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June 7, 2026

3102-LB: Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DA-1726, an Oxyntomodulin Analogue: Phase 1 Higher-Dose Cohort Results

Key Points

The aim was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of DA-1726 in obese adults.
Phase 1 randomized trial with a higher-dose cohort of 48 mg.
Nine participants received either DA-1726 or placebo for four weeks with weekly subcutaneous dosing.
Included an optional four-week extension phase for six participants.
Mean body weight reduction of 6.1% at Day 26 and 9.1% at Day 54 for DA-1726 (p<0.05 vs placebo).
Significant waist circumference reduction of -5.8 cm at Day 22 and -9.8 cm at Day 54 (p<0.05 vs placebo).
Pharmacokinetics supported once-weekly dosing with no serious adverse events reported.

Abstract

Introduction and Objective: DA-1726 is an oxyntomodulin analogue, acting as a dual GLP-1/glucagon receptor agonist. In this first-in-human phase 1 study (NCT06252220), a higher-dose cohort further evaluated the safety, tolerability, pharmacokinetics (PK), and preliminary pharmacodynamics of DA-1726 in obese but otherwise healthy adults. Methods: In this 48 mg multiple-ascending dose cohort, nine patients were randomized in a 6:3 ratio to DA-1726 or placebo (PBO). Participants received once-weekly subcutaneous dosing for four weeks without titration; six entered an optional four-week extension phase at the same dose (four DA-1726; two PBO). Results: In this interim analysis, baseline characteristics in the 48 mg DA-1726 group included mean age of 48.0±12.6 years, body weight 110.4±12.7 kg, and BMI 38.1±3.3 kg/m². During four-weeks of treatment, gastrointestinal (GI) adverse events (AEs) were mainly transient and mild-to-moderate, with no treatment-related discontinuations or serious AEs. PK through Day 50 supported once-weekly dosing with sustained exposure (Cmax 1,397.1±245.0 nM; AUCinf 193,728±29,834 h*nM), terminal half-life of 103.8±20.0 hours, and accumulation ratio of 1.44. Dose-proportional PK with sustained exposure supported weight and anthropometric reductions. In the 48 mg cohort, mean body weight reductions from baseline were 6.1% at Day 26 and 9.1% at Day 54 (p0.05 vs PBO at Day 26), continuing through Week 8 without evidence of plateau. Significant reductions were also observed in waist circumference (−5.8 cm at Day 22; −9.8 cm at Day 54; p0.05 vs PBO) and BMI (−2.3 kg/m² at Day 26; −3.4 kg/m² at Day 54; p0.05 vs PBO at Day 26). Conclusion: DA-1726 was generally well tolerated up to 48 mg, with mainly mild-to-moderate GI AEs and no new safety signals. Clinically meaningful, statistically significant body weight reductions at higher doses were consistent with the dose-proportional PK profile and support continued development for obesity. Disclosure W.C. Fang: Consultant; Current; MetaVia Therapeutics. Y. Chae: None. D. Lee: None. E. Kim: None. R. Homolka: Employee; Ended; MetaVia Inc. J. Lee: Employee; Current; MetaVia Inc. K. Lee: Employee; Current; MetaVia Inc., Dong-A ST Co., Ltd. S. Kim: Employee; Current; MetaVia Inc., Dong-A ST Co., Ltd. M. Kim: None. H. Kim: None.

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Cite This Study

FANG et al. (Fri,) studied this question.

synapsesocial.com/papers/6a250c7d7def13d035e1c984 https://doi.org/https://doi.org/10.2337/db26-3102-lb

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