MetaVia Inc. has announced promising Phase 1 results for DA-1726, a novel dual oxyntomodulin analog agonist targeting obesity treatment, showing clinically meaningful weight loss without requiring dose titration. The data, presented at ObesityWeek 2025, demonstrated that participants receiving the highest tested dose of 32 mg achieved body weight reductions of up to 6.3% from baseline, with an average reduction of 4.3% at Day 26.
Clinical Trial Results Show Strong Efficacy Signal
The Phase 1 randomized, double-blind, placebo-controlled study evaluated DA-1726 in obese but otherwise healthy adults with a body mass index of 30-45 kg/m². Each of the four cohorts included nine participants randomized 6:3 to receive four once-weekly subcutaneous doses of DA-1726 or placebo.
Beyond weight loss, participants experienced substantial waist circumference reductions, with decreases of as much as 3.9 inches. These effects were sustained for two weeks after dosing ended, suggesting durable metabolic benefits.
"These Phase 1 results continue to reinforce DA-1726's potential as a differentiated dual agonist for the treatment of obesity," said Hyung Heon Kim, Chief Executive Officer of MetaVia. "The favorable safety profile observed, even without titration, together with potentially best-in-class early weight loss, waist circumference reduction and clean cardiovascular findings, is highly encouraging."
Pharmacokinetic Profile Supports Once-Weekly Dosing
The newly reported pharmacokinetic data revealed linear, dose-proportional exposure and a mean half-life of approximately 80 hours, confirming the feasibility of once-weekly dosing. This extended half-life supports patient convenience and treatment adherence compared to more frequent dosing regimens.
DA-1726 was well tolerated across all dose levels, with no serious adverse events or treatment discontinuations reported. Gastrointestinal events were mild and transient, and no clinically meaningful changes were observed in cardiovascular parameters, including heart rate or QTcF interval.
Preclinical Data Demonstrates Superior Lipid Benefits
Comparative preclinical studies in diet-induced obesity mouse models showed DA-1726's differentiated metabolic profile compared to other dual agonists. When compared to tirzepatide, DA-1726 produced greater weight loss despite similar food intake, accompanied by enhanced energy expenditure not attributable to increased locomotor activity.
"DA-1726 demonstrated comparable weight-loss efficacy to pemvidutide while delivering superior lipid-lowering effects, including greater reductions in total cholesterol and LDL-C," Kim noted. The drug also led to greater reductions in total cholesterol and LDL-C, demonstrating a distinct glucagon-mediated metabolic mechanism.
When compared with pemvidutide, DA-1726 achieved similar body-weight reductions and improvements in body composition, including decreased fat mass and relatively preserved lean mass. Notably, DA-1726 delivered superior lipid-lowering benefits, showing greater reductions in total cholesterol, LDL-C, and triglycerides across treatment groups.
Mechanism of Action and Development Strategy
DA-1726 functions as a dual agonist of GLP-1 receptors (GLP1R) and glucagon receptors (GCGR), leading to weight loss through reduced appetite and increased energy expenditure. As an oxyntomodulin analog, it mimics a naturally-occurring gut hormone that activates both receptor types, potentially resulting in superior body weight loss compared to selective GLP1R agonists.
Based on the encouraging Phase 1 results, MetaVia has extended the study to evaluate a 48 mg dose for a total of 8 weeks to assess longer-term early efficacy and patient exposure while exploring the non-titrated maximum tolerated dose. Results from the 48 mg cohort are expected later this year.
The company is developing DA-1726 for both obesity and Metabolic Dysfunction-Associated Steatohepatitis (MASH), positioning it as a potential treatment for multiple cardiometabolic conditions. The drug is administered once weekly subcutaneously, offering a convenient dosing schedule for patients.
