GLP-1/glucagon dual receptor agonists pair the appetite-suppression and metabolic effects of GLP-1 with the direct hepatic effects of glucagon-receptor activation — reduced liver fat, inflammation, and fibrosis, plus increased resting energy expenditure. The combination neutralizes glucagon's standalone glucose-raising risk while amplifying fat-burning. The class has emerged as the leading peptide mechanism for MASH (metabolic dysfunction-associated steatohepatitis) where the liver-directed glucagon arm matters most.
The 2026 competitive cohort: Boehringer Ingelheim's survodutide (BI 456906, partnered with Zealand Pharma) posted full 48-week Phase 2 MASH data in NEJM at EASL 2026 — MASH improvement without fibrosis worsening in 47-62% of patients versus 14% placebo, with Phase 3 LIVERAGE and LIVERAGE-Cirrhosis enrolling. Altimmune's pemvidutide (balanced 1:1 GLP-1/glucagon) earned 'Best of EASL 2026' for its IMPACT Phase 2b data, with the 48-week oral presentation showing triglyceride, cholesterol, weight, and waist reductions. MetaVia's DA-1726 (3:1 ratio oxyntomodulin analog) presented Phase 1 higher-dose data at EASL. Eli Lilly's retatrutide adds GIP to the GLP-1/glucagon backbone as a triple agonist.
Stories here cover the dual-agonist trial readouts, the MASH and obesity competitive landscape, and the broader incretin-mechanism field. See #survodutide, #pemvidutide, and #mash for adjacent threads.
At ADA 2026 on Sunday June 7, Innovent presented the Phase 3 GLORY-2 trial of mazdutide 9 mg in Chinese adults with obesity, presented by Leili Gao of Peking University People's Hospital. The dual GLP-1/glucagon agonist drove up to 20.1% mean weight loss and met its primary endpoint and all key secondary endpoints. The result extends China's homegrown obesity-peptide leadership, with mazdutide already approved by China's NMPA in 2025.
Boehringer Ingelheim and Zealand Pharma presented the full Phase 3 SYNCHRONIZE-1 readout for survodutide, the glucagon/GLP-1 dual agonist, at ADA 2026. In adults with obesity or overweight without type 2 diabetes, survodutide produced up to 16.6% mean weight loss at 76 weeks versus 3.2% placebo (p<0.0001), with up to 85.1% achieving at least 5% loss. Analyst attention now turns to body composition and liver-fat substudies, with reductions driven largely by fat-tissue loss rather than lean mass.
Full Phase 3 SYNCHRONIZE-1 results for the glucagon/GLP-1 dual agonist survodutide are set for ADA 2026, detailing the obesity readout first toplined in April. In adults with obesity or overweight without type 2 diabetes, survodutide produced up to 16.6% mean weight loss at 76 weeks versus 3.2% on placebo, with up to 85.1% of treated patients losing at least 5% of body weight. The full dataset puts survodutide's glucagon component, which adds energy expenditure and liver-fat effects, in front of the field that gathers in New Orleans.
MetaVia's higher-dose Phase 1 readout for DA-1726 at EASL 2026 produced specific efficacy numbers: the 48 mg cohort in obese but otherwise healthy adults achieved 9.1% mean body-weight reduction and a 9.8 cm waist-circumference reduction at Day 54, with exploratory FibroScan liver improvements and no serious adverse events. DA-1726 is a once-weekly subcutaneous oxyntomodulin analog acting as a 3:1 ratio GLP-1/glucagon dual receptor agonist for obesity and MASH. The 9.1% weight loss in roughly eight weeks is a fast trajectory for an early-phase obesity peptide and supports MetaVia's case heading into the 16-week Phase 1 Part 3 titration study reading out Q4 2026. The waist reduction (a glucagon-receptor-driven visceral-fat signal) and the FibroScan liver improvements position DA-1726 in the dual obesity-and-MASH lane alongside survodutide and pemvidutide. MetaVia's three ADA 2026 late-breaking abstracts (June 7 New Orleans) extend the DA-1726 and vanoglipel data sets.
Altimmune presented the full Week 48 top-line IMPACT Phase 2b oral data for pemvidutide in MASH today at EASL 2026 Barcelona (Dr. Mazen Noureddin, Houston Methodist Hospital, 17:00 CEST). The 1.8 mg dose reduced triglycerides 23.7%, total cholesterol 15.4%, body weight 7.5%, BMI 3.0 kg/m², and waist circumference 5.3 cm, alongside blood pressure reduction. Safety held at 48 weeks with roughly 1% discontinuation due to adverse events and mostly mild-to-moderate gastrointestinal events. Previously reported: 27.8% (1.2 mg) and 32.4% (1.8 mg) of patients achieved combined ELF and LSM improvements versus 3.2% on placebo. The 48-week analysis carries the 'Best of EASL 2026' designation. Pemvidutide is a balanced 1:1 GLP-1/glucagon dual receptor agonist peptide with FDA Fast Track + Breakthrough Therapy Designations for MASH. The cardiometabolic-risk-factor profile positions pemvidutide as differentiated on the lipid and cardiovascular axis versus pure GLP-1 agonists.
Boehringer Ingelheim's survodutide full 48-week Phase 2 MASH dataset published in the New England Journal of Medicine alongside the EASL 2026 presentation. MASH improvement without worsening of fibrosis occurred in 47% of the 2.4 mg group, 62% of the 4.8 mg group, and 43% of the 6.0 mg group, versus 14% on placebo. Up to 52% of survodutide-treated adults achieved significant improvement across fibrosis stages F1, F2, and F3 versus around 26% on placebo. Survodutide is an investigational long-acting glucagon/GLP-1 receptor dual agonist (BI 456906, partnered with Zealand Pharma) for once-weekly subcutaneous administration. The Phase 3 program is advancing through LIVERAGE (~1,800 adults with MASH F2-F3) and LIVERAGE-Cirrhosis (~1,590 adults with compensated MASH cirrhosis F4). Survodutide also posted 16.6% weight loss in the SYNCHRONIZE-1 obesity Phase 3 (April 2026). The NEJM publication is the strongest peer-reviewed validation of the GLP-1/glucagon dual mechanism in MASH to date.
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.
MetaVia presented late-breaking Phase 1 data on DA-1726 at the EASL Congress 2026 today in Barcelona. The poster titled 'Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DA-1726, an Oxyntomodulin Analogue, in a Higher-Dose Phase 1 Cohort with Exploratory Noninvasive Liver Assessment' covers the 48 mg dose level. DA-1726 is a once-weekly subcutaneous oxyntomodulin analog functioning as a GLP-1 receptor (GLP1R) and glucagon receptor (GCGR) dual agonist for obesity and MASH. The 4-week Phase 1 MAD trial earlier in 2026 documented compelling weight loss with best-in-class potential glucose control (GLP-1R arm), waist reduction (GCGR arm), and tolerability profile. The current 16-week Phase 1 Part 3 titration study is designed to optimize higher-dose levels and tolerability with full data expected Q4 2026. The EASL poster extends the early-phase MASH biomarker package and supports the planned Phase 2 advancement.
Altimmune presents IMPACT Phase 2b clinical trial data on pemvidutide in metabolic dysfunction-associated steatohepatitis (MASH) at the European Association for the Study of the Liver Congress 2026 (May 27-30 Barcelona). The randomized, placebo-controlled, double-blind Phase 2b trial enrolled 212 biopsy-confirmed MASH patients with fibrosis stages F2 or F3 (with and without diabetes), randomized 1:2:2 to weekly subcutaneous pemvidutide 1.2 mg, 1.8 mg, or placebo for 48 weeks. The late-breaking poster Wednesday May 27 at 08:30 CEST reports the AI-based Liver Explore quantitative digital pathology analysis showing significant reductions in proportionate areas of early, advanced, and total liver fibrosis at 24 weeks. The non-invasive PRO-C3:CTX-III ratio reduced consistent with fibrosis regression. Pemvidutide is a GLP-1/glucagon dual-action peptide with FDA Fast Track designation for MASH plus Breakthrough Therapy Designation. The approach competes directly with Boehringer Ingelheim's survodutide and Eli Lilly's retatrutide on the GLP-1/glucagon arm for MASH.
Following the April 28 SYNCHRONIZE-1 obesity topline (16.6% weight loss at 76 weeks), Boehringer Ingelheim and Zealand Pharma confirmed that survodutide — their dual GLP-1/glucagon agonist — has two global Phase 3 MASH trials underway: LIVERAGE in adults with MASH and fibrosis stages F2 or F3, and LIVERAGE-Cirrhosis in compensated MASH cirrhosis. The Phase 3 program follows Phase 2 data showing 83% of MASH patients achieved histological improvement at 48 weeks. The MASH track positions survodutide alongside tirzepatide's SYNERGY-NASH and broader Lilly Phase 3 activity in the metabolic-liver-disease space, with full SYNCHRONIZE-1 data slated for ADA 2026 in June.