Eugene Lucas, MD
Semaglutide and tirzepatide have dramatically altered obesity treatment. Significant weight loss is now more achievable than ever before, and additional weight loss medications of similar or greater potency will probably become available in the coming years.
Greater amounts of weight loss are not without potential for downsides, however, namely the potential for the loss of lean body mass (LBM), which can compromise strength and function. As loss of LBM and strength are associated with both reduced quality of life and increased mortality risk, clinician-supported weight loss plans should include a focus on each to provide a comprehensive approach toward optimizing overall health.
Why Is Lean Body Mass Important?
Muscle mass, often clinically quantified as LBM or fat-free mass (FFM), plays a crucial role in metabolic health, physical functioning, and quality of life (Wolfe R; Srikanthan P, Karlamangla A; Srikanthan P, Karlamangla A; Tagliaferri C, et al).
Some key definitions:
FFM refers to the summed mass of water, protein, glycogen, minerals, and bone.
LBM is typically defined as FFM minus bone weight.
Sarcopenia is a clinical syndrome in which adverse changes to muscle, usually as an effect of the aging process, result in decreases in strength and physical function.
Peak LBM occurs around 40 years and declines at 4.7% per decade in men and 3.7% in women. LBM significantly decreases with weight loss, accounting for around 22% of total weight lost after bariatric surgery (Carrasco F, et al; Martínez MC, et al) and 34.8% with semaglutide use.
Low LBM has been associated with increased risk for all-cause mortality (Li R, et al; Abramowitz MK, et al) and reduced length of life (Srikantha P, Karlamangla A). When LBM is assessed together with strength, strength has been shown to have a greater impact on all-cause mortality (Newman AB, et al); in fact, low muscle strength confers an increased risk for all-cause mortality even in the presence of adequate LBM (Li R, et al).
How to Assess Lean Body Mass
The 2016 Comprehensive Clinical Practice Guidelines for the Medical Care of Patients With Obesity mention that a body composition assessment (BCA) can be considered to provide more accurate measurements of adiposity, but not for LBM. Instead, the authors recommend hand grip strength assessments on the basis that they are “cheaper and as clinically relevant as measuring muscle mass.”
Given the decreased costs and increased accessibility of BCAs, along with the clinical insights gained from assessing LBM, the use of BCAs in clinician-supported weight loss plans appears both reasonable and warranted. The Table provides a comparison of the various body composition assessments.
Table. Comparison of Various Body Composition Methodologies
Methodology Pros Cons
MRI Highest accuracy for BCA High cost
CT Highest accuracy for BCA High cost
High radiation exposure
DEXA Approximates accuracy of MRI/CT
Relatively low cost (~$200)
Low radiation exposure (1/100th of upper limit of annual exposure) Modest radiation exposure
Modest out-of-pocket cost if not covered by insurance
BIA Reasonably accurate
Variable cost
Allows frequent tracking at home
No radiation exposure More convenient than DEXA
Overestimates LBM and underestimates fat mass
BCA = body composition assessment; BIA = bioelectrical impedance analysis; CT = computed tomography; DEXA = (dual-energy x-ray absorptiometry); MRI = magnetic resonance imaging
Given that low muscle strength confers an increased risk for all-cause mortality, even in individuals with normal LBM, clinician-supported weight loss plans should include strength assessments.
Despite evidence that hand grip strength may not correlate with overall strength (Tieland M, et al), and conflicting evidence as to whether it can be improved through strength training (Labott BK, et al; Carneiro MA, et al), hand grip strength has been shown to correlate with all-cause mortality, disease-specific mortality, and quality of life (Bohannon RW, et al).
Measuring hand grip strength is quick and safe and can be performed using a compact dynamometer (about $300 for a clinical validated device).
Assessment of hand grip strength is generally more important in older adults, but clinicians should consider it in younger individuals as well to establish a baseline for future comparisons.
Because hand grip strength doesn’t provide information on lower extremity strength, clinicians should consider performing a sitting-rising test or a chair stand test, which both have a statistically significant relationship with all-cause mortality and can be used to identify individuals with low muscle strength (Brito LB, et al; Cesari M, et al).
Regular strength training helps increase LBM. Repeat BCA can determine the impact of strength training on LBM development and maintenance.
How to Preserve Lean Body Mass
Given the risks to LBM resulting from weight loss, patients should receive guidance on strategies to preserve both LBM and strength. Consuming adequate amounts of protein daily and regular strength training are both of paramount importance.
While the minimum amount of protein and strength training required to preserve lean mass for individuals is unclear, current evidence suggests that a clinician-supported weight loss plan aimed at providing the greatest health benefit would prioritize a high-protein diet (> 1.5 grams of protein per kilogram of body weight per day [g/kg/d] or about two times the recommended dietary allowance) and at least twice-weekly strength training.
General Guidelines and Supporting Evidence
More protein, regardless of type, generally provides greater benefit, with peak benefit occurring at a consumption of about 1.5 g/kg/d.
The recommended dietary allowance for protein, defined as 0.8 g/kg/d, impairs muscle protein synthesis and results in LBM loss, even in young, healthy individuals.
In protein type comparisons (eg, whey vs soy, whey vs pea, and whey vs casein), no statistically significant benefit for LBM was found.
In older adults and frail individuals who were not in a caloric deficit, performing strength training twice per week in combination with consuming 1.3 g/kg/d of protein resulted in LBM increases relative to those of participants who consumed 1.0 g/kg/d of protein. Separately, without an assessment for strength training, older men who consumed 1.6/g/kg/d of protein increased LBM and showed improvement on various strength/functional assessments relative to those who consumed 0.8 g/kg/d.
A systematic review and meta-analysis demonstrated that, in the absence of a caloric deficit, individuals who took part in strength training experienced a peak strength benefit at a protein intake of 1.5 g/kg/d.
The amount of protein consumed at mealtime affects benefit and is enhanced by strength training.
Muscle protein synthesis is stimulated in relation to the amount of protein consumed and temporal proximity of muscle contraction activity, with some evidence suggesting a greater mealtime protein requirement for older adults.
In healthy men and women (mean age, 37 years) consuming equal amounts of total daily protein expressed as g/kg/d, consumption of around 30 g of protein three times per day resulted in 25% greater muscle protein synthesis relative to those who consumed more than half of their total daily protein at dinnertime.
With a combination of regular strength training and adequate protein intake, it may be possible to prevent loss of LBM while losing weight.
A 4-week study consisting of a 40% daily caloric deficit and a robust exercise regimen was performed to assess the impact of two amounts of daily protein consumption:
Exercise regimen: 2 days of full body resistance training plus 4 days of mixed aerobic and resistance training per week
Group A consumed 1.2 g/kg/d of protein and lost weight while preventing decreases in LBM.
Group B consumed 2.4 g/kg/d of protein and lost more weight than Group A while generating increases in LBM.
Frequency and duration of strength training affects benefit; individuals should aim for at least two strength training sessions per week with a goal of 60 minutes of total strength training time per week.
In older adults who were not in a caloric deficit, two sessions of strength training per week led to a fourfold increase in LBM relative to the group that participated in one session per week.
Peak all-cause mortality risk reduction occurs at 60 minutes of total strength training time per week.
In the absence of strength training, high protein consumption (1.7 g/kg/d) did not prevent decreases in LBM and strength among older individuals adhering to a 25% daily caloric deficit.
Strength training routine recommendations should follow evidence-based guidelines.
According to the American College of Sports Medicine and the American Heart Association, strength training sessions should be targeted to all major muscle groups, consist of 8-12 repetitions for each exercise, and be performed at least twice per week on nonconsecutive days.
Protein supplementation has been shown to increase levels of satiety-promoting hormones such as glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK), which can assist with reductions in caloric intake.
Given that the goal for daily protein consumption may be difficult for individuals to achieve on a regular basis through food sources alone, and because low-cost, high-protein, low-calorie protein supplements are readily available, these appear worthy of incorporating into clinician-supported weight loss plans.
For individuals with a history of chronic kidney or liver disease, daily protein consumption at amounts greater than the recommended dietary allowance can worsen these conditions; thus, the goal protein recommendations above would not be appropriate for these populations.
In Summary
Patients should be informed of the risks of LBM and strength decreases as a result of both increased age and weight loss, with greater emphasis on the risks to muscle mass for patients achieving significant medication-associated weight loss.
Patients should receive education on strategies to preserve and/or increase both LBM and strength as part of clinician-supported weight loss plans, including recommendations on adequate protein consumption and regular strength training.
Body composition and strength assessments should be performed at the onset of clinician-supported weight loss plans. These assessments generally should be repeated annually to track body composition and strength changes as a result of weight loss and age. In certain scenarios — including but not limited to those below — it would be reasonable to consider repeating a BCA at 6 months:
Total body weight loss of 15% or greater during a 6-month timeframe
Low appendicular lean mass index (ALMI) found on initial BCA. A reasonable definition for low ALMI is ≤ 40th percentile according to population-level data for the patient’s demographics.
BCA results should be reviewed by the treating clinicians, and the implications should be incorporated into individualized weight loss plans, with greater emphasis on protein intake and strength training provided to patients with inadequate LBM.
Obesity treatment plans using semaglutide and tirzepatide provide patients with an opportunity to improve their health by reducing excess weight, but these medications also carry a risk for accelerated muscle mass reduction and diminished strength, which would adversely affect overall health. Clinicians who prescribe these medications have a responsibility to their patients to inform them of these risks, offer risk assessment, and provide guidance on strategies to offset these risks.
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