Part of the weight people lose on GLP-1 drugs is muscle and other lean tissue. In Regeneron's COURAGE trial, about a third of the weight lost on semaglutide alone over 26 weeks was lean mass, and drugmakers are now testing add-on drugs to keep it.
Regeneron's trevogrumab, an antibody that blocks the muscle-limiting protein myostatin, leads that effort. In 52-week COURAGE results reported on October 1, 2026, adding trevogrumab 25 or 75 mg to semaglutide limited lean mass loss to 5.8% and 4.2%, versus 7.3% on semaglutide alone, without adding much to weight loss. An earlier triple combination with garetosmab preserved more lean mass at 26 weeks, but 28.3% of that group stopped treatment and two participants died, deaths Regeneron did not link to the drugs. Not every program has held up: on September 28, 2026, Roche dropped its anti-myostatin antibody emugrobart for obesity after an interim look at its Phase 2 GYMINDA trial.
See #myostatin, #sarcopenia, and #glp-1-side-effects.
Researchers at the Federal University of Santa Catarina in Brazil reported in Diabetes, Obesity and Metabolism on October 19, 2026 a systematic review of 11 studies measuring muscle strength in adults on semaglutide. Pooling 10 studies with 660 participants, the average change in handgrip strength was -0.16 kgf, not statistically significant, with very large differences between studies and very low certainty of evidence. The authors said current data cannot show whether semaglutide changes muscle strength.
A retrospective study from two centers in Palermo, Italy, published online September 25, 2026 in the Journal of Diabetes and Its Complications and reported by News-Medical on October 2, followed 122 adults with overweight or obesity and no diabetes who took tirzepatide alongside a standardized low-carbohydrate diet and tailored exercise. After 24 weeks, at a mean final dose of 5.32 mg, average weight fell from 95 kg to 80 kg, fat mass fell 35.4% and fat-free mass 5.1% on bioelectrical impedance, and the authors reported that skeletal muscle was preserved. The study had no control group, used bioimpedance rather than DXA scans, and included only people who completed the 24 weeks.
Chugai announced on Monday, September 28, 2026 that Roche is discontinuing development of emugrobart (GYM329), a subcutaneous anti-latent myostatin antibody, for obesity after an interim analysis of the Phase 2 GYMINDA study concluded that the trial was unlikely to meet its pre-specified weight-loss objectives. GYMINDA tested emugrobart in combination with GLP-1/GIP receptor agonists in people with obesity or overweight; Chugai said the antibody was well tolerated, with no new safety signals. All rights return to Chugai, which is preparing to resume development in spinal muscular atrophy and considering out-licensing; Roche had already stopped emugrobart development in spinal muscular atrophy and facioscapulohumeral muscular dystrophy in March 2026.
Follow-through analyst commentary Tuesday August 25, 2026 on the Monday Roche (SIX: ROG) and Hanmi Pharm HM17321 urocortin-2 (UCN2) obesity licensing deal positioned Roche as now targeting a top-three global obesity commercial position behind Eli Lilly (Zepbound, Mounjaro, Foundayo, and upcoming retatrutide) and Novo Nordisk (Wegovy, Ozempic, Wegovy Pill, Wegovy HD, CagriSema under review). Deal recap: $190 million upfront, up to $2.3 billion in milestones, plus tiered royalties; Genentech gets global rights excluding South Korea. HM17321 mechanism: a proprietary urocortin-2 (UCN2) analog peptide that selectively activates the corticotropin-releasing factor 2 receptor (CRFR2), a mechanism distinct from the incretin pathway (GLP-1, GIP) that anchors every currently-approved obesity drug. Roche obesity portfolio positioning: HM17321 combines with Roche's existing CT-388 (a dual GIP/GLP-1 receptor agonist acquired in the December 2023 Carmot Therapeutics acquisition for $2.7 billion, currently in Phase 2 for obesity and type 2 diabetes) and the emerging Roche obesity pipeline including RG7500 orforglipron precursor and other early-stage assets. The multi-mechanism portfolio provides a differentiated commercial positioning to compete across weight-loss efficacy (Roche's incretin agonist candidates match Lilly and Novo) and muscle-preservation (HM17321's differentiated UCN2 mechanism designed for lean mass preservation). Roche's obesity ambition contrasts with prior investor skepticism about its late-cycle entry into the category; Tuesday's analyst commentary suggests the multi-mechanism strategy could position Roche credibly for 2028-2030 commercial launches assuming pipeline programs advance to registration.
Hanmi Pharm (KRX: 128940) signed Monday August 24, 2026 an exclusive licensing agreement with Genentech (a member of the Roche Group) for HM17321, a proprietary urocortin-2 (UCN2) analog peptide for obesity. Deal terms: $190 million upfront payment, up to $2.3 billion in development, regulatory, and commercial milestone payments, plus tiered royalties on sales. Territory: Genentech secures global rights excluding South Korea, where Hanmi retains the license. Mechanism: HM17321 selectively activates the corticotropin-releasing factor 2 receptor (CRFR2), a peptide-hormone receptor pathway distinct from the incretin pathway (GLP-1 receptor, GIP receptor) that anchors every currently-approved obesity drug including semaglutide, tirzepatide, orforglipron, and the broader GLP-1 receptor agonist class. Urocortin-2 is a naturally occurring 38-amino-acid peptide of the corticotropin-releasing factor family. Differentiated profile: HM17321 is positioned as a potential first-in-class treatment designed to simultaneously promote weight loss and preserve lean body mass, an important differentiator against the semaglutide-tirzepatide-retatrutide GLP-1 class where roughly 25% of the total weight lost is lean muscle mass. Development pathway: Hanmi received FDA IND clearance to initiate a Phase 1 clinical trial in November 2025. Hanmi is responsible for completing the Phase 1 clinical trial, after which Genentech will take over development starting with Phase 2 clinical trials. The deal represents one of the largest 2026 obesity licensing transactions and adds a substantially different mechanism to Roche's obesity portfolio that also includes CT-388 (dual GIP/GLP-1 agonist from the Carmot Therapeutics acquisition).
Pep2Tango Therapeutics presented preclinical data on PTT-A, a novel long-acting unimolecular peptide tetra-agonist activating the GLP-1, GIP, amylin, and calcitonin receptors simultaneously, in a Medscape 'Moving Beyond GLP-1s' feature drawing from the ADA 2026 session 'Novel Strategies for Obesity Pharmacology' (oral abstracts 85-OR and 299-OR, Diabetes journal supplement). In 21-day chronic studies in diet-induced obese rats, the higher PTT-A dose achieved 19% body weight reduction versus the vehicle, compared to 12% each for tirzepatide and cagrilintide + semaglutide (CagriSema). Body composition analysis showed fat-mass loss without lean-mass loss, distinguishing PTT-A's profile from tirzepatide's documented muscle-loss pattern. PTT-A also showed robust glucose lowering, plasma lipid improvement, insulin sensitization, and liver-fat benefits.
Hanmi Pharmaceutical presented HM500197 (LA-MSTN) at ADA 2026 (June 5-8, New Orleans) as the world's first peptide-based myostatin inhibitor, positioned as a muscle-preserving adjunct to GLP-1 weight-loss therapy. The molecule was designed on Hanmi's HARP (Hanmi AI-driven Research Platform) integrating AI and structural modeling. Hanmi paired the LA-MSTN unveiling with a second next-generation candidate, HM17321, in a broader eight-abstract slate spanning the company's obesity pipeline. The myostatin angle addresses a major shortcoming of the current GLP-1 class — 25-40% of weight loss coming from lean tissue rather than fat — which Stanford's Maharjan team flagged at ENDO 2026 with the 560-step daily activity drop and which underlies the broader bone-health and frailty concerns now being studied across the GLP-1 class.
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.