What Does the Research Say About Lean Mass Preservation?
A research-supply overview of experimental strategies for lean mass preservation, including multi-receptor agonists and antibody-based approaches, with evidence from animal and clinical studies.
Lean mass preservation refers to the maintenance of skeletal muscle and other non-fat tissues during periods of weight reduction. In the research literature, this concept is often studied in the context of obesity pharmacotherapy, where interventions that promote fat loss may also affect lean mass. The formal term 'lean mass preservation' is used interchangeably with 'muscle mass preservation' or 'fat-free mass preservation' in study protocols. Identifiers such as sequence, formula, or molecular weight are not provided in the evidence block for this topic.
The work centres on the glucagon-like peptide-1 receptor (GLP-1R) pathway and emerging multi-receptor agonists, as well as antibody-based inhibition of signalling pathways that regulate muscle growth.
Research Studies
Multi-receptor agonists and lean mass preservation in obesity models
Obesity affects over 2 billion adults globally, with projections indicating that nearly two-thirds of adults will be affected by 2050. GLP-1 receptor agonists (GLP-1RAs) have transformed obesity treatment, achieving weight loss previously considered attainable only with bariatric surgery. However, GLP-1-based therapies have revealed important limitations, including weight loss plateaus, substantial inter-individual variability, and weight regain upon discontinuation, underscoring the need for next-generation approaches. Existing reviews have focused predominantly on approved GLP-1RAs, with limited synthesis of emerging multi-receptor agonists, oral formulations, and body composition outcomes [1].
Trevogrumab and garetosmab with semaglutide in adults with obesity
A clinical study is testing trevogrumab or trevogrumab with garetosmab when taken with semaglutide in adult patients with obesity for weight loss, fat loss, and lean mass preservation. The study is researching experimental drugs called trevogrumab and garetosmab (called 'study drugs') in combination with another drug, semaglutide (Wegovy®). This study will be done in 3 parts, Part A, Part B, and Part C where different study drugs will be tested. Part A of the study is focused on healthy participants. Part B and C of the study are focused on participants with obesity. The aim of Part A of the study is to see how safe and tolerable the study drug is in healthy participants. The aim of Part B and Part C of the study is to see how safe and effective the study drug is when combined with Wegovy. Parts A, B, and C of the study are looking at several other research questions [2].
Comparison of study parts in NCT06299098
| Study Part | Population | Primary Aim |
|---|---|---|
| Part A | Healthy participants | Safety and tolerability of study drug |
| Part B | Participants with obesity | Safety and efficacy of study drug with Wegovy |
| Part C | Participants with obesity | Safety and efficacy of study drug with Wegovy |
Limitations of GLP-1-based therapies for lean mass preservation
GLP-1-based therapies have revealed important limitations, including weight loss plateaus, substantial inter-individual variability, and weight regain upon discontinuation, underscoring the need for next-generation approaches. Existing reviews have focused predominantly on approved GLP-1RAs, with limited synthesis of emerging multi-receptor agonists, oral formulations, and body composition outcomes [1].
Emerging multi-receptor agonists and body composition outcomes
Existing reviews have focused predominantly on approved GLP-1RAs, with limited synthesis of emerging multi-receptor agonists, oral formulations, and body composition outcomes [1].
Antibody-based approaches for lean mass preservation in obesity
A clinical study is testing trevogrumab or trevogrumab with garetosmab when taken with semaglutide in adult patients with obesity for weight loss, fat loss, and lean mass preservation [2].
Safety and tolerability of trevogrumab in healthy participants
The aim of Part A of the study is to see how safe and tolerable the study drug is in healthy participants [2].
Efficacy of trevogrumab with semaglutide in participants with obesity
The aim of Part B and Part C of the study is to see how safe and effective the study drug is when combined with Wegovy [2].
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Sources
- [1] Obesity pharmacotherapy reimagined: The era of multi-receptor agonists and next-generation metabolic modulators, perspectives and controversies.
- [2] A Study to Test if Trevogrumab or Trevogrumab With Garetosmab When Taken With Semaglutide is Safe and How Well They Work in Adult Patients With Obesity for Weight Loss, Fat Loss, and Lean Mass Preservation