Myostatin Drugs Advance With GLP-1 Combos
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- Myostatin-blocking drugs are being tested in humans after early failures, with newer approaches targeting both myostatin and activin A to boost muscle mass more effectively than blocking myostatin alone.
- Regeneron tested a triple therapy of semaglutide, trevogrumab, and garetosmab in obese monkeys, resulting in lean mass gain and greater fat loss, but a third of participants in the human phase II trial stopped due to severe side effects.
- Trevogrumab, a myostatin precursor-targeting antibody, halved lean mass loss when combined with semaglutide in humans, showing promise despite safety concerns from off-target effects.
- Apitegromab, another myostatin precursor blocker, reduced lean mass loss in phase II trials and improved motor function in children with spinal muscular atrophy in a phase III trial, with potential FDA approval for this use by September.
- David Glass at Regeneron notes that while muscle gains in humans are capped at around 10%—far below animal results—the real goal is maintaining mobility and strength in older adults, not bodybuilding.
- Brendan Gabriel at the University of Aberdeen emphasizes that muscle plays a key role in metabolic health by storing blood sugar and could help treat obesity and diabetes if boosted safely.
Why it matters: Older adults and people on GLP-1 drugs stand to benefit from preserved muscle mass and metabolic function if myostatin blockers like apitegromab prove safe, but severe side effects in trials so far limit near-term use. The 10% muscle increase ceiling and trial dropouts signal a high bar for widespread adoption.
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