DA-1726 Early Results: Dual-Action Peptide for Obesity & MASH

Featured snippet (40–60 words): Early Phase 1 results presented at the 2026 American Diabetes Association meeting show that once-weekly DA-1726, a glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist, cut body weight by 9.1 % in eight weeks with mostly mild gastrointestinal side effects, highlighting potential for obesity and metabolic dysfunction–associated steatohepatitis (MASH) treatment.(diabetesjournals.org)

Last updated August 2026

What Is DA-1726 and How Does It Work?

DA-1726 is a synthetic analogue of oxyntomodulin, a naturally occurring gut hormone that activates both the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). By stimulating GLP-1R, the drug curbs appetite and slows stomach emptying; simultaneous GCGR activation boosts energy expenditure, helping you burn more calories at rest.(diabetesjournals.org)

Although early press coverage referred to DA-1726 as a dual amylin/calcitonin agent, peer-reviewed data clarify that its primary targets are GLP-1R and GCGR. The multi-receptor approach is designed to match or exceed the weight-loss potency of tirzepatide and survodutide while avoiding dose-limiting nausea.(diabetesjournals.org)

What Did the Phase 1 Trial Show About Safety?

The ongoing first-in-human study (NCT06252220) enrolled adults aged 18-65 years with body-mass index (BMI) 30-45 kg/m². Participants received once-weekly subcutaneous injections of DA-1726 (up to 48 mg) or placebo for eight weeks without dose titration.(clinicaltrials.gov)

Key safety findings:

• No study drug–related serious adverse events (SAEs) observed.(diabetesjournals.org)
• The most frequent adverse events were nausea (44 %), diarrhea (33 %), and transient vomiting (22 %). Most events were mild or moderate and resolved within 48 hours.
• No clinically meaningful hypoglycemia occurred in non-diabetic subjects.
• Laboratory parameters, vital signs, and electrocardiograms remained within normal limits.

Table 1. Treatment-Emergent Adverse Events Through Day 54

Event	DA-1726 48 mg (n=6)	Placebo (n=3)
Nausea	3 (50 %)	0 (0 %)
Diarrhea	2 (33 %)	0 (0 %)
Vomiting	1 (17 %)	0 (0 %)
Injection-site pain	1 (17 %)	0 (0 %)
Serious AEs	0 (0 %)	0 (0 %)

Overall, the short study duration limits conclusions on rare events, but the benign profile supports continued development.

How Much Weight Loss Did Participants Experience?

DA-1726 produced rapid, progressive weight and waist-line reductions:

Table 2. Efficacy Outcomes in the 48 mg Cohort

Outcome	Baseline	Day 26	Day 54
Body weight (kg)	110.4 ± 12.7	−6.1 %	−9.1 %
Waist circumference (cm)	118.6 ± 8.4	−5.8	−9.8
BMI (kg/m²)	38.1 ± 3.3	−2.3	−3.4

The 9.1 % mean weight loss over eight weeks rivals the 12-week reductions seen with tirzepatide dose-escalation, suggesting that DA-1726’s energy-expenditure boost may allow faster results without titration.

How Might DA-1726 Benefit Metabolic Dysfunction–Associated Steatohepatitis (MASH)?

Preclinical studies in diet-induced NASH (now called MASH) mice found that DA-1726 reduced hepatic fat by up to 43 % and improved plasma lipids more than semaglutide.(diabetesjournals.org) The peptide decreased alanine aminotransferase (ALT) and fibrosis markers, hinting at direct liver benefits beyond weight loss.

The molecule’s glucagon activity may promote hepatic lipid oxidation, while GLP-1 signaling improves insulin sensitivity — two mechanisms believed to slow MASH progression. Human biopsy data will be needed to confirm these effects.

How Does DA-1726 Compare With Other Peptide Drugs?

In animal models, DA-1726 matched or exceeded the weight-loss efficacy of several market-leading or late-stage peptides:

• Semaglutide (GLP-1RA): DA-1726 achieved −17.2 % vs −12.9 % weight change in DIO mice at equimolar doses.(diabetesjournals.org)
• Tirzepatide (GLP-1/GIP dual): Both agents showed ~31 % maximal weight loss, but DA-1726 allowed higher food intake, indicating increased energy expenditure.(diabetesjournals.org)
• Survodutide (GLP-1/GCGR dual): DA-1726 produced similar weight loss while lowering total cholesterol and triglycerides more deeply.(diabetesjournals.org)

The table below summarizes available head-to-head preclinical metrics.

Table 3. Comparative Preclinical Efficacy (Diet-Induced Obese Mice)

Peptide	Mechanism	Weight Change	Total Cholesterol	Food Intake vs Control
DA-1726	GLP-1/GCGR	−31.9 %	−67.7 %	90–95 %
Semaglutide	GLP-1	−25.4 %	−41 %	70–80 %
Tirzepatide	GLP-1/GIP	−31.3 %	N/A	66–72 %
Survodutide	GLP-1/GCGR	−25.4 %	−49.6 %	85–90 %

These data suggest DA-1726 may combine robust weight loss with lipid benefits, an attractive profile for patients with obesity-associated dyslipidemia.

What Are the Potential Side Effects and Risks?

Because DA-1726 activates GLP-1R, it shares the class’s expected gastrointestinal side effects. In the Phase 1 study, nausea and diarrhea predominated, were dose-dependent, and generally resolved within two days.(diabetesjournals.org)

Potential risks to monitor as doses escalate include:

• Pancreatitis: No cases reported so far, but monitoring is standard for incretin-based therapies.
• Gallbladder disease: Rapid weight loss can precipitate gallstones.
• Cardiovascular effects: Preclinical data show neutral blood pressure impact, but human data are limited.
• Lean-mass loss: Dual agonists that boost energy expenditure can erode muscle unless protein intake and resistance exercise are adequate.

What Comes Next in Clinical Development?

The sponsor has initiated Part 3 of the Phase 1 program to evaluate higher single doses and a 12-week multiple-dose titration scheme. Top-line results are expected in late 2026. A Phase 2 randomized study in 300 adults with obesity and MASH is planned for early 2027 pending regulatory feedback.(ir.metaviatx.com)

Key objectives for future trials include:

• Confirming ≥15 % weight-loss durability at 24–48 weeks
• Assessing liver histology improvements in biopsy-confirmed MASH
• Comparing DA-1726 head-to-head with semaglutide and tirzepatide
• Exploring combination therapy with GPR119 agonist vanoglipel

When to Contact Your Healthcare Provider

• Severe or persistent abdominal pain radiating to the back (possible pancreatitis)
• Yellowing of skin or eyes, dark urine, or light-colored stools (possible liver injury)
• Repeated vomiting or inability to keep fluids down for >24 hours
• Signs of gallbladder attack: sudden right-upper-quadrant pain, fever, or chills
• Rapid heartbeat, dizziness, or fainting after an injection

Scientific References

1. Fang W et al. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DA-1726, an Oxyntomodulin Analogue: Phase 1 Higher-Dose Cohort Results. Diabetes. 2026;75(Supplement 1):3102-LB.(diabetesjournals.org)
2. ClinicalTrials.gov. NCT06252220: A Phase 1 First-in-Human Study of DA-1726 in Adults With Obesity. Updated April 2026.(clinicaltrials.gov)
3. Chae Y et al. Therapeutic Potential of DA-1726, a Novel Oxyntomodulin Analogue, in a Diet-Induced NASH Mouse Model. Diabetes. 2022;71(Supplement 1):1333-P.(diabetesjournals.org)
4. Pereira M et al. Differentiated Metabolic Effects of DA-1726, a Balanced GLP1R/GCGR Dual Agonist. Diabetes. 2023;72(Supplement 1):1668-P.(diabetesjournals.org)
5. Park S et al. DA-1726, a GLP1R/GCGR Dual Agonist, a Promising Approach in Obesity Treatment and Lipid Management. Diabetes. 2024;73(Supplement 1):2058-LB.(diabetesjournals.org)
6. Tilbrook AJ et al. Development of a Long-Acting Stapled Dual Amylin and Calcitonin Receptor Agonist for Obesity. Bioconjug Chem. 2026;37(1):169-179.(pubs.acs.org)