Muscle preservation has emerged as the most studied side of the GLP-1 era. Up to 40% of incretin-driven weight loss in the highest-loss patients lands on lean mass, and Nature Reviews Endocrinology has flagged sarcopenia and frailty as under-recognized GLP-1 side effects — particularly in adults over 65 and patients with pre-existing low muscle mass.
Covered here: Regeneron's REGN1033 (trevogrumab) Phase 2 COURAGE trial with semaglutide showing the myostatin antibody preserves lean mass during GLP-1-driven weight loss; Ascletis's ASC47, an adipose-targeting thyroid hormone receptor beta (THRβ) agonist that delivered up to 111.8% greater relative weight loss when combined with semaglutide in obesity participants vs semaglutide monotherapy (ECO 2026 May 14 poster session); Lilly's bimagrumab follow-on through the Versanis acquisition; and a 2026 Journal of Cachexia, Sarcopenia and Muscle scoping review documenting peptide candidates across MIF1/MIF2 myostatin inhibitors and GH-axis peptides like CJC-1295, ipamorelin, and tesamorelin.
Stories here cover the combination-with-incretin strategies, the myostatin program readouts, and the broader sarcopenia therapeutic landscape. See #myostatin, #sarcopenia, and #glp-1-side-effects.
Ascletis Pharma will present multiple poster sessions at ECO 2026 covering programs beyond the already-presented ASC30. ASC47, an adipose-targeting thyroid hormone receptor beta (THRβ) agonist designed for muscle-preserving weight loss, demonstrated up to 111.8% greater relative weight loss when combined with semaglutide vs semaglutide monotherapy in obesity participants. ASC36, a once-monthly next-generation amylin receptor agonist peptide, posted a 32-day average observed half-life — six times longer than Zealand's petrelintide. ASC35, a once-monthly next-generation GLP-1R/GIPR dual agonist peptide, showed a 14-day average observed half-life (six times longer than tirzepatide) and 71% more relative weight loss than tirzepatide in a diet-induced obesity mouse model. Session Thursday May 14, 18:00-19:15 TRT.
Scholar Rock's apitegromab — a selective pro/latent myostatin antibody approved for SMA — continues to draw obesity-pipeline attention with EMBRAZE Phase 2 data showing 54.9% relative lean mass preservation when combined with tirzepatide vs tirzepatide alone (4.2 lbs / 1.9 kg additional lean mass preserved, p=0.001). Body composition shifted from 70% fat/30% lean with tirzepatide alone to 85%/15% with the combination. SRK-439 next-gen selective myostatin inhibitor is in preclinical development with attenuation of fat-mass rebound after GLP-1 withdrawal as a key signal.
Regeneron's COURAGE Phase 2 data presented at EASD 2025 continue to drive obesity-pipeline conversations. Semaglutide alone produced 6.5% lean mass loss at 26 weeks; sema + trevogrumab 200 mg cut that to 3.3% (~half), and the triplet with garetosmab (anti-activin A) pushed to 2.0% lean mass loss with 92.6% fat-mass loss. The triplet had higher discontinuation for tolerability. Full COURAGE completion is expected late 2026, with Phase 3 initiation likely 2027.