MetaVia's DA-1726 posts -9.1% Phase 1 weight loss and FibroScan signals at EASL Congress 2026

On May 27 at the EASL Congress 2026 in Amsterdam, a small Cambridge biotech told the room that its experimental once-weekly peptide had dropped average body weight by 9.1 percent in eight weeks, without a dose titration, and that the liver-fat and liver-stiffness signals were moving in the right direction at the same time. The compound is called DA-1726. The company is MetaVia. The trial was nine subjects in the 48 mg cohort, six of whom continued into an optional second four-week stretch. Three numbers anchor the result: −9.1 percent body weight at Day 54, −9.8 cm at the waist, and a 20 dB/m drop in FibroScan's liver-fat signal versus a 24 dB/m rise on placebo. The mechanism that produced those numbers is not the GLP-1-only story that Wegovy taught the world. It is the older, less-studied dual-receptor story that runs through retatrutide: GLP-1 plus glucagon.

The Numbers, In Order

The 48 mg cohort enrolled nine subjects, randomized 2-to-1 to DA-1726 or placebo, dosed once weekly subcutaneously for four weeks with no titration. Six of the nine continued into an optional four-week extension at the same dose. The primary endpoint was safety. The signals that brought the abstract to a late-breaking session were secondary.

Mean body weight fell 6.1 percent by Day 26 (p < 0.05 vs placebo), and 9.1 percent by Day 54. The curve had not flattened by Week 8. Waist circumference moved on a similar trajectory: −5.8 cm at Day 26, −9.8 cm at Day 54 (p < 0.05 vs placebo at Day 26). For a four-week dosing window with one optional extension, those are larger numbers than the field has produced before from an oxyntomodulin-class peptide at this stage.

On the liver side, the exploratory FibroScan findings were what brought hepatologists into the room. Controlled attenuation parameter — CAP, which estimates hepatic steatosis — fell 20.0 dB/m in the DA-1726 group and rose 24.0 dB/m on placebo. Liver stiffness on VCTE dropped 10.3 percent from baseline on drug, against a 13.8 percent rise on placebo. The composite FibroScan-AST (FAST) score, which combines stiffness with serum AST and CAP to estimate MASH activity, moved directionally in DA-1726's favor. These are surrogate measures, not biopsy. They are also the measures most MASH programs are now using to triage which assets advance.

The safety picture was uneventful for an incretin-class compound dosed at 48 mg without titration. No serious adverse events. No treatment-related discontinuations. Gastrointestinal AEs were primarily mild-to-moderate and transient. Despite glucagon receptor agonism — the historical worry being heart rate or QTcF prolongation — no clinically meaningful changes in either parameter were seen.

What the Mechanism Actually Does

The reason a dual GLP-1/glucagon agonist is interesting in 2026, when semaglutide and tirzepatide have already redrawn the obesity market, comes down to where each receptor does its work.

The GLP-1 receptor is on pancreatic beta cells, on neurons in the hypothalamus and brainstem, and on the gut. Activate it and you get more insulin in response to glucose, slower gastric emptying, and a centrally mediated drop in appetite. That is the Wegovy/Ozempic story. It does not, on its own, do much to liver fat beyond what weight loss alone delivers.

The glucagon receptor is mostly hepatic. Activate it and the liver burns more fat. It also raises basal energy expenditure — calories out — in a way GLP-1 alone does not. The historical reason no one wanted a glucagon-only drug is that the glucagon receptor also drives hepatic glucose production, which is exactly the wrong direction for a diabetes drug. The peptide design problem for the last fifteen years has been figuring out the right balance between GLP-1's appetite-and-glucose effects and glucagon's energy-and-liver effects, so that the diabetes downside is suppressed by the GLP-1 side while the weight and liver upside is amplified by the glucagon side.

Oxyntomodulin, the endogenous 37-amino-acid gut peptide that activates both receptors at once, is the natural starting point for that design exercise. DA-1726 is an engineered oxyntomodulin analogue with extended half-life sufficient for once-weekly dosing. The Phase 1 readout is the first sustained-dose look at whether the balance MetaVia chose actually produces the dual-mechanism effect on the human body. The body-weight curve — driven mostly by the GLP-1 component plus some thermogenesis — and the liver curve — driven mostly by the glucagon component plus weight loss — moving together is what a balanced dual agonist is supposed to look like.

Where This Sits Against The Competition

The comparator everyone in the room was running in their head was retatrutide, Eli Lilly's triple GLP-1/GIP/glucagon agonist. Retatrutide's TRIUMPH-4 Phase 3 trial reported a 28.7 percent body weight reduction at 68 weeks — the highest figure produced by any pharmaceutical agent to date. Retatrutide has three receptor levers; DA-1726 has two. The trial durations are not comparable; 8 weeks of Phase 1 cannot be projected to 68-week Phase 3 outcomes. But the Day 54 trajectory of −9.1 percent without a plateau, in a study with no dose titration, is in the range where a longer trial extrapolates to something that competes credibly on weight loss while potentially differentiating on liver biomarkers.

EB618, an oral oxyntomodulin-class GLP-1/glucagon dual agonist, sits in the same mechanistic family and is pursuing the opposite route-of-administration strategy — a once-daily oral tablet. The trade is convenience versus exposure. A weekly injection produces steadier plasma levels; a daily oral tablet substitutes patient preference for pharmacokinetic smoothness. DA-1726's data, if confirmed in larger studies, will sharpen the comparison between these two delivery models within the same mechanism.

The newest entrant is Kailera and Hengrui's KAI-4729, a triple GLP-1/GIP/glucagon agonist with Phase 1 data also presented in May 2026, showing up to 16 percent weight loss at 12 weeks at the top dose in a Chinese trial. The triple-G arms race has, in other words, started crowding. DA-1726's pitch in that field is not "highest weight loss" — that title belongs to retatrutide. It is "weight loss plus MASH biomarker improvement in a single agent." Whether that pitch holds depends on what FibroScan and FAST signals look like in a longer, larger study.

MetaVia, listed on Nasdaq as MTVA, is a small-cap clinical-stage biotech in Cambridge, Massachusetts. CEO Hyung Heon Kim and CMO Chris Fang presented the data. Companies of MetaVia's size in this space usually pursue partnership rather than a solo Phase 3, particularly given how capital-intensive obesity Phase 3 programs have become. The EASL readout is the kind of data the market reads as a partnership-positioning event.

What the Trial Does Not Yet Show

Nine subjects in the active arm, six in the extension. Phase 1. No biopsy. No A1c readout reported in the press summary. No body composition imaging that separates fat-mass loss from lean-mass loss — the latter being the longstanding concern with high-dose multi-receptor agonists, since a portion of the weight loss in retatrutide trials was lean tissue. No data on muscle preservation. No dose comparison; only 48 mg.

The FibroScan findings are exploratory and surrogate. A 20 dB/m drop in CAP corresponds, very roughly, to one stage of hepatic steatosis improvement on imaging. That is suggestive but not adjudicated. Real MASH trials require biopsy endpoints — at minimum, resolution of steatohepatitis without worsening of fibrosis at a defined timepoint. None of that is in the EASL data.

The Phase 1 Part 3 titration studies — designed to evaluate longer-term dosing strategies and optimize tolerability at higher exposures — are the next-step readout the company has flagged. MetaVia has not publicly committed to a Phase 2 design or to a Phase 2 start date. Capital and partnership decisions hang on the Part 3 data and on how the broader incretin field absorbs the result.

The MASH Question Behind All of This

Metabolic dysfunction-associated steatohepatitis, formerly NASH, is an inflammatory liver disease that progresses from steatosis (fat) to steatohepatitis (fat plus inflammation) to fibrosis to cirrhosis. It affects roughly five percent of the global adult population, and the only fully FDA-approved MASH drug to date is resmetirofin (Madrigal's thyroid hormone receptor-β agonist Rezdiffra), approved in 2024 for non-cirrhotic MASH with moderate-to-advanced fibrosis. GLP-1 receptor agonists have shown MASH benefit indirectly — via the substantial weight loss they cause — and Novo Nordisk's ESSENCE trial of semaglutide met both MASH endpoints in 2024.

The question DA-1726 implicitly poses is whether a dual GLP-1/glucagon agonist can do better than GLP-1 alone on the liver, because the glucagon component is acting directly on hepatocyte lipid metabolism rather than only via the systemic weight-loss effect. The EASL data does not answer that question. It is suggestive in the right direction. A controlled head-to-head against semaglutide at matched weight-loss endpoints, with biopsy-confirmed MASH outcomes, is what would actually answer it. No such trial is currently announced.

The Investor and Prescriber Read

For investors, the read is binary along two axes. First, does the weight-loss curve scale? If a 4-to-8 week 9.1 percent figure scales linearly toward Phase 3-relevant timepoints, DA-1726 enters retatrutide-comparison territory; if the curve plateaus aggressively in the Part 3 titration study, the molecule becomes a niche MASH play rather than an obesity-and-MASH play. Second, does a major buyer surface? Mid-cap obesity assets at this stage typically resolve via license deal, partnership, or acquisition. The audience for that resolution is the small set of large pharmas without a triple-G or oxyntomodulin candidate already in-house.

For prescribers, the read is "watch, do not act." DA-1726 is investigational. There is no compounding pathway, no off-label option, and no clinical context in which it is appropriate to source or prescribe outside an enrolled trial. The mechanism is interesting, the data is suggestive, and the time horizon to FDA review — assuming Phase 2 starts in late 2026 or 2027 — is at least three years from now in the most optimistic scenario.

Frequently Asked Questions

What is oxyntomodulin, and why is it the basis for DA-1726?

Oxyntomodulin is a 37-amino-acid peptide hormone released by intestinal L-cells after meals. It is one of several post-translational products of the preproglucagon precursor, alongside GLP-1 and glucagon itself. Oxyntomodulin happens to activate both the GLP-1 receptor and the glucagon receptor with a balance that, in human physiology studies dating back to the early 2000s, reduces food intake and raises resting energy expenditure simultaneously. The native peptide is broken down within minutes by dipeptidyl peptidase-4, the same enzyme that degrades GLP-1. Peptide engineering — protease-resistant residue substitutions, lipid acylation for albumin binding — produces analogues with half-lives long enough to dose once weekly. DA-1726 is one such engineered analogue.

How does a glucagon-receptor agonist not raise blood sugar?

It does, in isolation. But the GLP-1 receptor agonism on the same molecule drives glucose-dependent insulin secretion and slows gastric emptying, both of which counteract the glucagon-driven hepatic glucose output. The net effect, in balanced dual agonists, is glucose-neutral or glucose-lowering — depending on the exact receptor selectivity ratio. Phase 1 trials of DA-1726 have not reported a glucose-worsening signal at the doses tested. Longer studies will look more carefully at A1c.

How does DA-1726 differ from retatrutide?

Retatrutide is a triple agonist — GLP-1, GIP, and glucagon. DA-1726 is a dual agonist — GLP-1 and glucagon only. The GIP component in retatrutide is believed to contribute additional appetite suppression and to modulate adipose tissue insulin sensitivity. Removing GIP simplifies the receptor balance and may affect lean-mass preservation, an open question in this drug class. The clinical consequence — whether DA-1726's two-receptor design produces meaningfully different efficacy or safety than retatrutide's three-receptor design — will be answered, if at all, by longer trials.

Will compounding pharmacies be able to make DA-1726?

Almost certainly not, even if it is eventually approved. The 503A compounding pathway requires that the active pharmaceutical ingredient either be on the FDA's bulks list or be derived from an FDA-approved product. A novel patented peptide owned by MetaVia (or a future licensee) would not be eligible for compounding. The "research-grade" peptide market does occasionally produce knockoffs of investigational compounds — see the Alabama Board of Medical Examiners' May 26, 2026 notice — but these carry the same verification problems as all unapproved peptides. Patients should not seek out compounded or research-grade versions of DA-1726.

When could DA-1726 actually reach patients?

The earliest realistic FDA approval timeline, assuming a successful Phase 2 in 2027 and a Phase 3 in 2028–2029, is approximately 2030 or later. Most Phase 1 oncology and obesity assets do not reach approval at all. Even within the obesity class, where the regulatory pathway is well-trodden, attrition between Phase 1 and Phase 3 remains substantial.

What should I watch for next?

The Phase 1 Part 3 titration data, expected later in 2026 per MetaVia's investor communications, is the next milestone. It will address dose-response, tolerability at higher exposures, and the durability of the weight-loss and liver-biomarker effects beyond eight weeks. A partnership announcement, if one comes, is the second event to watch.

Sources

• MetaVia Inc. "MetaVia Presents Higher-Dose Phase 1 Results for DA-1726 at EASL Congress 2026, Supporting Potential in Obesity and MASH." PR Newswire, May 27, 2026.
• MetaVia Inc. "MetaVia to Present DA-1726 Late-Breaking Poster at EASL Congress 2026." PR Newswire, May 11, 2026.
• BioPharma Dive. "Kailera's three-pronged obesity shot shows promise in early trial." May 27, 2026.
• European Association for the Study of the Liver. "EASL Congress 2026." Amsterdam, May 27–31, 2026.
• Madrigal Pharmaceuticals. "FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease (Rezdiffra/resmetirom)." March 14, 2024.
• Newsome PN et al. "Semaglutide in Adults with Steatohepatitis (ESSENCE trial)." New England Journal of Medicine, 2024.