MetaVia Expands GLP-1 Glucagon Receptor Agonist Obesity Trial Amid Signs of Superior Tolerability

MetaVia announced that it has extended the 48 mg multiple ascending dose (MAD) cohort of its Phase I trial (NCT06252220) for DA-1726—a dual GLP-1 and glucagon receptor agonist for obesity—from four weeks to eight weeks. According to the company, the extension includes administration of a fifth weekly dose to the first patient and is designed to explore the non-titrated maximum tolerated dose, as well as longer-term safety, tolerability, and early efficacy outcomes.¹

Why Is MetaVia Doubling the Dosing Period for DA-1726?

"Extending DA-1726 administration by an additional four weeks—for a total of eight weeks—in the 48 mg cohort represents a meaningful step forward as we seek to evaluate longer-term early efficacy and patient exposure to DA-1726, while also exploring the non-titrated maximum tolerated dose," stated Hyung Heon Kim, President, CEO, MetaVia, in a press release. "After reviewing the original trial design and previous results, we feel confident that the four-week extension can potentially provide more robust data, which we believe may position DA-1726 more strongly against current treatments and those in late-stage clinical trials.”

Trial Overview and Patient Profile

The randomized, double-blind, placebo-controlled trial is currently evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of single and multiple ascending doses of DA-1726 in obese but otherwise healthy adults. Enrolled patients have a body weight between approximately 190 lbs and 285 lbs. Participants in each cohort were randomly assigned in a 6:3 ratio to receive either four weekly administrations of DA-1726 or placebo.

Trial Extension and Study Endpoints

The extended cohort will receive once-weekly doses of either DA-1726 or placebo for a total of eight weeks. The trial’s primary objective is to assess the safety and tolerability of DA-1726 by tracking adverse events (AEs), including serious and treatment-emergent AEs, as well as any that lead to discontinuation. Secondary endpoints include PK, measured by serum drug concentrations over time and metabolite profiling at higher doses.¹

Early Results Show Promise

“By extending exposure to the drug, we aim to more fully evaluate DA-1726's therapeutic profile across primary, secondary and exploratory endpoints—including safety, tolerability, body weight, waist circumference, and body mass index (BMI), among others—and to further unlock its full therapeutic potential,” continued Kim, in the press release. “Previously reported data from the 32 mg dose demonstrated strong weight loss effects (mean: 4.3%, max: 6.3% by Day 26), early satiety in 83% of patients, and waist reductions of up to 3.9 inches by Day 33. These findings, along with favorable glycemic and cardiovascular safety and a mild, transient GI profile, suggest that DA-1726-may offer a superior tolerability profile compared to existing GLP-1 therapies."

Strategic Partnership Supports Pipeline Expansion

The trial extension follows MetaVia’s recent partnership announcement with Syntekabio. This week, the company disclosed a research collaboration with the AI-driven drug discovery firm to identify additional indications for DA-1241, its oral GPR119 agonist currently in development for cardiometabolic diseases. The collaboration includes access to Syntekabio’s DeepMatcher platform, which uses AI to predict interactions between small molecules and target proteins—an essential step in modern drug discovery.²

Looking Ahead

Topline data from the extended 48 mg cohort is now expected in the fourth quarter of 2025.¹

"We continue to believe that DA-1726's 3:1 balanced activation of GLP-1 and glucagon receptors may offer a differentiated safety profile that addresses the well-documented tolerability issues seen with current GLP-1 agonists, where discontinuation rates reach 20–30% within the first month and up to 70% within a year,” concluded Kim, in the press release. “We look forward to reporting top-line data from the extended 48 mg cohort later this year, which may further validate DA-1726's longer-term safety, early efficacy and differentiated tolerability profile compared to current GLP-1 therapies."

References

1. MetaVia Extends 48 mg MAD Portion of Its Phase 1 Clinical Trial of DA-1726 for the Treatment of Obesity to 8 Weeks and Announces Fifth Weekly Dose in First Patient. PR Newswire. August 6, 2025. Accessed August 6, 2025. https://prnmedia.prnewswire.com/news-releases/metavia-extends-48-mg-mad-portion-of-its-phase-1-clinical-trial-of-da-1726-for-the-treatment-of-obesity-to-8-weeks-and-announces-fifth-weekly-dose-in-first-patient-302522928.html
2. MetaVia, Syntekabio Partner to Expand Indications for Oral MASH Drug Using AI Drug Discovery. PharmExec. August 5, 2025. Accessed August 6, 2025. https://www.pharmexec.com/view/metavia-syntekabio-partner-expand-indications-oral-mash-drug-ai-drug-discovery