Good peptide education requires preserving this distinction.
What Does the Body-Composition Goal Actually Look Like?
| Less Useful Goal | More Useful Goal |
|---|---|
| Lose as many kilograms as possible | Reduce excess adiposity while preserving lean tissue |
| Make the scale fall rapidly | Improve body composition sustainably |
| Track body weight only | Track weight, body composition and function |
| Avoid exercise because weight loss is the priority | Use resistance training as part of the weight-loss strategy |
| Eat as little as possible | Maintain adequate nutrition while reducing excess energy intake |
| Optimize scale weight | Optimize long-term health and physical capacity |
Resistance Training Is Particularly Relevant After Midlife
The muscle question becomes increasingly important with age.
Age-related changes in muscle quantity and function can reduce physical reserve.
When weight loss is added to this process, preserving functional lean tissue becomes more important.
This is why the healthy-aging perspective is different from a purely aesthetic approach.
A 65-year-old who loses excess adiposity while preserving strength may gain meaningful functional benefits even if the scale does not reach the lowest possible number.
For a long-term resident of Da Lat, that can translate into something practical:
- walking the city’s hills more comfortably;
- cycling with greater physical reserve;
- maintaining independence;
- preserving the ability to travel;
- and remaining active later in life.
The Da Lat Healthy-Aging Lens
Da Lat offers an unusual setting for thinking about weight loss.
The city is associated with cooler temperatures, walking, cycling, hiking and a slower long-stay lifestyle.
For an international resident who plans to remain in Vietnam for years rather than weeks, healthy aging can become a more relevant goal than rapid aesthetic transformation.
That changes the question from:
“How much weight can I lose?”
to:
“How can I become metabolically healthier without sacrificing the physical capacity I want to keep for the next decade?”
This is where lean-mass preservation becomes more than a technical DXA measurement.
What Should Be Monitored Beyond the Scale?
A more complete body-composition strategy can include several categories of information.
| Domain | Examples | Why It Matters |
|---|---|---|
| Body weight | Trend over time | Overall response |
| Waist circumference | Central adiposity | Relevant metabolic marker |
| Fat mass | DXA or other validated method | Shows adiposity reduction |
| Lean mass | DXA, BIA or other method | Tracks non-fat tissue changes |
| Strength | Grip, chair-rise or resistance exercise performance | Functional muscle outcome |
| Physical function | Walking, stairs, mobility | Healthy-aging relevance |
| Nutrition | Protein and micronutrient adequacy | Supports tissue maintenance |
Why Body Composition Alone Is Still Not Enough
Suppose two people both lose 20 kg.
One loses mostly fat while maintaining strength.
The other loses a similar amount of fat but experiences a meaningful decline in strength and physical function.
The scale would tell a similar story.
The biological story would be different.
This is why emerging obesity guidance increasingly emphasizes the concept of quality of weight loss.
Quality includes body composition, but also muscle function, nutritional adequacy, bone health and long-term physical capacity.
Aerobic Exercise Still Matters
Focusing on muscle preservation should not turn into an argument against cardiovascular exercise.
Aerobic activity contributes to:
- cardiorespiratory fitness;
- metabolic health;
- exercise capacity;
- blood-pressure regulation;
- and overall physical activity.
The distinction is that aerobic exercise and resistance training have different primary adaptations.
For the specific question of preserving lean tissue during weight loss, resistance training has a particularly favorable evidence base.
For healthy aging, a combination of resistance, aerobic and mobility-oriented activity may therefore be more appropriate than choosing only one exercise category.
The “Muscle-Preserving” Strategy Is Multimodal
1. Reduce Excess Adiposity
The primary therapeutic objective of obesity treatment remains clinically meaningful reduction of excess adiposity and related health risk.
2. Preserve Lean Tissue
Body-composition monitoring can help determine whether weight reduction is disproportionately affecting lean tissue.
3. Train the Muscle
Resistance exercise provides a mechanical stimulus associated with preservation of fat-free mass and improved strength during weight loss.
4. Support Nutrition
Adequate protein and overall nutritional quality become particularly important when appetite and energy intake decline.
5. Monitor Function
Strength and functional performance help translate body-composition changes into outcomes that matter for daily life and healthy aging.
Expert Insight #1: The Goal Is Not Zero Lean-Mass Change
Expert Insight: During substantial weight loss, some reduction in lean mass can occur even when treatment is highly effective. The more useful scientific objective is not to demand an unrealistic “zero lean-mass change,” but to maximize fat loss while minimizing unnecessary loss of lean tissue and preserving strength and function.
Expert Insight #2: Muscle Is a Functional Organ, Not Just a DXA Number
Expert Insight: A body-composition scan can tell you that a lean compartment changed. It cannot by itself tell you whether someone has become physically weaker or less capable. For healthy aging, lean mass should therefore be interpreted alongside resistance-training performance, strength, mobility and daily function.
Statistics & Evidence Snapshot
| Finding | Result | Interpretation |
|---|---|---|
| 2026 incretin meta-analysis | 20 RCTs; 15,782 participants | Large evidence synthesis |
| Tirzepatide | 25.4% of weight loss classified as lean mass | Lean mass is part of total weight reduction |
| Incretin therapies overall | Approximately 25%–39% | Variation exists across agents and studies |
| Lifestyle intervention | 26.2% | Comparable pooled proportion to some incretin therapies |
| Lifestyle + resistance training | 17.5% | Most favorable profile in the 2026 analysis |
| SURMOUNT-1 DXA substudy | −21.3% body weight; −33.9% fat mass; −10.9% lean mass | Fat mass reduction predominated |
| Resistance exercise meta-analysis | SMD 0.40 for fat-free-mass preservation | Moderate-certainty evidence for protection against FFM loss |
Frequently Asked Questions
Tirzepatide-associated weight loss includes reductions in lean mass as well as fat mass. However, lean mass is not equivalent to skeletal muscle, so it is inaccurate to describe the entire lean-mass reduction as muscle loss.
A 2026 meta-analysis estimated that approximately 25.4% of total weight lost with tirzepatide was lean mass. The SURMOUNT-1 DXA substudy similarly found approximately 25% of weight reduction classified as lean mass.
No. Lean-mass measurements contain more than skeletal muscle. The measurement method and body-composition definition must be considered before interpreting the result.
Current evidence supports resistance exercise as a useful strategy for attenuating fat-free-mass loss and improving strength during weight loss. A 2025 meta-analysis found moderate-certainty evidence for fat-free-mass preservation.
Tirzepatide can substantially reduce appetite and body weight. Resistance training adds a mechanical stimulus that supports preservation of lean tissue and strength during the weight-loss process.
Adequate protein is an important component of lean-mass preservation. Current obesity-treatment guidance emphasizes optimizing protein intake alongside resistance training, although appropriate intake varies between individuals.
No. Protein provides amino acids, but muscle adaptation also depends on mechanical loading, energy availability, recovery and other factors. Protein and resistance training are complementary.
Yes, the issue can become more important with aging because maintaining strength and physical function contributes to independence and resilience. Healthy aging therefore requires attention to both adiposity and functional lean tissue.
For the specific goal of preserving fat-free mass during weight loss, resistance training has a particularly favorable evidence profile. Aerobic exercise remains important for cardiovascular and metabolic health, so the two modalities serve complementary purposes.
At Week 72, pooled tirzepatide treatment was associated with approximately 21.3% body-weight reduction, 33.9% fat-mass reduction and 10.9% lean-mass reduction in the DXA substudy.
Lifestyle intervention combined with resistance training had the most favorable lean-mass proportion in the analysis, with approximately 17.5% of total weight loss classified as lean mass.
Body-composition monitoring can provide useful information, particularly when preserving lean tissue is a priority. However, results should be interpreted alongside strength, physical function and the limitations of the measurement method.
For long-term residents interested in healthy aging, preserving strength and physical capacity can be more meaningful than achieving the lowest possible body weight. Muscle function supports mobility, independence and resilience.
The injection pen is a delivery format. It does not independently determine body composition. Lean-mass outcomes depend on the underlying therapy, nutrition, physical activity, resistance training and individual biology.
Not necessarily. Some lean-mass reduction can occur during substantial weight loss. The more realistic objective is to maximize clinically beneficial fat loss while minimizing unnecessary lean-tissue loss and preserving strength and function.
Weight loss should increasingly be evaluated by its quality, not only its magnitude. Reducing excess adiposity while preserving lean tissue, strength, nutrition and physical function is a more complete definition of successful long-term weight management.
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Scientific References
- Eisa N, Barood O. Lean Mass Changes With Incretin Therapy Versus Lifestyle Intervention: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Diabetes Obes Metab. 2026;28(6):4818-4827. PMID: 41877354. DOI: 10.1111/dom.70666.
- Look M, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes Obes Metab. 2025. PMID: 39996356. DOI: 10.1111/dom.16275.
- Binmahfoz A, Dighriri A, Gray C, et al. Effect of resistance exercise on body composition, muscle strength and cardiometabolic health during dietary weight loss in people living with overweight or obesity: a systematic review and meta-analysis. BMJ Open Sport Exerc Med. 2025;11(3):e002363. PMID: 40909191. DOI: 10.1136/bmjsem-2024-002363.
- Deller M, Weiershaus J, Held S, et al. Effects of Calorie Restriction With and Without Strength, Endurance or Mixed Training on Fat-Free and Skeletal Muscle Mass in Overweight or Obese Individuals: A Systematic Review With Pairwise Meta-Analysis and Network Meta-Analysis of Randomized Controlled Studies. Diabetes Obes Metab. 2026;28(8):6810-6823. PMID: 42144246. DOI: 10.1111/dom.70873.
- Busk-Cirera L, Carlsen IØ, et al. Effects of Incretin-Based Therapies, Diet and Exercise Interventions, and Bariatric Surgery on Fat-Free Mass in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis. Diabetes Obes Metab. 2026;28(9):7737-7751. PMID: 42324178. DOI: 10.1111/dom.71006.
- Batsis JA, Gavras A, Gross DC, et al. Effect of Incretin-Based and Nonpharmacologic Weight Loss on Body Composition: A Systematic Review. Ann Intern Med. 2026;179(7):996-1013. PMID: 42258831. DOI: 10.7326/ANNALS-25-00478.
- American Diabetes Association Professional Practice Committee. Pharmacologic Treatment of Obesity in Adults: Standards of Care in Overweight and Obesity. Diabetes Care. 2026. DOI: 10.2337/doci25-0008.
- Lean Mass and Musculoskeletal Preservation in GLP-1-Based Obesity Treatment: Nutrition, Exercise, Supplementation, and Monitoring Strategies. 2026. PMID: 42346344.
- Medical Nutrition in the GLP-1 Era: Protein Strategies, Micronutrient Monitoring, and Lean Mass Preservation. Clinical Nutrition ESPEN. 2026;73:103305. DOI: 10.1016/j.clnesp.2026.103305.
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387:205-216. PMID: 35658024. DOI: 10.1056/NEJMoa2206038.
Conclusion
The next generation of weight-loss research is asking a more sophisticated question.
Not simply:
“How much weight can tirzepatide help someone lose?”
But:
“What is the quality of that weight loss?”
The answer is increasingly clear.
Tirzepatide-associated weight reduction is predominantly fat loss, but lean mass also decreases.
The SURMOUNT-1 DXA substudy found approximately 75% fat mass and 25% lean mass in the weight reduction observed with tirzepatide.
The newer 2026 meta-analysis estimated approximately 25.4% of tirzepatide-associated weight loss as lean mass, while showing a more favorable pooled profile when lifestyle intervention was combined with resistance training.
These findings do not make tirzepatide a “muscle-loss drug.”
They reveal something more important:
For healthy aging, this distinction becomes especially important.
A lighter body is not automatically a healthier body if physical capacity is simultaneously declining.
The more complete target is to reduce excess adiposity while protecting strength, lean tissue, nutrition and function.
That requires a multimodal strategy in which anti-obesity pharmacotherapy, adequate nutrition, resistance training, aerobic activity and appropriate monitoring work together.
For long-term residents in Da Lat, the healthiest endpoint may therefore not be the lowest number on the scale.
It may be the ability to remain leaner, stronger, mobile and independent for many years.
The goal is to lose excess fat while preserving the physical capacity needed for healthy aging.
Quick Answer
Core Question: Does tirzepatide cause muscle loss, how much of tirzepatide weight loss is lean mass, and how can lean mass be preserved?
Key Statistic: A 2026 meta-analysis estimated that 25.4% of tirzepatide-associated weight loss was lean mass; incretin therapies overall ranged approximately 25%–39%.
Resistance Training Finding: Lifestyle intervention plus resistance training had the most favorable pooled lean-mass proportion at approximately 17.5% of total weight loss in the 2026 meta-analysis.
SURMOUNT-1 Body Composition: Tirzepatide was associated with approximately −21.3% body weight, −33.9% fat mass and −10.9% lean mass at Week 72 in the DXA substudy.
Important Qualification: Lean mass is not synonymous with skeletal muscle. DXA, MRI, CT and BIA measure different body-composition compartments.
Muscle Preservation Framework: Resistance training + adequate protein + body-composition monitoring + functional assessment + comprehensive physical activity.
Healthy Aging Lens: For older and long-term residents in Da Lat, preserving strength, mobility and independence may be more meaningful than maximizing scale-weight reduction.
Evidence Hierarchy: Randomized clinical trials → body-composition substudies → systematic reviews/meta-analyses → mechanistic interpretation.