Macro partitioning
Combining GLP-1 receptor agonists with myostatin or activin type II receptor inhibitors (e.g., bimagrumab, trevogrumab, garetosmab) preserves or increases lean mass while enhancing fat loss, addressing the risk of sarcopenia and metabolic slowdown associated with standard AOM therapy.
Current GLP-1 therapies can lead to muscle loss, which may hinder long-term weight maintenance. Emerging combination therapies that pair GLP-1 agonists with muscle-preserving antibodies (like bimagrumab or myostatin inhibitors) show promise in preclinical models for doubling fat loss while increasing lean mass. Patients should discuss these emerging options with their providers, especially if they are concerned about muscle loss.
preclinical studies in diet-induced obese mice have shown co-therapy to achieve equal body weight-lowering efficacy to semaglutide, but with significantly greater fat mass loss, lean mass preservation, and reductions in food intake... in obese male cynomolgus monkeys, semaglutide-based tri-therapy with trevogrumab... and garetosmab... doubled fat mass loss (50% vs. 25%) and increased lean mass by 11.7% relative to semaglutide treatment alone
Why this rating
Based on preclinical (mouse/monkey) studies and ongoing phase 2 trials; human data is not yet fully published.
Source
Why are we still in need for novel anti-obesity medications?
Aaron Novikoff et al. · The Lancet Regional Health - Europe · 2024
DOI 10.1016/j.lanepe.2024.101098
More from this paper
- Current GLP-1-based anti-obesity medications (AOMs) achieve profound acute body weight loss (up to 25%) but are associated with significant real-world treatment discontinuation (up to 50%) due to gastrointestinal side effects and lack of lifestyle counseling, necessitating novel formulations with improved tolerability.Good
- Weight regain after discontinuation of GLP-1-based AOMs is an inherent feature of current pharmacological strategies, but future interventions such as gene therapy (GLP-1PGTx) or gradual dose-tapering may mitigate this by sustaining hormonal signals or allowing hormonal adaptation.Moderate
Related findings · Macro partitioning
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