Effect of GLP-1 receptor agonists at doses for obesity management on muscle health: systematic review and meta-analysis of randomized controlled trials (RCTs).

Laverde LP, Muñoz-Velandia OM, Alfonso D, Gómez Medina AM

International journal of obesity (2005)19 Jun 2026

PMID42321502PMCIDPMC13461373DOI10.1038/s41366-026-02118-yPepBankPUB-42321502

Summary

IntroductionThe impact of GLP-1 receptor agonists (GLP1-RA) treatment on lean mass and body composition in patients with obesity is not fully understood.MethodologySystematic review and meta-analysis of RCTs including patients with obesity treated with GLP1-RA at obesity doses, compared with placebo. Search was conducted in PubMed, Embase, and LILACS in March 2025. A meta-analysis was performed using a random-effects model to evaluate the change in lean mass as a proportion of total weight, the absolute and relative changes in lean mass, and adverse effects.ResultsSeven studies (821 patients) were included in the analysis. GLP1-RA significantly improved lean mass as a proportion of total weight, with an observed increase of 1.81% (95% CI: 1.1- 2.52; p < 0.00001; I² = 7%). However, a significant decrease was observed in the absolute change in lean mass (-1.74 kg; 95% CI: -3.04 to -0.45; p < 0.00001; I² = 98%) and in the percentage of lean mass (-3.06%; 95% CI: -5.10 to -1.02; p < 0.00001; I² = 98%). Semaglutide demonstrated the most significant reduction in absolute lean mass, with a loss of -5.44 kg (95% CI: -7.07 to -3.81; p < 0.00001).ConclusionsThere is an improvement in body composition due to an increase in lean mass as a proportion of total weight, an effect that could be amplified with the use of semaglutide. Our results suggest that lean mass loss should not be considered a limitation for the use of these drugs in patients with obesity. However, it is essential to accompany drug treatment with nutritional and physical exercise interventions to preserve or improve muscle mass and optimize clinical outcomes.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

1 result from studies that gave the peptide. 1 result from people.

01HumanSystematic reviewEfficacy outcome
In adults with obesity, semaglutide had the largest reduction in absolute lean mass among the drugs, -5.44 kg versus placebo.
In plain wordsIn adults with obesity, people on semaglutide lost more lean mass (in kilograms) than people on placebo, and the most among the GLP-1 drugs studied.
Peptide
Semaglutide
Outcome
DecreaseAbsolute lean mass change with semaglutide
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body composition · Metabolic and weight
Studied dose
Dose not stated
Measurements
Absolute lean mass change
−5.44 kg
semaglutide
Source sentences
Summary
Semaglutide demonstrated the most significant reduction in absolute lean mass, with a loss of -5.44 kg (95% CI: -7.07 to -3.81; p < 0.00001).
2 context sentences(design, population, supporting numbers)
Summary · context
Systematic review and meta-analysis of RCTs including patients with obesity treated with GLP1-RA at obesity doses, compared with placebo.
Summary · context
Seven studies (821 patients) were included in the analysis.
Show in the study text Report a problemFND-4232150204

Studies that did not test the peptide alone3

In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Semaglutide.

02HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with obesity, pooled GLP-1 receptor agonists at obesity doses (including semaglutide) increased lean mass as a proportion of total weight by 1.81% versus placebo.
In plain wordsIn adults with obesity, GLP-1 drugs as a group raised the share of body weight that is lean mass, compared with placebo.
Peptide
Semaglutide
Outcome
IncreaseLean mass as a proportion of total weight
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body composition · Metabolic and weight
Measurements
Change in lean mass proportion
1.81%
pooled GLP-1 RA
Source sentences
Summary
GLP1-RA significantly improved lean mass as a proportion of total weight, with an observed increase of 1.81% (95% CI: 1.1- 2.52; p < 0.00001; I² = 7%).
2 context sentences(design, population, supporting numbers)
Summary · context
Systematic review and meta-analysis of RCTs including patients with obesity treated with GLP1-RA at obesity doses, compared with placebo.
Summary · context
Seven studies (821 patients) were included in the analysis.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4232150201
03HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with obesity, pooled GLP-1 receptor agonists at obesity doses (including semaglutide) reduced absolute lean mass by 1.74 kg versus placebo.
In plain wordsIn adults with obesity, GLP-1 drugs as a group lowered the total amount of lean mass compared with placebo.
Peptide
Semaglutide
Outcome
DecreaseAbsolute change in lean mass
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body composition · Metabolic and weight
Measurements
Absolute lean mass change
−1.74 kg
pooled GLP-1 RA
Source sentences
Summary
a significant decrease was observed in the absolute change in lean mass (-1.74 kg; 95% CI: -3.04 to -0.45; p < 0.00001; I² = 98%)
2 context sentences(design, population, supporting numbers)
Summary · context
Systematic review and meta-analysis of RCTs including patients with obesity treated with GLP1-RA at obesity doses, compared with placebo.
Summary · context
Seven studies (821 patients) were included in the analysis.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4232150202
04HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with obesity, pooled GLP-1 receptor agonists at obesity doses (including semaglutide) reduced the percentage of lean mass by 3.06% versus placebo.
In plain wordsIn adults with obesity, GLP-1 drugs as a group lowered the percentage change in lean mass compared with placebo.
Peptide
Semaglutide
Outcome
DecreasePercentage change in lean mass
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body composition · Metabolic and weight
Measurements
Percentage lean mass change
−3.06%
pooled GLP-1 RA
Source sentences
Summary
in the percentage of lean mass (-3.06%; 95% CI: -5.10 to -1.02; p < 0.00001; I² = 98%).
2 context sentences(design, population, supporting numbers)
Summary · context
Systematic review and meta-analysis of RCTs including patients with obesity treated with GLP1-RA at obesity doses, compared with placebo.
Summary · context
Seven studies (821 patients) were included in the analysis.
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4232150203

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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