An agent session, step by step
Question: Do GLP-1 receptor agonists cause loss of lean muscle mass, and how large is it relative to weight lost?
An unedited production session against https://mcp.machinelibrary.ai/, abbreviated for reading: snippets are cut to 260 characters, fetched text to 600, the passage to 500, and the sources to the first 12 of 27. The answer is complete.
Recorded · session JSON
1. Search the library
machinelibrary_search_documents6.0 s
The agent searches documents for the topic and asks for five results.
Arguments
{
"query": "GLP-1 receptor agonists lean muscle mass loss semaglutide tirzepatide",
"limit": 5
}Result
- 1.
Greater lean-body-mass decline with tirzepatide than semaglutide in routine care, revealed by body-composition digital phenotyping
https://doi.org/10.64898/2026.04.11.26350687GLP-1 receptor agonists induce substantial weight loss, but the extent to which lean tissue and physical function are preserved in routine care remains poorly understood. Using an EHR-linked body-composition digital phenotyping pipeline with LLM-based extracti…
- 2.
Greater lean-body-mass decline with tirzepatide than semaglutide in routine care, revealed by body-composition digital phenotyping
https://doi.org/10.21203/rs.3.rs-9407186/v1GLP-1 receptor agonists induce substantial weight loss, but the extent to which lean tissue and physical function are preserved in routine care remains poorly understood. Using an EHR-linked body-composition digital phenotyping pipeline with LLM-based extracti…
- 3.
A Narrative Review on GLP-1 Receptor Agonists for Obesity in Older Women: Maximizing Weight Loss While Preserving Lean Mass
https://doi.org/10.3390/nu18040632Clinical trials have demonstrated that approximately 25–40% of the total weight loss observed with GLP-1 receptor agonists (GLP-1 RAs) is attributable to the loss of lean mass, including muscle. This proportion of lean mass loss is of particular clinical conce…
- 4.
EFFECTS OF SEMAGLUTIDE AND TIRZEPATIDE ON SKELETAL MUSCLE MASS AND SARCOPENIA RISK IN ADULTS WITH OBESITY OR OVERWEIGHT: A NARRATIVE REVIEW
https://doi.org/10.31435/ijitss.3%2851%29.2026.6230Background: GLP-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP agonists are highly effective therapies for obesity management. However, associated reductions in lean body mass have raised concerns regarding sarcopenia risk. This review evaluated whether th…
- 5.
GLP-1 agonists and exercise: the future of lifestyle prioritization
https://doi.org/10.3389/fcdhc.2025.1720794Clinical studies using DEXA show that GLP-1–based weight loss is accompanied by some loss of lean mass, but fat loss predominates. In STEP-1 (semaglutide), lean mass decreased by ~9.7% while fat mass fell by ~19.3%, with the proportion of lean mass increasing …
Hits 1 and 2 are the same study: its medRxiv preprint and its Research Square preprint. They have different DOIs and are returned as separate records.
2. Fetch one document
machinelibrary_fetch_document0.2 s
The agent opens the narrative review from hit 4 by its URI and caps the text at 4,000 characters.
Arguments
{
"uri": "https://doi.org/10.31435/ijitss.3(51).2026.6230",
"max_chars": 4000
}Result
EFFECTS OF SEMAGLUTIDE AND TIRZEPATIDE ON SKELETAL MUSCLE MASS AND SARCOPENIA RISK IN ADULTS WITH OBESITY OR OVERWEIGHT: A NARRATIVE REVIEW
https://doi.org/10.31435/ijitss.3%2851%29.2026.6230Background: GLP-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP agonists are highly effective therapies for obesity management. However, associated reductions in lean body mass have raised concerns regarding sarcopenia risk. This review evaluated whether these changes translate into clinically relevant sarcopenia or sarcopenic obesity. Methods: A narrative review of the PubMed, Cochrane Library and Google Scholar databases was conducted up to May 2026, to evaluate GLP-1 receptor agonist effects on muscle mass, body composition, and sarcopenia-related outcomes. Results: GLP-1 RAs produced su…
max_chars bounds how much text comes back, and billing counts only the returned text, so it also bounds the cost of the call. The URI was sent with plain parentheses; the response gives the canonical source_uri to cite.
Fields in the response:
abstractabstract_truncatedauthorscomment_countcommentscontentcontent_truncateddocument_typefull_content_lengthfull_reference_countidissued_atissued_at_datetimelanguagesnext_stepnotepublisherreferenced_byreferencesreferences_truncated
3. Search inside the document
machinelibrary_search_in_document0.8 s
The agent asks the same document for the passage on lean mass as a share of weight lost.
Arguments
{
"uri": "https://doi.org/10.31435/ijitss.3(51).2026.6230",
"query": "lean mass loss as a proportion of total weight lost"
}Result
Background: GLP-1 receptor agonists (GLP-1 RAs) and dual GLP-1/GIP agonists are highly effective therapies for obesity management. However, associated reductions in lean body mass have raised concerns regarding sarcopenia risk. This review evaluated whether these changes translate into clinically relevant sarcopenia or sarcopenic obesity. Methods: A narrative review of the PubMed, Cochrane Library and Google Scholar databases was conducted up to May 2026, to evaluate GLP-1 receptor agonist effec…
This record's text is its abstract only, so the best passage is the abstract itself.
4. Get a cited answer
machinelibrary_research12.7 s
The agent asks the research tool, which answers from retrieved sources and numbers its citations.
Arguments
{
"query": "Do GLP-1 receptor agonists such as semaglutide and tirzepatide cause loss of lean muscle mass, and how large is it relative to total weight lost?"
}Result
Short answer
Yes. GLP-1 receptor agonists (GLP-1RAs) such as semaglutide and dual agonists such as tirzepatide reduce lean mass along with fat mass. In the main trials, lean mass loss accounts for roughly 25% to 45% of total weight lost, depending on the drug, the study, and the measurement method. In absolute terms, the loss is larger with greater total weight loss, and the proportion is not uniformly higher than with diet or surgery.
Size of lean loss relative to weight lost
Semaglutide (STEP 1): In the DXA substudy, lean mass fell by 6.92 kg (−13.2%) out of 15.3 kg total weight loss, or 45.2% of weight lost [1][2]. Other sources give about 39–40% [3][4][5]. Lean mass fell while fat mass fell more, and the lean-to-body-mass ratio rose [6][7].
Tirzepatide (SURMOUNT-1): Lean mass fell by 5.67 kg (−10.9%) out of 22.1 kg total weight loss, or 25.7% [1][2]. Other reports give about 25% [6][8][9].
Other agents and settings: A SUSTAIN-8 substudy in type 2 diabetes found lean loss of 43.4% of weight lost, while lean mass as a share of body mass increased slightly [1][10]. Liraglutide has been reported at up to 60% in one overview [11], though this is described as a possible outlier [12].
Pooled estimates: A network meta-analysis of 22 RCTs (2258 participants) found lean mass loss of about 25% of total weight lost, while relative lean mass (percentage of body weight) was unchanged [13][14]. Tirzepatide 15 mg and semaglutide 2.4 mg were among the least effective at preserving lean mass [13][15].
Why the figures vary
- Measurement: DXA measures lean mass, which includes organs, water, and bone, not only skeletal muscle [16][17]. About 73% of lean mass is water, so DXA-recorded losses overstate true muscle protein loss [18].
- Trial conditions: Trials included lifestyle counselling, which may have reduced muscle loss [19][7].
- Population: Losses appear larger in non-diabetic patients [20].
- Comparators: The proportion is comparable to that from dietary restriction (about 25%) and bariatric surgery [4][21].
Clinical interpretation
Some authors argue that the loss is partly adaptive, since MRI studies show reduced muscle fat infiltration and stable or improved muscle quality [3][22]. Others note that absolute losses exceed normal age-related decline, which is roughly 0.4–0.5% per year [1]. Functional data are limited. Most trials report preserved or improved self-reported function, and objective strength data are sparse [19][23]. Older adults and people with sarcopenia or low muscle reserve are the most concerning groups [24][25].
Mitigation
Resistance training and adequate protein intake are the main recommended strategies, though randomized data specific to GLP-1RAs are lacking [26][27]. Investigational agents such as bimagrumab, which increased lean mass by 3.6% and reduced fat mass by 20.5% in one cited study, are under study [24][9].
First 12 of 27 sources
Citations [13] to [27] in the answer refer to sources not listed here.
- [1]
Emerging Frontiers in GLP-1 Therapeutics: A Comprehensive Evidence Base (2025)
https://doi.org/10.3390/pharmaceutics17081036 - [2]
New drugs for the treatment of obesity: do we need approaches to preserve muscle mass?
https://doi.org/10.1007/s11154-025-09967-4 - [3]
Obesity medications and precision nutrition: synergistic interventions and integrated approach in obesity management
https://doi.org/10.1007/s13679-026-00695-7 - [4]
Beyond Weight Loss: Optimizing GLP-1 Receptor Agonist Use in Children
https://doi.org/10.3390/children12111427 - [5]
Glucagon-like peptide-1 receptor agonists and aesthetic surgery: perioperative safety, timing, durability and body composition
https://doi.org/10.3389/fendo.2026.1969433 - [6]
GLP-1 agonists and exercise: the future of lifestyle prioritization
https://doi.org/10.3389/fcdhc.2025.1720794 - [7]
Unintended Consequences of Obesity Pharmacotherapy: A Nutritional Approach to Ensuring Better Patient Outcomes
https://doi.org/10.3390/nu17111934 - [8]
Preservation of lean soft tissue during weight loss induced by GLP-1 and GLP-1/GIP receptor agonists: A case series
https://doi.org/10.1177/2050313x251388724 - [9]
Saving muscle while losing weight: A vital strategy for sustainable results while on glucagon-like peptide-1 related drugs
https://doi.org/10.4239/wjd.v16.i9.109123 - [10]
Greater lean-body-mass decline with tirzepatide than semaglutide in routine care, revealed by body-composition digital phenotyping
https://doi.org/10.64898/2026.04.11.26350687 - [11]
Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies
https://doi.org/10.1111/dom.15728 - [12]
Effects of Blood-Glucose Lowering Therapies on Body Composition and Muscle Outcomes in Type 2 Diabetes: A Narrative Review
https://doi.org/10.3390/medicina61081399
Why it matters for agents
Every result carries a canonical source_uri, so the agent cites the record it read instead of reconstructing a reference. Full text is bounded by max_chars, so a fetch fits a known token budget. Passages can be located inside one document without fetching all of it.
Connect your agent
Server URL: https://mcp.machinelibrary.ai
Claude Code
claude mcp add --transport http --scope user machinelibrary https://mcp.machinelibrary.aiCursor and Windsurf
{
"mcpServers": {
"machinelibrary": {
"type": "http",
"url": "https://mcp.machinelibrary.ai"
}
}
}