Zenagamtide Phase 2 Results: Amycretin’s Oral and Weekly Forms Enter a New Stage

Zenagamtide phase 2 results provide a new peer-reviewed update on the investigational compound formerly known as amycretin. Two randomized phase 2 trials published in The Lancet on August 15, 2026, evaluated separate oral and once-weekly subcutaneous formulations in adults with type 2 diabetes. Both studies reported glucose-lowering activity and gastrointestinal adverse events as the most common safety findings. The results support continued research, but they do not establish FDA approval, superiority over approved medicines, or a recommended treatment use.

The update is important because it adds published clinical evidence to a program that had previously been discussed mainly through early development and pipeline reporting. Zenagamtide is a single investigational molecule designed to engage <a href="https://glp1place.com/tools/compound/glp-1/”>GLP-1, amylin, and calcitonin-receptor-related signaling. The program now includes both a daily oral formulation and a weekly injectable formulation, while a phase 3 obesity study is being prepared to compare weekly zenagamtide with semaglutide.

For readers of GLP1Place’s earlier coverage of amycretin’s initial phase 2 development, the central change is that the compound is now being reported under the name zenagamtide, with peer-reviewed dose-finding and safety data available for both formulations.

What the new zenagamtide phase 2 results show

The oral and weekly studies were separate randomized, double-blind, placebo-controlled phase 2 trials. They were not a head-to-head comparison between formulations, and neither was a definitive obesity registration study. Their objectives included evaluating dose response, glycemic control, tolerability, and the feasibility of continuing development.

The weekly trial randomized 262 participants. Of these, 225 were assigned to zenagamtide and 37 to placebo. At week 36, estimated HbA1c reductions across the zenagamtide dose groups ranged from 0.9 percentage points at 0.4 mg to 1.7 percentage points at 40 mg. Relative to placebo, the reported treatment differences ranged from 0.77 to 1.56 percentage points, with statistically significant findings across the dose groups reported by the investigators.

The weekly study also provides a preliminary safety context. Among 261 participants included in the safety analysis, 21 reported serious adverse events. These events occurred among participants in both the zenagamtide and placebo groups, and no deaths occurred. The investigators described most adverse events as gastrointestinal and mild to moderate. These findings require interpretation within the limits of a 36-week phase 2 trial and do not define the complete long-term safety profile.

The weekly-study report is available through its PubMed record. The separate oral-study report is indexed at the corresponding PubMed record.

The oral trial evaluated once-daily zenagamtide at 6, 25, and 50 mg in adults with type 2 diabetes. Its significance is not simply that the compound was placed in a tablet. Oral delivery introduces a separate development question: whether a peptide-based metabolic mechanism can be delivered by mouth with adequate exposure, acceptable tolerability, and a dosing routine that can be evaluated in larger studies.

The oral and weekly numbers should not be compared by milligrams alone. A 50 mg oral maintenance dose is not inherently stronger or weaker than a 40 mg weekly dose. Absorption, bioavailability, exposure over time, formulation characteristics, receptor activity, and dose-escalation design all influence the clinical result. Cross-trial comparisons are especially uncertain when the studies use different populations, schedules, and statistical estimands.

Why zenagamtide’s mechanism matters

Zenagamtide was previously known as amycretin and carries the research identifier NNC0487-0111. Published descriptions characterize it as a unimolecular agonist involving the GLP-1, amylin, and calcitonin receptor systems. The intended rationale is to combine complementary metabolic signals in one molecule rather than relying on GLP-1 activity alone.

GLP-1 signaling

GLP-1 receptor signaling can support glucose-dependent insulin secretion, reduce glucagon release in relevant physiological settings, slow gastric emptying, and influence appetite-related neural pathways. Semaglutide is a selective GLP-1 receptor agonist used as a benchmark in current metabolic-drug research. GLP1Place’s GLP-1 receptor research overview provides additional background on this pathway.

Amylin signaling

Amylin is co-secreted with insulin by pancreatic beta cells. It contributes to post-meal satiety, gastric-emptying control, and regulation of nutrient flow. Amylin biology is also being studied through separate compounds such as cagrilintide and combination programs such as CagriSema. Those programs should not be assumed to have the same structure, pharmacology, or clinical profile as zenagamtide.

Calcitonin-receptor-related activity

Amylin-receptor biology involves the calcitonin receptor and receptor activity-modifying proteins. The presence of calcitonin-receptor-related activity in zenagamtide’s design does not mean that zenagamtide is the same as calcitonin. It also does not support conclusions about bone or mineral metabolism beyond outcomes directly assessed in clinical research.

The scientific question is whether these signals provide useful complementarity in humans. A mechanistic rationale is not proof of clinical benefit. Future trials must establish how the combined activity affects HbA1c, body weight, body composition, treatment persistence, adverse events, and longer-term outcomes.

Oral versus weekly zenagamtide

The two phase 2 studies show that both formulations have progressed far enough to justify further investigation. They do not establish that one formulation is more effective, safer, or more convenient than the other.

The oral formulation could eventually address preferences and practical barriers associated with injections, but a daily schedule can create its own adherence demands. Oral peptide formulations also require formulation strategies that can produce adequate and consistent exposure. The phase 2 report does not establish how oral zenagamtide will compare with approved oral GLP-1 therapy or with weekly injectable treatments in people with obesity.

The weekly formulation uses a schedule familiar from current incretin research. Fewer administration events may be relevant to treatment persistence, but weekly dosing does not remove the need for clinical supervision, dose escalation, safety monitoring, or follow-up. The study does not demonstrate greater weight loss than semaglutide, tirzepatide, mazdutide, or other investigational medicines.

Both phase 2 trials enrolled adults with type 2 diabetes. That matters when interpreting future obesity claims. Diabetes and obesity-only populations can differ in baseline weight, glucose status, background medication, comorbidity burden, and treatment response. An obesity development program will need to evaluate percentage weight change, weight-maintenance effects, categorical response thresholds, body composition, metabolic outcomes, and discontinuation rates.

How the findings fit the metabolic pipeline

Zenagamtide is entering a competitive field. Semaglutide established a benchmark for selective GLP-1 therapy, while tirzepatide demonstrated the clinical importance of dual GLP-1 and GIP receptor activity. Other investigational programs are exploring glucagon-containing combinations, additional amylin biology, oral delivery, and multi-receptor molecules.

That context makes zenagamtide’s design scientifically notable but raises the evidence standard. A new receptor combination is not automatically superior. Its clinical value will depend on the balance among efficacy, tolerability, dosing convenience, manufacturing feasibility, durability, and outcomes beyond body weight.

GLP1Place’s coverage of U.S. mazdutide phase 2 results and survodutide phase 3 obesity data concerns different molecules and should not be interpreted as a direct comparison with zenagamtide.

Phase 3 is the next major test

ClinicalTrials.gov lists AMAZE 7, a phase 3 obesity study designed to compare once-weekly zenagamtide with semaglutide. The registry lists an estimated start date of September 22, 2026, estimated enrollment of 650 participants, and estimated completion in October 2028.

The registered design uses matching placebo arrangements so that participants can receive one active treatment and a placebo matched to the other treatment. This type of design is intended to preserve blinding while allowing a direct comparison between active weekly therapies. The registry can be reviewed at ClinicalTrials.gov record NCT07668414.

Important phase 3 questions include:

• Weight-loss magnitude: How does the change in body weight compare with semaglutide under the same trial conditions?
• Response distribution: What proportion of participants reaches clinically meaningful weight-loss thresholds?
• Tolerability: How frequently do gastrointestinal events lead to interruptions or discontinuation?
• Durability: Are effects maintained during longer follow-up?
• Body composition: What happens to fat mass, lean mass, and relevant functional measures?
• Metabolic outcomes: How do HbA1c, fasting glucose, lipids, blood pressure, and other prespecified measures change?

Results from a direct comparison will be more informative than cross-trial rankings because obesity studies can differ substantially in enrollment criteria, dose-escalation schedules, duration, background care, and statistical methods.

Regulatory and safety context

Zenagamtide remains investigational. Peer-reviewed phase 2 publications document clinical research; they do not constitute FDA approval. They also do not establish that any product outside the trial contains the same identity, concentration, purity, sterility, stability, or manufacturing quality as the study material.

The dose levels and schedules in this article are reported research-protocol details. They are not prescribing instructions or guidance for self-administration. Investigational products may be supplied, escalated, monitored, and discontinued under controlled conditions that cannot be reproduced outside a clinical trial.

Readers should distinguish the named investigational compound from unapproved products that may use similar terminology. GLP1Place’s coverage of the FDA GLP-1 active pharmaceutical ingredient import alert discusses why identity, documentation, and quality controls are separate issues from a molecule’s published mechanism.

What remains uncertain

The current evidence is encouraging for continued development but insufficient for a final judgment about clinical value. The weekly study provides dose-response information for HbA1c in type 2 diabetes. The oral study shows that daily oral development is feasible enough to continue. Neither study answers whether zenagamtide will produce durable, clinically meaningful weight loss in obesity or how its overall benefit-risk profile will compare with approved alternatives.

Gastrointestinal tolerability is an especially important open question. Mild-to-moderate events in a phase 2 report do not predict every outcome in larger or longer studies. Discontinuations, dose interruptions, serious adverse events, and patient-reported treatment burden will all matter in phase 3.

Direct comparative evidence will also be needed. The fact that zenagamtide engages three receptor systems does not itself establish superiority over semaglutide, tirzepatide, or other medicines. A differentiated place in therapy could instead depend on a combination of efficacy, persistence, formulation, safety, and metabolic effects.

Researcher takeaways

• Zenagamtide is the current development name for the compound formerly known as amycretin, also identified as NNC0487-0111.
• Two phase 2 trials published on August 15, 2026, evaluated oral and once-weekly formulations in adults with type 2 diabetes.
• The weekly study reported estimated HbA1c reductions of 0.9 to 1.7 percentage points across the reported dose groups at week 36.
• Most adverse events were gastrointestinal and generally mild to moderate in the reported study population.
• Oral and weekly dose levels should not be compared by milligrams alone.
• AMAZE 7 is a registered phase 3 obesity study designed to compare weekly zenagamtide with semaglutide.
• The evidence supports continued investigation but does not establish approval, superiority, or a treatment recommendation.

FAQ: Zenagamtide Phase 2 Results

What are the new zenagamtide phase 2 results?

Two peer-reviewed phase 2 trials published in The Lancet on August 15, 2026, evaluated zenagamtide in adults with type 2 diabetes. One studied once-daily oral treatment and the other once-weekly subcutaneous treatment. Both reported glucose-lowering activity, with gastrointestinal events among the most common adverse events.

Is zenagamtide the same drug as amycretin?

Zenagamtide is the current development name for the compound previously known as amycretin. Its research identifier is NNC0487-0111. Published descriptions characterize it as a single molecule designed to engage GLP-1, amylin, and calcitonin-receptor-related signaling.

Is zenagamtide approved by the FDA?

No. Zenagamtide remains investigational and has not been approved by the FDA. Phase 2 findings do not establish regulatory approval, clinical superiority, or a recommended use.

Was zenagamtide studied as a pill or an injection?

Both formulations were studied in separate phase 2 trials. One used once-daily oral administration, while the other used once-weekly subcutaneous administration.

How does zenagamtide differ from semaglutide and tirzepatide?

Semaglutide is a selective GLP-1 receptor agonist, and tirzepatide activates GLP-1 and GIP receptors. Zenagamtide is designed as one molecule involving GLP-1, amylin, and calcitonin-receptor-related signaling. Direct comparative obesity data remain pending.

What were the main safety findings?

Gastrointestinal events were the most common reported adverse events and were generally described as mild to moderate. In the weekly study, 21 of 261 participants included in the safety analysis reported serious adverse events, and no deaths occurred. Larger and longer studies are needed to define the full safety profile.

Has zenagamtide entered phase 3?

The program has advanced into phase 3 development. AMAZE 7 is a registered obesity study designed to compare weekly zenagamtide with semaglutide, with an estimated start date of September 22, 2026.

Bottom line: The August 15, 2026 zenagamtide phase 2 results are the strongest peer-reviewed clinical update yet for the former amycretin program. Oral and weekly formulations showed glucose-lowering activity in type 2 diabetes, but phase 3 comparative efficacy, tolerability, durability, and regulatory review will determine the compound’s eventual role.