Peptide education
Amycretin
Zenagamtide · NNC0487-0111
Amycretin, also called zenagamtide, is an investigational peptide designed to activate GLP-1 and amylin receptors. Researchers have studied it as a daily oral medicine and a weekly injection for weight or blood-sugar outcomes.
Early trials found weight loss and improvements in blood sugar in different groups of participants. Amycretin remains investigational in the United States.
Overview
Quick answer
The large weight-change figure often associated with amycretin came from a small injection study, not the oral diabetes trial. The two routes have different dose levels, schedules, study populations, and endpoints.
Is amycretin the same as zenagamtide?
Yes. Zenagamtide is the newer name used in the diabetes publication for the compound previously called amycretin.
Is amycretin FDA-approved?
No FDA-approved product under either name was found in the FDA drug database. The developer describes zenagamtide as investigational. Approval in another country requires a separate regulator check.
What did the injection study find?
In one part of a small study, participants receiving weekly injections escalated to 60 mg had an estimated mean weight change of minus 24.3% at week 36, versus minus 1.1% in that part's placebo group. That part assigned 17 participants to amycretin and five to placebo. Seven of the 17 completed the study; six withdrew because of adverse events.
What did the oral diabetes trial measure?
The phase 2 trial tested daily oral doses in adults with type 2 diabetes already taking metformin, with or without an SGLT2 inhibitor. Each active group had a greater estimated reduction in HbA1c than placebo at 36 weeks.
Is the phase 3 trial a completed result?
No. AMAZE 1 studies a weekly injection and AMAZE 9 studies daily tablets in adults with obesity without diabetes. AMBITION 7 studies the injection in a different population with type 2 diabetes and increased cardiovascular risk. The registries list all three as recruiting, without completed efficacy results.
Evidence
Evidence snapshot
A single-center trial randomized 125 adults across several study parts. The 60 mg result belongs to one escalating-dose part with 17 active participants and five placebo participants. Six of 17 active participants withdrew because of adverse events.
A 186-person trial reported reductions in HbA1c versus placebo across three daily dose groups. Participants had type 2 diabetes and received background treatment.
Separate registered phase 3 studies include oral and injection obesity trials, plus an injection trial in adults with type 2 diabetes and increased cardiovascular risk. Registrations describe study plans.
The oral and injection reports describe gastrointestinal events. The studies are too limited to settle rare or long-term risks.
Claims
Common claims vs evidence
| Claim | Human evidence | Mechanistic evidence | Verdict |
|---|---|---|---|
| Amycretin caused large weight changes in an early injection trial. | The 60 mg dose-escalation part estimated a mean weight change of minus 24.3% at 36 weeks, versus minus 1.1% for its placebo group. Other study parts used different doses and durations. The 60 mg part assigned 17 participants to amycretin and five to placebo. | GLP-1 and amylin receptor activity explains the research interest, but the trial outcome is more informative than the proposed mechanism. | Supported for that small study part, with substantial withdrawal and limited follow-up. It is not a predicted result for an individual. |
| The same numbers apply to the oral formulation. | The published oral studies used different schedules. One was a first-in-human study in adults with overweight or obesity; another was a 36-week phase 2 trial in adults with type 2 diabetes. | No. The 60 mg injection result should not be assigned to an oral tablet or to a different study population. | |
| Amycretin is the same medicine as semaglutide or CagriSema. | Amycretin is a single investigational molecule. The FDA drug database search did not find an approved amycretin or zenagamtide product. | No. Similar pathway names do not make separate compounds, combinations, or their regulatory decisions interchangeable. |
Bottom line
Main takeaway
The tablet and injection are being studied separately. A headline result from one does not tell you what the other will do.
The early injection trial studied adults with overweight or obesity; the oral phase 2 trial studied adults with type 2 diabetes on background treatment. Their outcomes answer different questions.
Published early-phase trials report outcomes and adverse events. The phase 3 registry describes a planned study, not a completed result.
Identity
What it is
Amycretin is a single peptide acting at GLP-1 and amylin receptors. It is distinct from giving separate medicines that target these pathways.
Researchers have tested an oral form taken once daily and a subcutaneous form studied once weekly. Both remain research formulations in the U.S.
Use context
Routes, doses, and cycle patterns
Oral and injection studies used different formulations and schedules. The early injection weight study and the diabetes cohorts enrolled different groups. Neither route has an FDA-approved amycretin product.
Human studies and product labels
Injection dose-escalation study
- Purpose
- Safety and weight outcomes
- Context
- Phase 1b/2a trial in adults with overweight or obesity
- Route
- Subcutaneous
- Amount
- Escalated from 0.3 mg to 60 mg in one study part
- Frequency
- Once weekly
- Duration
- 36 weeks in that part
The comparison was with the placebo group in the same trial part. Six of the 17 participants assigned to amycretin withdrew because of adverse events, and seven completed the study.
Oral diabetes study
- Purpose
- Glycemic outcomes
- Context
- Phase 2 trial in adults with type 2 diabetes on background treatment
- Route
- Oral
- Amount
- Started at 1.5 mg and escalated every four weeks to 6 mg, 25 mg, or 50 mg
- Frequency
- Once daily
- Duration
- 36 weeks
The primary comparison was change in HbA1c against placebo. These are trial groups, not approved or interchangeable injection doses. A published correction states that the 25 mg and 50 mg groups spent 20 and 16 weeks, respectively, at their maintenance doses.
Injection diabetes study
- Purpose
- Glycemic outcomes
- Context
- Separate injection cohort of the phase 2 diabetes trial
- Route
- Subcutaneous
- Amount
- Started at 0.2 mg and escalated every four weeks to 0.4, 1.5, 5, 10, 20, or 40 mg
- Frequency
- Once weekly
- Duration
- 36 weeks
These are study targets, not approved doses. The injection and oral diabetes cohorts share a trial registration but report separate results.
First-in-human oral study
- Purpose
- Safety, drug exposure, and exploratory weight outcomes
- Context
- Multipart phase 1 trial in adults with overweight or obesity
- Route
- Oral
- Amount
- Escalating groups included 50 mg and 100 mg daily targets
- Frequency
- Once daily in the multiple-dose groups
- Duration
- 12 weeks in the longer multiple-dose parts
The 100 mg group received two 50 mg tablets as a single daily dose.
What varies
- Route: an oral tablet and an injection are different study formulations.
- Population: weight-only and type 2 diabetes trials enrolled different groups.
- Status: phase 3 registration does not mean the drug has been approved.
Research
Research evidence
The injection phase 1b/2a trial reported substantial estimated weight reductions but also substantial withdrawal. A separate first-in-human oral study assessed safety and drug exposure, with weight as an exploratory outcome. Separate oral and injection cohorts in a phase 2 diabetes trial measured HbA1c over 36 weeks. Those results should not be merged.
| Study / evidence area | Population | Design | Product context | Main outcome | Limitations | Weight |
|---|---|---|---|---|---|---|
| Subcutaneous phase 1b/2a | 125 adults with overweight or obesity across five study parts | Randomized, placebo-controlled, single-center trial | Once-weekly injection with several escalation and maintenance arms | In the 60 mg escalation part, estimated mean weight change at week 36 was minus 24.3%, versus minus 1.1% in its placebo group. | Safety was the primary endpoint; withdrawal was substantial and the 60 mg part assigned 17 participants to amycretin and five to placebo. Seven of the 17 completed the study; six withdrew because of adverse events. | Early controlled human evidence |
| First-in-human oral phase 1 | 144 adults with overweight or obesity across multiple study parts | Randomized, double-blind, placebo-controlled trial | Single or multiple oral doses, depending on study part | The researchers assessed adverse events and drug exposure; weight change was exploratory in the longer oral-dose parts. | The study was small and short. Oral results should not be substituted for injection results. | Early human safety and exposure data |
| Oral phase 2 diabetes trial | 186 adults with type 2 diabetes on metformin, with or without an SGLT2 inhibitor | Multicenter, randomized, double-blind, placebo-controlled trial | Daily oral zenagamtide at three dose levels | At week 36 the estimated HbA1c differences versus placebo were minus 0.5, minus 0.99, and minus 1.09 percentage points for 6, 25, and 50 mg. | The primary analysis used on-treatment data without rescue medication. Long-term safety in broader populations remains uncertain. | Controlled phase 2 human evidence |
| Injection phase 2 diabetes cohort | 262 randomized adults with type 2 diabetes on metformin, with or without an SGLT2 inhibitor | Multicenter, randomized, masked, placebo-controlled phase 2 trial | Weekly injections escalated to six separate target doses | At week 36, estimated HbA1c change ranged from minus 0.9 percentage points at 0.4 mg to minus 1.7 at 40 mg. Estimated differences versus placebo ranged from minus 0.77 to minus 1.56 percentage points. | The primary efficacy estimand used on-treatment data without rescue medication. This cohort shares a registration with the oral cohort but has separate dosing and results. | Controlled phase 2 human evidence |
| AMAZE 1 | Adults with obesity, excluding people with a history of diabetes | Registered phase 3 randomized placebo-controlled study | Once-weekly subcutaneous investigational treatment | The registry describes a recruiting study, not completed outcome data. | Results and regulatory review are not established by registration. | Trial registry, not efficacy results |
| AMAZE 9 and AMBITION 7 | Separate obesity without diabetes and type 2 diabetes with increased cardiovascular risk populations | Registered randomized phase 3 studies | Daily oral tablet in AMAZE 9; weekly injection versus daily insulin glargine in AMBITION 7 | Both registries describe recruiting studies without completed efficacy results. | Recruitment status can change; the studies enroll different populations and use different comparators. | Trial registries, not efficacy results |
Cautions
Safety and unknowns
- Gastrointestinal events were the most common events in the injection study. Most were mild or moderate, but the study also had a large number of withdrawals, including for reasons unrelated to adverse events. In the 60 mg part, six of 17 amycretin participants withdrew because of adverse events, compared with none of five placebo participants.
- In the oral diabetes trial, gastrointestinal events occurred in 26%, 41%, and 47% of the 6 mg, 25 mg, and 50 mg groups, versus 23% with placebo. Seven treated participants had serious adverse events and none did in the placebo group; occurrence alone does not establish that the drug caused each event.
- In the separate injection diabetes cohort, 21 of 261 treated participants reported serious adverse events: 18 received zenagamtide and three received placebo. The report does not establish that each event was caused by the study drug.
- The oral first-in-human study reported mild or moderate treatment-emergent events and frequent gastrointestinal events. Small early studies cannot reliably rule out uncommon harms or establish long-term safety.
Product quality
Product identity and quality
The studies used controlled research material. A label on an independently obtained product does not verify its identity, concentration, formulation, or handling.
Approval and formulation
A U.S. FDA-approved amycretin product was not found in the drug database. The oral and injectable research formulations are distinct.
Product identity
Trial results describe the study drug, not the contents or sterility of an unrelated product bearing the same name.
Mechanism
How it is proposed to work
Amycretin is designed to activate receptors for GLP-1 and amylin, two signaling pathways relevant to appetite and metabolic regulation.
The diabetes publication also describes activity at calcitonin receptors. Receptor activity is a description of the molecule, not proof of a better clinical outcome than another drug.
Clinical outcomes depend on formulation, dose, population, and study design; they cannot be inferred from the number of receptor targets.
FAQ
Common questions
Is amycretin FDA-approved?
No FDA-approved amycretin or zenagamtide product was found in the FDA drug database. The developer describes it as investigational.
Are oral and injectable amycretin the same regimen?
No. They are formulations of the same investigational molecule studied with different routes, schedules, and dose levels.
Details
Technical details
Sources
References
- 1.
doi:10.1016/S0140-6736(25)01176-6 PMID:40550229 NCT05369390
First-in-human oral phase 1 trial; the weight outcomes were exploratory.
- 2.
PubMed. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously
doi:10.1016/S0140-6736(25)01185-7 PMID:40550231 NCT06064006
Randomized injection trial in adults with overweight or obesity at one U.S. center; withdrawal was substantial.
- 3.
Novo Nordisk investor presentation. Phase 1b/2a amycretin trial results presentation
NCT06064006
Sponsor presentation reports treatment-group sizes and the percentage with adverse events leading to withdrawal.
- 4.
The Lancet supplementary appendix. Supplement to the phase 1b/2a amycretin trial
NCT06064006
Table S5 lists individual discontinuations and their reported reasons by study part.
- 5.
PubMed. Efficacy and safety of once-daily oral zenagamtide in adults with type 2 diabetes
doi:10.1016/S0140-6736(26)01247-X PMID:42532079 NCT06542874
Randomized oral phase 2 diabetes trial; zenagamtide is the newer name for amycretin.
- 6.
PubMed. Published correction to the oral zenagamtide phase 2 trial
doi:10.1016/S0140-6736(26)02107-0 PMID:42913681
Published correction to the discussion's maintenance-dose duration for the 25 mg and 50 mg oral groups.
- 7.
PubMed. Efficacy and safety of once-weekly subcutaneous zenagamtide in type 2 diabetes
doi:10.1016/S0140-6736(26)01248-1 PMID:42532080 NCT06542874
Published phase 2 injection cohort from the same registered study as the oral diabetes cohort.
- 8.
ClinicalTrials.gov. AMAZE 1: efficacy and safety of once-weekly subcutaneous NNC0487-0111 in participants with obesity
NCT07339423
Phase 3 registry describes the planned design, eligibility, and recruiting status, not completed outcomes.
- 9.
ClinicalTrials.gov. AMAZE 9: efficacy and safety of once-daily oral zenagamtide in participants with obesity
NCT07720271
Phase 3 oral obesity trial registry; excludes prior diabetes and reports recruiting, not completed results.
- 10.
ClinicalTrials.gov. AMBITION 7: zenagamtide versus insulin glargine in type 2 diabetes
NCT07797335
Phase 3 registry for a weekly injection compared with daily insulin glargine in adults with type 2 diabetes and increased cardiovascular risk.
- 11.
Novo Nordisk. Novo Nordisk phase 2 zenagamtide update
Developer identifies zenagamtide as investigational and also called amycretin; this sponsor update is separate from the published diabetes cohorts.
- 12.
FDA. Drugs@FDA: FDA-approved drugs database
A Drugs@FDA API active-ingredient search returned no matches for amycretin or zenagamtide; the developer describes it as investigational.