Monday's data sharpened the oral GLP-1 competitive map. Lilly's Foundayo (orforglipron) leads with a Phase 3 head-to-head win over oral semaglutide and a Q2 FDA filing pending. Structure's aleniglipron sits closest, with 16.3% Phase 2b weight loss and Nature Medicine publication on Friday. AstraZeneca's elecoglipron just cleared Phase 2b. Chinese entrants Hengrui-Kailera (ribupatide, HRS-7535) added Phase 2 and 3 readouts. Novo's Wegovy pill remains the only currently-approved oral, but the next-wave field is now broad and head-to-head data are arriving fast.
A Medscape ADA wrap on June 8 framed the post-GLP-1 era taking shape across the meeting: amylin analogs (petrelintide, cagrilintide, eloralintide) targeting GI-intolerance, triagonists (retatrutide), antibody-peptide conjugates (Amgen's maridebart cafraglutide/MariTide), and preclinical acceleration through AI peptide-design platforms. Each angle aims at the population gap that current GLP-1 monotherapy leaves: the patients who quit for tolerability, the ones who plateau, and the ones who need additional metabolic effects beyond appetite.
EASL 2026's first two days clarified the MASH-therapeutics competitive map across five mechanism classes. GLP-1/glucagon dual peptides: Altimmune pemvidutide (48-week IMPACT data, Best of EASL), Boehringer survodutide (NEJM 47-62% MASH improvement, LIVERAGE Phase 3), MetaVia DA-1726 (48 mg Phase 1). THR-β agonists: Madrigal Rezdiffra (only FDA-approved MASH therapy, eight EASL posters), Aligos ALG-055009 (46.2% liver-fat reduction Phase 2a). RNAi: Arrowhead ARO-INHBE (Activin E/ALK7, 44% liver fat, tirzepatide combination). FASN inhibition: Sagimet denifanstat + Rezdiffra combination. FGF21 analogs: the Akero efruxifermin (Novo $5.2B acquisition) and 89bio pegozafermin (Roche $3.5B acquisition) programs anchoring the most-acquired MASH mechanism. Plus galectin-3 inhibition (Galectin belapectin NAVIGATE) and pan-PPAR agonism (Inventiva lanifibranor NATiV3 Phase 3). The GLP-1/glucagon peptide class leads on combined weight-loss-plus-liver effect; the FGF21 and THR-β classes lead on pure antifibrotic mechanism. Combination therapy across mechanism classes is the emerging 2026 thesis.