Is Zenagamtide in Phase 2 Human Trials? What the 2026 Data Actually Show
The concise answer
Yes. Zenagamtide—formerly known as amycretin—has been studied in a phase 2 human trial involving adults with type 2 diabetes. The completed study, NCT06542874, enrolled 448 participants and evaluated both once-daily oral tablets and once-weekly subcutaneous injections. Results were published in two peer-reviewed Lancet papers in 2026: one reporting the oral groups and one reporting the injectable groups.
That does not mean zenagamtide is approved or available for routine clinical use. It remains an investigational compound. The phase 2 findings provide evidence about dose response, blood-glucose changes and safety over 36 weeks in a specific study population; they do not establish long-term outcomes, broad effectiveness or regulatory approval.
What is zenagamtide?
Zenagamtide is the current name for the investigational compound previously called amycretin. It is a single peptide molecule designed to activate GLP-1, amylin and calcitonin receptors. The two 2026 publications describe it as a unimolecular GLP-1 and amylin receptor agonist and identify activity at the calcitonin receptor as well.
Those targets are relevant to metabolic research, but a mechanism is not the same thing as a demonstrated clinical benefit. Receptor activity explains why a compound is being studied; randomized human trials are needed to determine what happens in a defined population under controlled conditions.
Zenagamtide and cagrilintide are different molecules and should not be treated as interchangeable.
Was this one phase 2 trial or two?
It was one registered, multicenter phase 2 study with separate oral and injectable treatment groups. The trial registry lists an actual enrollment of 448 participants. The two Lancet reports divide that population into:
- 186 participants in the once-daily oral analysis; and
- 262 participants in the once-weekly subcutaneous analysis.
Both reports cite the same ClinicalTrials.gov identifier, NCT06542874. Calling them “two phase 2 trials” can therefore be misleading. A more precise description is two peer-reviewed reports from one phase 2 study.
The study was randomized, double-blind, placebo-controlled and dose-finding. It ran at 83 hospital and clinic sites across 11 countries. Participants were adults ages 18 to 75 with type 2 diabetes, an HbA1c of 7.0% to 10.0%, and a BMI from 23.0 to below 50.0 kg/m². They were taking stable metformin, with or without an SGLT2 inhibitor.
The intervention lasted 36 weeks, followed by four weeks of follow-up. The primary outcome for both routes was change in HbA1c from baseline to week 36.
What did the oral zenagamtide groups show?
The oral zenagamtide phase 2 report randomized 186 participants to placebo or one of three once-daily maintenance doses: 6 mg, 25 mg or 50 mg. Dosing began at 1.5 mg and was escalated every four weeks until the assigned maintenance dose was reached.
At week 36, the estimated mean changes in HbA1c from baseline were:
- −0.9 percentage points with 6 mg;
- −1.3 percentage points with 25 mg; and
- −1.4 percentage points with 50 mg.
The estimated differences versus placebo were −0.5, −0.99 and −1.09 percentage points, respectively. Each comparison met the report’s threshold for statistical significance.
These numbers apply to the trial’s specified efficacy analysis: on-treatment data without rescue medication. They should not be converted into a general prediction for an individual or a different population.
Gastrointestinal events were the most common adverse events. They were reported in 26% of the 6 mg group, 41% of the 25 mg group, 47% of the 50 mg group and 23% of the placebo group. Seven serious adverse events were reported across the zenagamtide groups, compared with none in the placebo group. No deaths occurred during the trial.
What did the injectable zenagamtide groups show?
The subcutaneous zenagamtide phase 2 report randomized 262 participants. Of those, 225 were assigned to one of six once-weekly zenagamtide doses—0.4, 1.5, 5, 10, 20 or 40 mg—and 37 were assigned to placebo.
At week 36, estimated mean HbA1c changes ranged from −0.9 percentage points with 0.4 mg to −1.7 percentage points with 40 mg. The corresponding estimated differences versus placebo ranged from −0.77 to −1.56 percentage points.
Most adverse events were gastrointestinal and were described as mild to moderate in severity. Among 261 participants exposed to treatment, 21 reported serious adverse events: 18 across the six zenagamtide groups and three in the placebo group. No deaths occurred.
Novo Nordisk also highlighted weight change as a secondary finding in its ADA 2026 investor presentation, reporting up to 14.6% weight loss in the subcutaneous program. That figure should be read in its full context: it came from a sponsor presentation, was not the primary endpoint summarized in the PubMed abstract, and reflects one dose, analysis approach, study duration and population. It is not a forecast of what another person would experience.
What did the trial establish?
The study established that, in the enrolled type 2 diabetes population, both oral and injectable zenagamtide produced dose-related HbA1c reductions over 36 weeks compared with placebo. It also produced a structured safety dataset large enough to inform later-stage development.
Phase 2 is designed to investigate efficacy signals, dose selection and safety—not to provide the final evidence package for broad approval. The results help answer whether further trials are justified and how those trials might be designed.
What does the trial not establish?
Several limits matter:
- The study lasted 36 weeks, so it does not answer questions about multiyear safety or durability.
- Participants had type 2 diabetes and were taking defined background therapies; the results should not automatically be generalized to people without diabetes.
- The trial was sponsored by Novo Nordisk. The publications disclose that several authors were employees and shareholders of the sponsor and that other authors had industry relationships. Disclosure does not invalidate a study, but it is relevant context.
- The dose groups were relatively small, especially when interpreting uncommon adverse events.
- Phase 2 results do not guarantee phase 3 success or regulatory approval.
- The study did not compare zenagamtide head-to-head with semaglutide, tirzepatide, retatrutide or another active treatment.
The last point is especially important. Cross-trial comparisons can be distorted by different populations, durations, endpoints, estimands, background therapies and dose-escalation schedules.
Is zenagamtide approved?
No approval is established by these reports. ClinicalTrials.gov describes NNC0487-0111—the study code for zenagamtide—as a new medicine that cannot be prescribed and lists the phase 2 study as completed. The registry and 2026 publications describe an investigational program; publication in a peer-reviewed journal does not itself change regulatory status. Because status can change, readers should verify it through current regulator databases rather than relying on social posts or old articles.
Frequently asked questions
Are amycretin and zenagamtide the same compound?
Yes. The 2026 peer-reviewed reports state that zenagamtide was formerly known as amycretin. Zenagamtide is the current name used in the publications.
Was zenagamtide tested in humans?
Yes. NCT06542874 was a randomized phase 2 human study enrolling 448 adults with type 2 diabetes. The oral and injectable groups were reported separately.
Was an oral version tested?
Yes. The study tested once-daily oral doses of 6, 25 and 50 mg, as well as once-weekly subcutaneous doses from 0.4 to 40 mg.
Does phase 2 mean the compound is proven safe and effective?
No. Phase 2 provides controlled evidence about efficacy signals, dose response and safety over a limited period in a defined population. Larger and longer studies are generally needed to support broader conclusions and any regulatory application.
Can these results be compared directly with other metabolic compounds?
Not reliably from headline percentages alone. A valid comparison would need to account for study population, comparator, duration, outcome definition, estimand, dose escalation and missing-data handling.
The bottom line
Zenagamtide has reached phase 2 human research, and the completed 448-participant study produced peer-reviewed oral and injectable results. Both routes reduced HbA1c compared with placebo over 36 weeks in adults with type 2 diabetes, while gastrointestinal adverse events were common and serious adverse events occurred in both active-treatment and placebo groups in the injectable analysis.
The accurate takeaway is promising but limited: zenagamtide generated a phase 2 signal worth studying further. It is not the same as FDA approval, proof of long-term safety or evidence that headline outcomes apply to everyone.
Explore the JD BioWorks Research Library for source-linked explanations of peptide studies, analytical methods and regulatory developments.
Sources
- Mora P, et al. Efficacy and safety of once-daily oral zenagamtide in adults with type 2 diabetes: a phase 2 trial. The Lancet. 2026;408(10555):607–620. doi:10.1016/S0140-6736(26)01247-X.
- Mora P, et al. Efficacy and safety of once-weekly subcutaneous zenagamtide in type 2 diabetes: a phase 2 trial. The Lancet. 2026;408(10555):621–635. doi:10.1016/S0140-6736(26)01248-1.
- ClinicalTrials.gov. NCT06542874: Safety and efficacy of subcutaneous and oral NNC0487-0111 in participants with type 2 diabetes. Record updated August 13, 2026.
- Novo Nordisk. R&D investor presentation, ADA 2026.
Research-use and medical disclaimer: This article summarizes published research for educational purposes. It is not medical advice, treatment guidance or a recommendation to use an investigational compound. JD BioWorks materials are intended for qualified laboratory research only and are not for human or veterinary use.