Amycretin

updated

Amycretin, now named zenagamtide, is an investigational Novo Nordisk peptide that activates GLP-1 and amylin receptors, given by mouth or by injection in studies. In a phase 1b/2a trial in 125 adults with overweight or obesity, estimated mean weight change at 60 mg was -24.3% versus -1.1% on placebo at week 36, with a large number of withdrawals and no count given. No FDA record or label turned up on 10 October 2026, and no phase 3 result exists.

GLP-1 and amylin receptor co-agonist peptide

  • Zenagamtide (WHO Proposed INN List 133, 2025) is the new name for amycretin: a human GLP-1(7-37) variant fused through a G4 linker to an artificial amylin receptor agonist, with a fatty diacid side chain on lysine 31 (C343H550N94O116, CAS 3005889-81-3).
  • In a phase 1b/2a subcutaneous trial in 125 adults with overweight or obesity, estimated mean weight change was -24.3% at 60 mg versus -1.1% on placebo at week 36; the abstract says a large number of participants withdrew and gives no count.
  • Two randomized phase 2 trials in type 2 diabetes (262 subcutaneous, 186 oral) gave estimated HbA1c changes of up to -1.7% (40 mg subcutaneous) and -1.4% (50 mg oral) at week 36.
  • The company reported on 25 November 2025 that in 448 people with type 2 diabetes, weight fell by up to 14.5% on subcutaneous dosing (baseline 99.2 kg) versus 2.6% on placebo at week 36; these are best-dose figures from a company release.
  • A ClinicalTrials.gov search on 10 October 2026 returned 31 records, 15 of them phase 3, none with results posted.
  • openFDA Drugs@FDA returned no records and DailyMed no labels for zenagamtide or amycretin on 10 October 2026.

What is amycretin, and is it approved?

Amycretin, now named zenagamtide, is an investigational Novo Nordisk peptide that activates GLP-1 and amylin receptors. openFDA Drugs@FDA returned no record and DailyMed no label for either name on 10 October 2026. The EMA was not searched.

Zenagamtide appears in WHO Proposed INN List 133 (WHO Drug Information, Vol. 39, No. 2, 2025) with the descriptor "glucagon-like peptide 1 (GLP-1) and amylin receptors agonist", molecular formula C343H550N94O116 and CAS 3005889-81-3. The chemical name describes a human GLP-1(7-37) variant (residues 1 to 31) fused through a G4 peptide linker to an artificial 33-peptide amylin receptor agonist (residues 36 to 68), 68-amide, with a fatty diacid side chain on lysine 31. PubChem name lookups on 10 October 2026 for zenagamtide, amycretin and the CAS number returned no record, so no PubChem CID or molecular weight is given.

The WHO list prints neither the name amycretin nor any development code, so the link rests on the peer-reviewed record and the company. Both 2026 Lancet phase 2 papers open with "Zenagamtide (formerly amycretin)", and Novo Nordisk's investor presentation for the first three months of 2026 has a slide titled "Zenagamtide (amycretin) to advance to phase 3 in T2D".

Codes differ by program. The same presentation lists "NN9487 - Oral zenagamtide" and "NN9490 - Sc. zenagamtide" as separate pipeline entries. ClinicalTrials.gov matches: the oral first-in-human trial is NN9487-4830 (NCT05369390) and oral AMAZE 9 is NN9487-8023 (NCT07720271), while the subcutaneous phase 1b/2a is NN9490-7613 (NCT06064006) and AMAZE 1 is NN9490-8021 (NCT07339423). The combined oral and subcutaneous phase 2 diabetes trial (NCT06542874) is filed under NN9490-7678, and registry records use the intervention name NNC0487-0111. NN9487 names the oral program only, so this page does not use it for the molecule as a whole.

On 10 October 2026, openFDA Drugs@FDA returned no records for zenagamtide or amycretin (a pramlintide control returned NDA 021332), and DailyMed drug-name searches for both returned no labels. The EMA was not searched, so status outside the United States is not covered here. Phase 3 trials are registered but have no results.

WHO Proposed INN List 133: GLP-1 and amylin receptors agonist

Regulatory record

World Health Organization. Proposed International Nonproprietary Names: List 133. WHO Drug Information, Vol. 39, No. 2, 2025.

Zenagamtide appears with the descriptor "glucagon-like peptide 1 (GLP-1) and amylin receptors agonist", molecular formula C343H550N94O116 and CAS 3005889-81-3. The chemical name describes a human GLP-1(7-37) variant (residues 1 to 31) fused through a G4 peptide linker to an artificial 33-peptide amylin receptor agonist (residues 36 to 68), 68-amide, with a fatty diacid side chain on lysine 31. The list prints neither the name amycretin nor any development code.

Participants / model
Chemical and regulatory description, not a clinical population
Treatment
Defined acylated peptide
Follow-up
Not applicable
Study design
WHO proposed INN list
Funding
not stated in the source

The list prints no former name or code, so the link between zenagamtide and amycretin rests on the Lancet papers and the company presentation. PubChem name lookups on 10 October 2026 returned no record, so no PubChem CID or molecular weight is given.

Read the original source
Subcutaneous phase 2 in type 2 diabetes: 262 adults, 36 weeks, HbA1c change -0.9% to -1.7%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):621-635. PMID 42532080.

From a mean baseline HbA1c of 7.8%, the estimated HbA1c change ranged from -0.9% at 0.4 mg (difference versus placebo -0.77%, 95% CI -1.26 to -0.28) to -1.7% at 40 mg (-1.56%, 95% CI -2.05 to -1.07), on the efficacy estimand (on-treatment data without rescue medication). Most adverse events were gastrointestinal and mild to moderate. Serious adverse events occurred in 21 (8%) of 261 exposed, three of them on placebo, with no deaths. The paper opens with "Zenagamtide (formerly amycretin)" and describes it as a unimolecular agonist of GLP-1, amylin and calcitonin receptors.

Participants / model
262 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor (HbA1c 7.0 to 10.0%, BMI 23.0 to under 50.0), at 83 sites in 11 countries
Treatment
Subcutaneous zenagamtide once weekly at six doses (0.4, 1.5, 5, 10, 20 or 40 mg; 225 participants) or placebo (37)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial (NCT06542874); efficacy estimand
Funding
Novo Nordisk funded

The abstract gives no weight results; those appear only in a company release. The authors describe calcitonin receptor activity, which the WHO descriptor does not name.

Read the original source
Oral phase 2 in type 2 diabetes: 186 adults, 36 weeks, HbA1c change -0.9% to -1.4%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):607-620. PMID 42532079.

Estimated HbA1c change was -0.9% at 6 mg (difference versus placebo -0.5%, 95% CI -1.04 to -0.04), -1.3% at 25 mg (-0.99%, -1.49 to -0.49) and -1.4% at 50 mg (-1.09%, -1.59 to -0.59). Gastrointestinal adverse events occurred in 14 (26%) of 54, 21 (41%) of 51 and 24 (47%) of 51, versus 7 (23%) of 30 on placebo. Serious adverse events occurred in 7 (4%) of 186 participants, none on placebo, with no deaths.

Participants / model
186 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor
Treatment
Oral tablets once daily: 6 mg (54), 25 mg (51), 50 mg (51) or placebo (30)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial, same 36-week design and sites as the subcutaneous trial (NCT06542874)
Funding
not stated in the source

The abstract gives no weight results. The Lancet papers describe amycretin as zenagamtide, formerly amycretin.

Read the original source
Novo Nordisk Q1 2026 presentation: oral NN9487 and subcutaneous NN9490 as separate programs

Regulatory record

Novo Nordisk A/S. Investor presentation for the first three months of 2026.

A slide is titled "Zenagamtide (amycretin) to advance to phase 3 in T2D", and a pipeline slide lists "NN9487 - Oral zenagamtide" and "NN9490 - Sc. zenagamtide" as separate entries. ClinicalTrials.gov matches: the oral first-in-human trial is NN9487-4830 (NCT05369390) and oral AMAZE 9 is NN9487-8023 (NCT07720271), while the subcutaneous phase 1b/2a is NN9490-7613 (NCT06064006) and AMAZE 1 is NN9490-8021 (NCT07339423). The combined oral and subcutaneous phase 2 diabetes trial (NCT06542874) is filed under NN9490-7678, and registry records use the intervention name NNC0487-0111.

Participants / model
Not a clinical population
Treatment
Not applicable
Follow-up
Q1 2026 presentation
Study design
Company statement plus trial registry matches
Funding
not stated in the source

NN9487 names the oral program only, so it is not used for the molecule as a whole. The slide gives HbA1c falls of up to 1.8 points subcutaneous and 1.5 oral.

Read the original source
FDA record searches, 10 October 2026: no record or label; JAMA news item on unapproved sale

Regulatory record

Rubin R. JAMA. 2026. PMID 42853576.

openFDA Drugs@FDA returned no records for zenagamtide or amycretin (a pramlintide control returned NDA 021332), and DailyMed drug-name searches for both returned no labels. A JAMA Medical News article dated 9 October 2026 describes a black market for two unapproved GLP-1 drugs, retatrutide and zenagamtide. The EMA was not searched.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated regulator database search and news item
Funding
not stated in the source

Only the plain-language summary of the JAMA item was read. A search result shows what the databases returned on that date, and it is US-scoped.

Read the original source

What did the phase 1 and phase 2 studies find?

In a phase 1b/2a trial in 125 adults with overweight or obesity, estimated mean weight change at 60 mg was -24.3% versus -1.1% on placebo at week 36, with a large number of withdrawals and no count given. In two randomized phase 2 trials in type 2 diabetes, estimated HbA1c change reached -1.7% (40 mg subcutaneous) and -1.4% (50 mg oral) at week 36.

In a phase 1b/2a trial at one US site, 125 adults aged 18 to 55 with overweight or obesity (BMI 27.0 to 39.9) were randomized to once-weekly subcutaneous amycretin (101) or placebo (24). Estimated mean weight change was -24.3% on amycretin versus -1.1% on placebo at 60 mg (week 36), -22.0% versus 1.9% at 20 mg (week 36), -16.2% versus 2.3% at 5 mg (week 28) and -9.7% versus 2.0% at 1.25 mg (week 20). These are each group's estimated mean change, not placebo-adjusted differences. The arms ran for different lengths and were not compared with each other. The abstract says a large number of participants withdrew, many for reasons unrelated to adverse events, and gives no count, so the dropout behind these means is not known here. Ten of the 12 authors list Novo Nordisk affiliations. The trial is registered as NCT06064006.

The first-in-human oral phase 1 trial, also at one US site, enrolled 144 adults aged 18 to 55 with overweight or obesity (48 in a single-dose part, 36 in a 10-day part, 60 in a 12-week part). Single oral doses ran from 1 to 25 mg, and the 12-week part escalated once-daily doses up to 50 mg or 2 x 50 mg. Plasma levels were consistent with dose proportionality. The abstract gives no weight figures. The trial is registered as NCT05369390.

The subcutaneous phase 2 trial in type 2 diabetes randomized 262 adults at 83 sites in 11 countries for 36 weeks: 225 to zenagamtide at six doses (0.4, 1.5, 5, 10, 20 or 40 mg once weekly) and 37 to placebo. All were on metformin with or without an SGLT2 inhibitor, with a mean baseline HbA1c of 7.8%. On the efficacy estimand (on-treatment data without rescue medication), the estimated HbA1c change ranged from -0.9% at 0.4 mg (difference versus placebo -0.77%, 95% CI -1.26 to -0.28) to -1.7% at 40 mg (-1.56%, 95% CI -2.05 to -1.07). The trial is registered as NCT06542874.

The oral phase 2 trial used the same 36-week design and sites. It randomized 186 adults to once-daily 6 mg (54), 25 mg (51), 50 mg (51) or placebo (30). Estimated HbA1c change was -0.9% at 6 mg (difference versus placebo -0.5%, 95% CI -1.04 to -0.04), -1.3% at 25 mg (-0.99%, -1.49 to -0.49) and -1.4% at 50 mg (-1.09%, -1.59 to -0.59).

Subcutaneous phase 1b/2a: 125 adults, weight change -24.3% at 60 mg versus -1.1% on placebo, heavy dropout

Randomized controlled trial

Dahl K et al. Lancet. 2025;406(10499):149-162. PMID 40550231.

Estimated mean weight change versus placebo was -24.3% versus -1.1% at 60 mg (week 36), -22.0% versus 1.9% at 20 mg (week 36), -16.2% versus 2.3% at 5 mg (week 28) and -9.7% versus 2.0% at 1.25 mg (week 20). The arms ran for different lengths and were not compared with each other. Gastrointestinal events were most common and mostly mild to moderate. The abstract says a large number of participants withdrew, many for reasons unrelated to adverse events, and gives no count.

Participants / model
125 adults aged 18 to 55 with overweight or obesity (BMI 27.0 to 39.9) at one US site; 101 on amycretin and 24 on placebo
Treatment
Subcutaneous amycretin once weekly, or placebo
Follow-up
20 to 36 weeks depending on the dose arm
Study design
Randomized phase 1b/2a trial (NCT06064006)
Funding
not stated in the source

Single-site, small, and sponsor-affiliated: 10 of the 12 authors list Novo Nordisk affiliations. The dropout count is not in the abstract.

Read the original source
Oral phase 1: 144 adults, single and multiple ascending doses, no weight figures in the abstract

Randomized controlled trial

Gasiorek A et al. Lancet. 2025;406(10499):135-148. PMID 40550229.

There were 364 treatment-emergent adverse events in 89 (62%) of 144 participants, all mild or moderate and dose-dependent, and 180 (49%) of the 364 were gastrointestinal. There were no deaths. Plasma levels were consistent with dose proportionality. The abstract gives no weight figures.

Participants / model
144 adults aged 18 to 55 with overweight or obesity at one US site (BMI 25.0 to 34.9 in the single-dose and 10-day parts, 27.0 to 39.9 in the 12-week part)
Treatment
Oral tablets: single doses of 1 to 25 mg (48 participants), a 10-day part (36) and a 12-week part (60) escalating once-daily doses up to 50 mg or 2 x 50 mg
Follow-up
Single dose, 10 days and 12 weeks in three parts
Study design
Randomized phase 1 first-in-human trial, single and multiple ascending doses (NCT05369390)
Funding
not stated in the source

Exploratory weight and fasting glucose were secondary measures; the abstract reports neither.

Read the original source
Subcutaneous phase 2 in type 2 diabetes: 262 adults, 36 weeks, HbA1c change -0.9% to -1.7%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):621-635. PMID 42532080.

From a mean baseline HbA1c of 7.8%, the estimated HbA1c change ranged from -0.9% at 0.4 mg (difference versus placebo -0.77%, 95% CI -1.26 to -0.28) to -1.7% at 40 mg (-1.56%, 95% CI -2.05 to -1.07), on the efficacy estimand (on-treatment data without rescue medication). Most adverse events were gastrointestinal and mild to moderate. Serious adverse events occurred in 21 (8%) of 261 exposed, three of them on placebo, with no deaths. The paper opens with "Zenagamtide (formerly amycretin)" and describes it as a unimolecular agonist of GLP-1, amylin and calcitonin receptors.

Participants / model
262 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor (HbA1c 7.0 to 10.0%, BMI 23.0 to under 50.0), at 83 sites in 11 countries
Treatment
Subcutaneous zenagamtide once weekly at six doses (0.4, 1.5, 5, 10, 20 or 40 mg; 225 participants) or placebo (37)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial (NCT06542874); efficacy estimand
Funding
Novo Nordisk funded

The abstract gives no weight results; those appear only in a company release. The authors describe calcitonin receptor activity, which the WHO descriptor does not name.

Read the original source
Oral phase 2 in type 2 diabetes: 186 adults, 36 weeks, HbA1c change -0.9% to -1.4%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):607-620. PMID 42532079.

Estimated HbA1c change was -0.9% at 6 mg (difference versus placebo -0.5%, 95% CI -1.04 to -0.04), -1.3% at 25 mg (-0.99%, -1.49 to -0.49) and -1.4% at 50 mg (-1.09%, -1.59 to -0.59). Gastrointestinal adverse events occurred in 14 (26%) of 54, 21 (41%) of 51 and 24 (47%) of 51, versus 7 (23%) of 30 on placebo. Serious adverse events occurred in 7 (4%) of 186 participants, none on placebo, with no deaths.

Participants / model
186 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor
Treatment
Oral tablets once daily: 6 mg (54), 25 mg (51), 50 mg (51) or placebo (30)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial, same 36-week design and sites as the subcutaneous trial (NCT06542874)
Funding
not stated in the source

The abstract gives no weight results. The Lancet papers describe amycretin as zenagamtide, formerly amycretin.

Read the original source

What weight results has the company reported in type 2 diabetes?

On 25 November 2025 the company reported that in 448 people with type 2 diabetes, weight fell by up to 14.5% on subcutaneous dosing versus 2.6% on placebo, and by up to 10.1% on oral dosing versus 2.5% on placebo, at week 36. These are best-dose figures from a company release, not peer reviewed.

Neither Lancet abstract gives weight results. Weight figures from the phase 2 diabetes trial appear in a company release and an investor slide. In Company Announcement No 38 / 2025, dated 25 November 2025 and using the name amycretin, the company reported that in 448 people with type 2 diabetes, weight fell by up to 14.5% on subcutaneous dosing (baseline 99.2 kg) versus 2.6% on placebo, and by up to 10.1% on oral dosing (baseline 101.1 kg) versus 2.5% on placebo, at week 36.

These are best-dose up-to figures, and the release notes that the top subcutaneous dose had only 4 weeks at maintenance. The release and the Q1 2026 slide give HbA1c falls of up to 1.8 points subcutaneous and 1.5 oral; the Lancet efficacy-estimand figure for the top subcutaneous dose is -1.7%.

Company statement, 25 November 2025: weight down by up to 14.5% subcutaneous and 10.1% oral at week 36

Clinical trial

Novo Nordisk A/S. Company Announcement No 38 / 2025, dated 25 November 2025, which uses the name amycretin.

The company reported that in 448 people with type 2 diabetes, weight fell by up to 14.5% on subcutaneous dosing (baseline 99.2 kg) versus 2.6% on placebo, and by up to 10.1% on oral dosing (baseline 101.1 kg) versus 2.5% on placebo, at week 36. The release notes that the top subcutaneous dose had only 4 weeks at maintenance. The release and the Q1 2026 slide give HbA1c falls of up to 1.8 points subcutaneous and 1.5 oral.

Participants / model
448 adults with type 2 diabetes
Treatment
Subcutaneous once weekly and oral once daily
Follow-up
Week 36
Study design
Company announcement of a randomized phase 2 trial; not peer reviewed
Funding
not stated in the source

These are best-dose up-to figures from the company. The Lancet efficacy-estimand HbA1c figure for the top subcutaneous dose is -1.7%, against the company's up-to 1.8 points.

Read the original source
Novo Nordisk Q1 2026 presentation: oral NN9487 and subcutaneous NN9490 as separate programs

Regulatory record

Novo Nordisk A/S. Investor presentation for the first three months of 2026.

A slide is titled "Zenagamtide (amycretin) to advance to phase 3 in T2D", and a pipeline slide lists "NN9487 - Oral zenagamtide" and "NN9490 - Sc. zenagamtide" as separate entries. ClinicalTrials.gov matches: the oral first-in-human trial is NN9487-4830 (NCT05369390) and oral AMAZE 9 is NN9487-8023 (NCT07720271), while the subcutaneous phase 1b/2a is NN9490-7613 (NCT06064006) and AMAZE 1 is NN9490-8021 (NCT07339423). The combined oral and subcutaneous phase 2 diabetes trial (NCT06542874) is filed under NN9490-7678, and registry records use the intervention name NNC0487-0111.

Participants / model
Not a clinical population
Treatment
Not applicable
Follow-up
Q1 2026 presentation
Study design
Company statement plus trial registry matches
Funding
not stated in the source

NN9487 names the oral program only, so it is not used for the molecule as a whole. The slide gives HbA1c falls of up to 1.8 points subcutaneous and 1.5 oral.

Read the original source
Subcutaneous phase 2 in type 2 diabetes: 262 adults, 36 weeks, HbA1c change -0.9% to -1.7%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):621-635. PMID 42532080.

From a mean baseline HbA1c of 7.8%, the estimated HbA1c change ranged from -0.9% at 0.4 mg (difference versus placebo -0.77%, 95% CI -1.26 to -0.28) to -1.7% at 40 mg (-1.56%, 95% CI -2.05 to -1.07), on the efficacy estimand (on-treatment data without rescue medication). Most adverse events were gastrointestinal and mild to moderate. Serious adverse events occurred in 21 (8%) of 261 exposed, three of them on placebo, with no deaths. The paper opens with "Zenagamtide (formerly amycretin)" and describes it as a unimolecular agonist of GLP-1, amylin and calcitonin receptors.

Participants / model
262 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor (HbA1c 7.0 to 10.0%, BMI 23.0 to under 50.0), at 83 sites in 11 countries
Treatment
Subcutaneous zenagamtide once weekly at six doses (0.4, 1.5, 5, 10, 20 or 40 mg; 225 participants) or placebo (37)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial (NCT06542874); efficacy estimand
Funding
Novo Nordisk funded

The abstract gives no weight results; those appear only in a company release. The authors describe calcitonin receptor activity, which the WHO descriptor does not name.

Read the original source

Has phase 3 started, and what is registered?

Phase 3 has started. A ClinicalTrials.gov search on 10 October 2026 for zenagamtide, amycretin or NNC0487-0111 returned 31 records, 15 of them phase 3, none with results posted. A registration is not an outcome.

A ClinicalTrials.gov search on 10 October 2026 for zenagamtide, amycretin or NNC0487-0111 returned 31 records, 15 of them phase 3, none with results posted. Examples: AMAZE 1 (NCT07339423) compares subcutaneous zenagamtide with placebo, with 1,150 estimated participants, a start on 24 February 2026 and weight change to week 84 as the outcome. AMAZE 9 (NCT07720271) compares oral zenagamtide with placebo, with 950 estimated, a start on 31 August 2026 and weight change to week 76. AMAZE 7 (NCT07668414) compares against semaglutide, with 650 estimated and a start on 22 September 2026. AMBITION 7 (NCT07797335) compares against insulin glargine in type 2 diabetes, with 1,778 estimated, a start on 24 August 2026 and an HbA1c non-inferiority outcome at week 52. AMBIENCE (NCT07861100) has 8,500 estimated participants, is not yet recruiting, has a listed start of 26 October 2026 and a four-point MACE outcome.

These are registrations, planned populations and estimated sizes. A registration is not an outcome, and no phase 3 result exists.

Registry, 10 October 2026: 31 records, 15 phase 3, none with results

Trial registry record

ClinicalTrials.gov search run on 10 October 2026 for zenagamtide, amycretin or NNC0487-0111, with AMAZE 1 (NCT07339423) as the reference record.

The search returned 31 records, 15 of them phase 3, none with results posted. Examples: AMAZE 1 (NCT07339423, subcutaneous versus placebo, 1,150 estimated, started 24 February 2026, weight change to week 84); AMAZE 9 (NCT07720271, oral versus placebo, 950 estimated, started 31 August 2026, weight change to week 76); AMAZE 7 (NCT07668414, versus semaglutide, 650 estimated, started 22 September 2026); AMBITION 7 (NCT07797335, type 2 diabetes versus insulin glargine, 1,778 estimated, started 24 August 2026, HbA1c non-inferiority at week 52); and AMBIENCE (NCT07861100, 8,500 estimated, not yet recruiting, listed start 26 October 2026, four-point MACE). A registration is not an outcome.

Participants / model
Adults with obesity, type 2 diabetes or cardiovascular disease (planned populations)
Treatment
Subcutaneous once weekly or oral once daily
Follow-up
Primary outcomes planned at weeks 52 to 84
Study design
Official trial registry
Funding
not stated in the source

Registrations and estimated sizes, not outcomes. No phase 3 results exist.

Read the original source
Novo Nordisk Q1 2026 presentation: oral NN9487 and subcutaneous NN9490 as separate programs

Regulatory record

Novo Nordisk A/S. Investor presentation for the first three months of 2026.

A slide is titled "Zenagamtide (amycretin) to advance to phase 3 in T2D", and a pipeline slide lists "NN9487 - Oral zenagamtide" and "NN9490 - Sc. zenagamtide" as separate entries. ClinicalTrials.gov matches: the oral first-in-human trial is NN9487-4830 (NCT05369390) and oral AMAZE 9 is NN9487-8023 (NCT07720271), while the subcutaneous phase 1b/2a is NN9490-7613 (NCT06064006) and AMAZE 1 is NN9490-8021 (NCT07339423). The combined oral and subcutaneous phase 2 diabetes trial (NCT06542874) is filed under NN9490-7678, and registry records use the intervention name NNC0487-0111.

Participants / model
Not a clinical population
Treatment
Not applicable
Follow-up
Q1 2026 presentation
Study design
Company statement plus trial registry matches
Funding
not stated in the source

NN9487 names the oral program only, so it is not used for the molecule as a whole. The slide gives HbA1c falls of up to 1.8 points subcutaneous and 1.5 oral.

Read the original source

Is the supplier description of amycretin accurate?

Largely, for the investigational drug, with one correction. Novo Nordisk's drug is a GLP-1 and amylin receptor co-agonist studied orally and by subcutaneous injection, with phase 2 type 2 diabetes data, but NN9487 is the code of the oral program only. Nothing supports an approved or standardized product, so anything sold online is unapproved and cannot be matched to the studied drug.

Sellers describe amycretin (now zenagamtide, code NN9487) as a Novo Nordisk unimolecular GLP-1 and amylin receptor co-agonist given orally and by subcutaneous injection, with phase 2 type 2 diabetes data. That description is accurate for the investigational drug: the Lancet phase 2 papers cover both routes. The one correction is the code. NN9487 is the oral program only, and the subcutaneous program is NN9490.

Nothing in the sources reviewed supports an approved or standardized product. openFDA Drugs@FDA and DailyMed returned no records or labels for either name on 10 October 2026. A JAMA Medical News article dated 9 October 2026 (only its plain-language summary was read here) describes a black market for two unapproved GLP-1 drugs, retatrutide and zenagamtide. Anything sold online is therefore unapproved and cannot be matched to the studied drug.

Novo Nordisk Q1 2026 presentation: oral NN9487 and subcutaneous NN9490 as separate programs

Regulatory record

Novo Nordisk A/S. Investor presentation for the first three months of 2026.

A slide is titled "Zenagamtide (amycretin) to advance to phase 3 in T2D", and a pipeline slide lists "NN9487 - Oral zenagamtide" and "NN9490 - Sc. zenagamtide" as separate entries. ClinicalTrials.gov matches: the oral first-in-human trial is NN9487-4830 (NCT05369390) and oral AMAZE 9 is NN9487-8023 (NCT07720271), while the subcutaneous phase 1b/2a is NN9490-7613 (NCT06064006) and AMAZE 1 is NN9490-8021 (NCT07339423). The combined oral and subcutaneous phase 2 diabetes trial (NCT06542874) is filed under NN9490-7678, and registry records use the intervention name NNC0487-0111.

Participants / model
Not a clinical population
Treatment
Not applicable
Follow-up
Q1 2026 presentation
Study design
Company statement plus trial registry matches
Funding
not stated in the source

NN9487 names the oral program only, so it is not used for the molecule as a whole. The slide gives HbA1c falls of up to 1.8 points subcutaneous and 1.5 oral.

Read the original source
FDA record searches, 10 October 2026: no record or label; JAMA news item on unapproved sale

Regulatory record

Rubin R. JAMA. 2026. PMID 42853576.

openFDA Drugs@FDA returned no records for zenagamtide or amycretin (a pramlintide control returned NDA 021332), and DailyMed drug-name searches for both returned no labels. A JAMA Medical News article dated 9 October 2026 describes a black market for two unapproved GLP-1 drugs, retatrutide and zenagamtide. The EMA was not searched.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated regulator database search and news item
Funding
not stated in the source

Only the plain-language summary of the JAMA item was read. A search result shows what the databases returned on that date, and it is US-scoped.

Read the original source
Subcutaneous phase 2 in type 2 diabetes: 262 adults, 36 weeks, HbA1c change -0.9% to -1.7%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):621-635. PMID 42532080.

From a mean baseline HbA1c of 7.8%, the estimated HbA1c change ranged from -0.9% at 0.4 mg (difference versus placebo -0.77%, 95% CI -1.26 to -0.28) to -1.7% at 40 mg (-1.56%, 95% CI -2.05 to -1.07), on the efficacy estimand (on-treatment data without rescue medication). Most adverse events were gastrointestinal and mild to moderate. Serious adverse events occurred in 21 (8%) of 261 exposed, three of them on placebo, with no deaths. The paper opens with "Zenagamtide (formerly amycretin)" and describes it as a unimolecular agonist of GLP-1, amylin and calcitonin receptors.

Participants / model
262 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor (HbA1c 7.0 to 10.0%, BMI 23.0 to under 50.0), at 83 sites in 11 countries
Treatment
Subcutaneous zenagamtide once weekly at six doses (0.4, 1.5, 5, 10, 20 or 40 mg; 225 participants) or placebo (37)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial (NCT06542874); efficacy estimand
Funding
Novo Nordisk funded

The abstract gives no weight results; those appear only in a company release. The authors describe calcitonin receptor activity, which the WHO descriptor does not name.

Read the original source
Oral phase 2 in type 2 diabetes: 186 adults, 36 weeks, HbA1c change -0.9% to -1.4%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):607-620. PMID 42532079.

Estimated HbA1c change was -0.9% at 6 mg (difference versus placebo -0.5%, 95% CI -1.04 to -0.04), -1.3% at 25 mg (-0.99%, -1.49 to -0.49) and -1.4% at 50 mg (-1.09%, -1.59 to -0.59). Gastrointestinal adverse events occurred in 14 (26%) of 54, 21 (41%) of 51 and 24 (47%) of 51, versus 7 (23%) of 30 on placebo. Serious adverse events occurred in 7 (4%) of 186 participants, none on placebo, with no deaths.

Participants / model
186 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor
Treatment
Oral tablets once daily: 6 mg (54), 25 mg (51), 50 mg (51) or placebo (30)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial, same 36-week design and sites as the subcutaneous trial (NCT06542874)
Funding
not stated in the source

The abstract gives no weight results. The Lancet papers describe amycretin as zenagamtide, formerly amycretin.

Read the original source

How does amycretin work, and how is it handled in kidney impairment?

Amycretin is a single peptide built to activate GLP-1 and amylin receptors, and its authors also describe calcitonin receptor activity. After one subcutaneous dose, exposure in adults with kidney impairment, including end-stage renal disease, was similar to normal function in a 42-adult study. No half-life is given in the sources reviewed.

WHO describes zenagamtide as an agonist of GLP-1 and amylin receptors. The chemical name describes a GLP-1 variant joined by a linker to an artificial amylin receptor agonist, with a fatty diacid side chain on lysine 31. Both 2026 Lancet phase 2 papers describe it as a unimolecular agonist of GLP-1, amylin and calcitonin receptors. The WHO descriptor names only the GLP-1 and amylin receptors, so the calcitonin receptor activity comes from the authors, not from the WHO entry.

In diet-induced obese rats, 21 days of amycretin cut total energy intake by 47% and body weight by 18% (95% CI of mean change from pre-treatment: vehicle 6.56 to 8.47% versus amycretin -10.48 to -12.74%) while maintaining energy expenditure. Insulin sensitivity improved on a hyperinsulinaemic euglycaemic clamp and liver steatosis fell. In cell-based systems it activated human, mouse and rat GLP-1, amylin and calcitonin receptors. All authors are Novo Nordisk staff, the abstract does not state the route, and rodent data do not transfer to people.

In a clinical pharmacology study, 42 adults with BMI 20.0 to 39.9 (14 with normal renal function and 7 in each of four impairment groups, including end-stage renal disease) received a single 0.3 mg subcutaneous dose. Geometric mean AUC0-inf was 520 to 715 h x nmol/L across impairment groups versus 543 h x nmol/L with normal function, and Cmax was 2.8 to 3.5 versus 3.2 nmol/L. The study is registered as NCT06559527. No half-life or Tmax appears in the sources reviewed.

WHO Proposed INN List 133: GLP-1 and amylin receptors agonist

Regulatory record

World Health Organization. Proposed International Nonproprietary Names: List 133. WHO Drug Information, Vol. 39, No. 2, 2025.

Zenagamtide appears with the descriptor "glucagon-like peptide 1 (GLP-1) and amylin receptors agonist", molecular formula C343H550N94O116 and CAS 3005889-81-3. The chemical name describes a human GLP-1(7-37) variant (residues 1 to 31) fused through a G4 peptide linker to an artificial 33-peptide amylin receptor agonist (residues 36 to 68), 68-amide, with a fatty diacid side chain on lysine 31. The list prints neither the name amycretin nor any development code.

Participants / model
Chemical and regulatory description, not a clinical population
Treatment
Defined acylated peptide
Follow-up
Not applicable
Study design
WHO proposed INN list
Funding
not stated in the source

The list prints no former name or code, so the link between zenagamtide and amycretin rests on the Lancet papers and the company presentation. PubChem name lookups on 10 October 2026 returned no record, so no PubChem CID or molecular weight is given.

Read the original source
Subcutaneous phase 2 in type 2 diabetes: 262 adults, 36 weeks, HbA1c change -0.9% to -1.7%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):621-635. PMID 42532080.

From a mean baseline HbA1c of 7.8%, the estimated HbA1c change ranged from -0.9% at 0.4 mg (difference versus placebo -0.77%, 95% CI -1.26 to -0.28) to -1.7% at 40 mg (-1.56%, 95% CI -2.05 to -1.07), on the efficacy estimand (on-treatment data without rescue medication). Most adverse events were gastrointestinal and mild to moderate. Serious adverse events occurred in 21 (8%) of 261 exposed, three of them on placebo, with no deaths. The paper opens with "Zenagamtide (formerly amycretin)" and describes it as a unimolecular agonist of GLP-1, amylin and calcitonin receptors.

Participants / model
262 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor (HbA1c 7.0 to 10.0%, BMI 23.0 to under 50.0), at 83 sites in 11 countries
Treatment
Subcutaneous zenagamtide once weekly at six doses (0.4, 1.5, 5, 10, 20 or 40 mg; 225 participants) or placebo (37)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial (NCT06542874); efficacy estimand
Funding
Novo Nordisk funded

The abstract gives no weight results; those appear only in a company release. The authors describe calcitonin receptor activity, which the WHO descriptor does not name.

Read the original source
Oral phase 2 in type 2 diabetes: 186 adults, 36 weeks, HbA1c change -0.9% to -1.4%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):607-620. PMID 42532079.

Estimated HbA1c change was -0.9% at 6 mg (difference versus placebo -0.5%, 95% CI -1.04 to -0.04), -1.3% at 25 mg (-0.99%, -1.49 to -0.49) and -1.4% at 50 mg (-1.09%, -1.59 to -0.59). Gastrointestinal adverse events occurred in 14 (26%) of 54, 21 (41%) of 51 and 24 (47%) of 51, versus 7 (23%) of 30 on placebo. Serious adverse events occurred in 7 (4%) of 186 participants, none on placebo, with no deaths.

Participants / model
186 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor
Treatment
Oral tablets once daily: 6 mg (54), 25 mg (51), 50 mg (51) or placebo (30)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial, same 36-week design and sites as the subcutaneous trial (NCT06542874)
Funding
not stated in the source

The abstract gives no weight results. The Lancet papers describe amycretin as zenagamtide, formerly amycretin.

Read the original source
Rats: 21 days, energy intake down 47%, body weight down 18%; receptor activation in cells

Animal study

Kuhre RE et al. EBioMedicine. 2025;118:105862. PMID 40706446.

In diet-induced obese rats, 21 days of amycretin cut total energy intake by 47% and body weight by 18% (95% CI of mean change from pre-treatment: vehicle 6.56 to 8.47% versus amycretin -10.48 to -12.74%) while maintaining energy expenditure. Insulin sensitivity improved on a hyperinsulinaemic euglycaemic clamp and liver steatosis fell. In cell-based systems it activated human, mouse and rat GLP-1, amylin and calcitonin receptors.

Participants / model
Diet-induced obese rats and mice; cell-based receptor assays
Treatment
Amycretin; route not stated in the abstract
Follow-up
21 days
Study design
Original preclinical study
Funding
not stated in the source

All authors are Novo Nordisk staff. The abstract states no route or dose. Rodent data do not transfer to people.

Read the original source
Renal impairment study: 42 adults, exposure similar across groups

Clinical trial

Oldenburg LIK et al. Diabetes Obes Metab. 2026;28(10):8946-8954. PMID 42443140.

Geometric mean AUC0-inf was 520 to 715 h x nmol/L across impairment groups versus 543 h x nmol/L with normal function, and Cmax was 2.8 to 3.5 versus 3.2 nmol/L. Treatment-emergent adverse events occurred in 30 (71.4%) of the 42 participants, none serious or severe.

Participants / model
42 adults with BMI 20.0 to 39.9: 14 with normal renal function and 7 in each of four impairment groups, including end-stage renal disease
Treatment
Single 0.3 mg subcutaneous dose
Follow-up
Single dose
Study design
Clinical pharmacology study (NCT06559527)
Funding
not stated in the source

Novo Nordisk authors. The abstract gives no half-life or Tmax.

Read the original source

What adverse events did the studies report?

Gastrointestinal adverse events were the most common in every trial and mostly mild to moderate. In the phase 2 diabetes trials, serious adverse events occurred in 21 (8%) of 261 exposed on subcutaneous dosing (three on placebo) and 7 (4%) of 186 on oral dosing (none on placebo), with no deaths. No phase 3 result or long-term safety data exist.

In the first-in-human oral trial, 364 treatment-emergent adverse events occurred in 89 (62%) of 144 participants, all mild or moderate and dose-dependent, and 180 (49%) of the 364 were gastrointestinal. There were no deaths. In the subcutaneous phase 1b/2a trial, gastrointestinal events were most common and mostly mild to moderate. The abstract says a large number of participants withdrew, many for reasons unrelated to adverse events, and gives no count.

In the subcutaneous phase 2 trial in type 2 diabetes, most adverse events were gastrointestinal and mild to moderate. Serious adverse events occurred in 21 (8%) of 261 exposed participants, three of them on placebo. There were no deaths. In the oral phase 2 trial, gastrointestinal adverse events occurred in 14 (26%) of 54 at 6 mg, 21 (41%) of 51 at 25 mg and 24 (47%) of 51 at 50 mg, versus 7 (23%) of 30 on placebo. Serious adverse events occurred in 7 (4%) of 186 participants, none on placebo, with no deaths.

In the single-dose kidney impairment study, treatment-emergent adverse events occurred in 30 (71.4%) of 42 participants, none serious or severe.

No phase 3 result, long-term safety dataset or approval exists. Anything sold online cannot be matched to the studied drug, so these findings do not describe it.

Oral phase 1: 144 adults, single and multiple ascending doses, no weight figures in the abstract

Randomized controlled trial

Gasiorek A et al. Lancet. 2025;406(10499):135-148. PMID 40550229.

There were 364 treatment-emergent adverse events in 89 (62%) of 144 participants, all mild or moderate and dose-dependent, and 180 (49%) of the 364 were gastrointestinal. There were no deaths. Plasma levels were consistent with dose proportionality. The abstract gives no weight figures.

Participants / model
144 adults aged 18 to 55 with overweight or obesity at one US site (BMI 25.0 to 34.9 in the single-dose and 10-day parts, 27.0 to 39.9 in the 12-week part)
Treatment
Oral tablets: single doses of 1 to 25 mg (48 participants), a 10-day part (36) and a 12-week part (60) escalating once-daily doses up to 50 mg or 2 x 50 mg
Follow-up
Single dose, 10 days and 12 weeks in three parts
Study design
Randomized phase 1 first-in-human trial, single and multiple ascending doses (NCT05369390)
Funding
not stated in the source

Exploratory weight and fasting glucose were secondary measures; the abstract reports neither.

Read the original source
Subcutaneous phase 1b/2a: 125 adults, weight change -24.3% at 60 mg versus -1.1% on placebo, heavy dropout

Randomized controlled trial

Dahl K et al. Lancet. 2025;406(10499):149-162. PMID 40550231.

Estimated mean weight change versus placebo was -24.3% versus -1.1% at 60 mg (week 36), -22.0% versus 1.9% at 20 mg (week 36), -16.2% versus 2.3% at 5 mg (week 28) and -9.7% versus 2.0% at 1.25 mg (week 20). The arms ran for different lengths and were not compared with each other. Gastrointestinal events were most common and mostly mild to moderate. The abstract says a large number of participants withdrew, many for reasons unrelated to adverse events, and gives no count.

Participants / model
125 adults aged 18 to 55 with overweight or obesity (BMI 27.0 to 39.9) at one US site; 101 on amycretin and 24 on placebo
Treatment
Subcutaneous amycretin once weekly, or placebo
Follow-up
20 to 36 weeks depending on the dose arm
Study design
Randomized phase 1b/2a trial (NCT06064006)
Funding
not stated in the source

Single-site, small, and sponsor-affiliated: 10 of the 12 authors list Novo Nordisk affiliations. The dropout count is not in the abstract.

Read the original source
Subcutaneous phase 2 in type 2 diabetes: 262 adults, 36 weeks, HbA1c change -0.9% to -1.7%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):621-635. PMID 42532080.

From a mean baseline HbA1c of 7.8%, the estimated HbA1c change ranged from -0.9% at 0.4 mg (difference versus placebo -0.77%, 95% CI -1.26 to -0.28) to -1.7% at 40 mg (-1.56%, 95% CI -2.05 to -1.07), on the efficacy estimand (on-treatment data without rescue medication). Most adverse events were gastrointestinal and mild to moderate. Serious adverse events occurred in 21 (8%) of 261 exposed, three of them on placebo, with no deaths. The paper opens with "Zenagamtide (formerly amycretin)" and describes it as a unimolecular agonist of GLP-1, amylin and calcitonin receptors.

Participants / model
262 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor (HbA1c 7.0 to 10.0%, BMI 23.0 to under 50.0), at 83 sites in 11 countries
Treatment
Subcutaneous zenagamtide once weekly at six doses (0.4, 1.5, 5, 10, 20 or 40 mg; 225 participants) or placebo (37)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial (NCT06542874); efficacy estimand
Funding
Novo Nordisk funded

The abstract gives no weight results; those appear only in a company release. The authors describe calcitonin receptor activity, which the WHO descriptor does not name.

Read the original source
Oral phase 2 in type 2 diabetes: 186 adults, 36 weeks, HbA1c change -0.9% to -1.4%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):607-620. PMID 42532079.

Estimated HbA1c change was -0.9% at 6 mg (difference versus placebo -0.5%, 95% CI -1.04 to -0.04), -1.3% at 25 mg (-0.99%, -1.49 to -0.49) and -1.4% at 50 mg (-1.09%, -1.59 to -0.59). Gastrointestinal adverse events occurred in 14 (26%) of 54, 21 (41%) of 51 and 24 (47%) of 51, versus 7 (23%) of 30 on placebo. Serious adverse events occurred in 7 (4%) of 186 participants, none on placebo, with no deaths.

Participants / model
186 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor
Treatment
Oral tablets once daily: 6 mg (54), 25 mg (51), 50 mg (51) or placebo (30)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial, same 36-week design and sites as the subcutaneous trial (NCT06542874)
Funding
not stated in the source

The abstract gives no weight results. The Lancet papers describe amycretin as zenagamtide, formerly amycretin.

Read the original source
Renal impairment study: 42 adults, exposure similar across groups

Clinical trial

Oldenburg LIK et al. Diabetes Obes Metab. 2026;28(10):8946-8954. PMID 42443140.

Geometric mean AUC0-inf was 520 to 715 h x nmol/L across impairment groups versus 543 h x nmol/L with normal function, and Cmax was 2.8 to 3.5 versus 3.2 nmol/L. Treatment-emergent adverse events occurred in 30 (71.4%) of the 42 participants, none serious or severe.

Participants / model
42 adults with BMI 20.0 to 39.9: 14 with normal renal function and 7 in each of four impairment groups, including end-stage renal disease
Treatment
Single 0.3 mg subcutaneous dose
Follow-up
Single dose
Study design
Clinical pharmacology study (NCT06559527)
Funding
not stated in the source

Novo Nordisk authors. The abstract gives no half-life or Tmax.

Read the original source

Why does amycretin sit in B tier?

The GLP-1 and amylin description is consistent across the sources, and the early outcomes are large: two randomized phase 2 diabetes trials in The Lancet and a phase 1b/2a obesity trial with an estimated mean weight change of -24.3% at 60 mg. B stops short of a higher grade because the obesity data come from one small single-site trial with heavy, uncounted dropout, the diabetes weight data are company-reported, and there is no phase 3 result, approval or long-term safety dataset.

The B rests on two randomized phase 2 type 2 diabetes trials with dose-related HbA1c falls and a small phase 1b/2a obesity trial with large estimated weight changes. The obesity figures come from a single-site trial in which a large number of participants withdrew with no count in the abstract, and the weight results in type 2 diabetes are company statements only.

It stops there because phase 3 has started but has no results, no approval record or long-term safety dataset exists, and anything sold online cannot be matched to the studied drug. This is the same footing as other amylin-class pipeline drugs.

Subcutaneous phase 2 in type 2 diabetes: 262 adults, 36 weeks, HbA1c change -0.9% to -1.7%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):621-635. PMID 42532080.

From a mean baseline HbA1c of 7.8%, the estimated HbA1c change ranged from -0.9% at 0.4 mg (difference versus placebo -0.77%, 95% CI -1.26 to -0.28) to -1.7% at 40 mg (-1.56%, 95% CI -2.05 to -1.07), on the efficacy estimand (on-treatment data without rescue medication). Most adverse events were gastrointestinal and mild to moderate. Serious adverse events occurred in 21 (8%) of 261 exposed, three of them on placebo, with no deaths. The paper opens with "Zenagamtide (formerly amycretin)" and describes it as a unimolecular agonist of GLP-1, amylin and calcitonin receptors.

Participants / model
262 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor (HbA1c 7.0 to 10.0%, BMI 23.0 to under 50.0), at 83 sites in 11 countries
Treatment
Subcutaneous zenagamtide once weekly at six doses (0.4, 1.5, 5, 10, 20 or 40 mg; 225 participants) or placebo (37)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial (NCT06542874); efficacy estimand
Funding
Novo Nordisk funded

The abstract gives no weight results; those appear only in a company release. The authors describe calcitonin receptor activity, which the WHO descriptor does not name.

Read the original source
Oral phase 2 in type 2 diabetes: 186 adults, 36 weeks, HbA1c change -0.9% to -1.4%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):607-620. PMID 42532079.

Estimated HbA1c change was -0.9% at 6 mg (difference versus placebo -0.5%, 95% CI -1.04 to -0.04), -1.3% at 25 mg (-0.99%, -1.49 to -0.49) and -1.4% at 50 mg (-1.09%, -1.59 to -0.59). Gastrointestinal adverse events occurred in 14 (26%) of 54, 21 (41%) of 51 and 24 (47%) of 51, versus 7 (23%) of 30 on placebo. Serious adverse events occurred in 7 (4%) of 186 participants, none on placebo, with no deaths.

Participants / model
186 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor
Treatment
Oral tablets once daily: 6 mg (54), 25 mg (51), 50 mg (51) or placebo (30)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial, same 36-week design and sites as the subcutaneous trial (NCT06542874)
Funding
not stated in the source

The abstract gives no weight results. The Lancet papers describe amycretin as zenagamtide, formerly amycretin.

Read the original source
Subcutaneous phase 1b/2a: 125 adults, weight change -24.3% at 60 mg versus -1.1% on placebo, heavy dropout

Randomized controlled trial

Dahl K et al. Lancet. 2025;406(10499):149-162. PMID 40550231.

Estimated mean weight change versus placebo was -24.3% versus -1.1% at 60 mg (week 36), -22.0% versus 1.9% at 20 mg (week 36), -16.2% versus 2.3% at 5 mg (week 28) and -9.7% versus 2.0% at 1.25 mg (week 20). The arms ran for different lengths and were not compared with each other. Gastrointestinal events were most common and mostly mild to moderate. The abstract says a large number of participants withdrew, many for reasons unrelated to adverse events, and gives no count.

Participants / model
125 adults aged 18 to 55 with overweight or obesity (BMI 27.0 to 39.9) at one US site; 101 on amycretin and 24 on placebo
Treatment
Subcutaneous amycretin once weekly, or placebo
Follow-up
20 to 36 weeks depending on the dose arm
Study design
Randomized phase 1b/2a trial (NCT06064006)
Funding
not stated in the source

Single-site, small, and sponsor-affiliated: 10 of the 12 authors list Novo Nordisk affiliations. The dropout count is not in the abstract.

Read the original source
Company statement, 25 November 2025: weight down by up to 14.5% subcutaneous and 10.1% oral at week 36

Clinical trial

Novo Nordisk A/S. Company Announcement No 38 / 2025, dated 25 November 2025, which uses the name amycretin.

The company reported that in 448 people with type 2 diabetes, weight fell by up to 14.5% on subcutaneous dosing (baseline 99.2 kg) versus 2.6% on placebo, and by up to 10.1% on oral dosing (baseline 101.1 kg) versus 2.5% on placebo, at week 36. The release notes that the top subcutaneous dose had only 4 weeks at maintenance. The release and the Q1 2026 slide give HbA1c falls of up to 1.8 points subcutaneous and 1.5 oral.

Participants / model
448 adults with type 2 diabetes
Treatment
Subcutaneous once weekly and oral once daily
Follow-up
Week 36
Study design
Company announcement of a randomized phase 2 trial; not peer reviewed
Funding
not stated in the source

These are best-dose up-to figures from the company. The Lancet efficacy-estimand HbA1c figure for the top subcutaneous dose is -1.7%, against the company's up-to 1.8 points.

Read the original source
Registry, 10 October 2026: 31 records, 15 phase 3, none with results

Trial registry record

ClinicalTrials.gov search run on 10 October 2026 for zenagamtide, amycretin or NNC0487-0111, with AMAZE 1 (NCT07339423) as the reference record.

The search returned 31 records, 15 of them phase 3, none with results posted. Examples: AMAZE 1 (NCT07339423, subcutaneous versus placebo, 1,150 estimated, started 24 February 2026, weight change to week 84); AMAZE 9 (NCT07720271, oral versus placebo, 950 estimated, started 31 August 2026, weight change to week 76); AMAZE 7 (NCT07668414, versus semaglutide, 650 estimated, started 22 September 2026); AMBITION 7 (NCT07797335, type 2 diabetes versus insulin glargine, 1,778 estimated, started 24 August 2026, HbA1c non-inferiority at week 52); and AMBIENCE (NCT07861100, 8,500 estimated, not yet recruiting, listed start 26 October 2026, four-point MACE). A registration is not an outcome.

Participants / model
Adults with obesity, type 2 diabetes or cardiovascular disease (planned populations)
Treatment
Subcutaneous once weekly or oral once daily
Follow-up
Primary outcomes planned at weeks 52 to 84
Study design
Official trial registry
Funding
not stated in the source

Registrations and estimated sizes, not outcomes. No phase 3 results exist.

Read the original source
FDA record searches, 10 October 2026: no record or label; JAMA news item on unapproved sale

Regulatory record

Rubin R. JAMA. 2026. PMID 42853576.

openFDA Drugs@FDA returned no records for zenagamtide or amycretin (a pramlintide control returned NDA 021332), and DailyMed drug-name searches for both returned no labels. A JAMA Medical News article dated 9 October 2026 describes a black market for two unapproved GLP-1 drugs, retatrutide and zenagamtide. The EMA was not searched.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated regulator database search and news item
Funding
not stated in the source

Only the plain-language summary of the JAMA item was read. A search result shows what the databases returned on that date, and it is US-scoped.

Read the original source

Studies and sources

WHO Proposed INN List 133: GLP-1 and amylin receptors agonist

Regulatory record

World Health Organization. Proposed International Nonproprietary Names: List 133. WHO Drug Information, Vol. 39, No. 2, 2025.

Zenagamtide appears with the descriptor "glucagon-like peptide 1 (GLP-1) and amylin receptors agonist", molecular formula C343H550N94O116 and CAS 3005889-81-3. The chemical name describes a human GLP-1(7-37) variant (residues 1 to 31) fused through a G4 peptide linker to an artificial 33-peptide amylin receptor agonist (residues 36 to 68), 68-amide, with a fatty diacid side chain on lysine 31. The list prints neither the name amycretin nor any development code.

Participants / model
Chemical and regulatory description, not a clinical population
Treatment
Defined acylated peptide
Follow-up
Not applicable
Study design
WHO proposed INN list
Funding
not stated in the source

The list prints no former name or code, so the link between zenagamtide and amycretin rests on the Lancet papers and the company presentation. PubChem name lookups on 10 October 2026 returned no record, so no PubChem CID or molecular weight is given.

Read the original source
Subcutaneous phase 2 in type 2 diabetes: 262 adults, 36 weeks, HbA1c change -0.9% to -1.7%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):621-635. PMID 42532080.

From a mean baseline HbA1c of 7.8%, the estimated HbA1c change ranged from -0.9% at 0.4 mg (difference versus placebo -0.77%, 95% CI -1.26 to -0.28) to -1.7% at 40 mg (-1.56%, 95% CI -2.05 to -1.07), on the efficacy estimand (on-treatment data without rescue medication). Most adverse events were gastrointestinal and mild to moderate. Serious adverse events occurred in 21 (8%) of 261 exposed, three of them on placebo, with no deaths. The paper opens with "Zenagamtide (formerly amycretin)" and describes it as a unimolecular agonist of GLP-1, amylin and calcitonin receptors.

Participants / model
262 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor (HbA1c 7.0 to 10.0%, BMI 23.0 to under 50.0), at 83 sites in 11 countries
Treatment
Subcutaneous zenagamtide once weekly at six doses (0.4, 1.5, 5, 10, 20 or 40 mg; 225 participants) or placebo (37)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial (NCT06542874); efficacy estimand
Funding
Novo Nordisk funded

The abstract gives no weight results; those appear only in a company release. The authors describe calcitonin receptor activity, which the WHO descriptor does not name.

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Oral phase 2 in type 2 diabetes: 186 adults, 36 weeks, HbA1c change -0.9% to -1.4%

Randomized controlled trial

Mora P et al. Lancet. 2026;408(10555):607-620. PMID 42532079.

Estimated HbA1c change was -0.9% at 6 mg (difference versus placebo -0.5%, 95% CI -1.04 to -0.04), -1.3% at 25 mg (-0.99%, -1.49 to -0.49) and -1.4% at 50 mg (-1.09%, -1.59 to -0.59). Gastrointestinal adverse events occurred in 14 (26%) of 54, 21 (41%) of 51 and 24 (47%) of 51, versus 7 (23%) of 30 on placebo. Serious adverse events occurred in 7 (4%) of 186 participants, none on placebo, with no deaths.

Participants / model
186 adults aged 18 to 75 with type 2 diabetes on metformin with or without an SGLT2 inhibitor
Treatment
Oral tablets once daily: 6 mg (54), 25 mg (51), 50 mg (51) or placebo (30)
Follow-up
36 weeks
Study design
Randomized placebo-controlled phase 2 trial, same 36-week design and sites as the subcutaneous trial (NCT06542874)
Funding
not stated in the source

The abstract gives no weight results. The Lancet papers describe amycretin as zenagamtide, formerly amycretin.

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Oral phase 1: 144 adults, single and multiple ascending doses, no weight figures in the abstract

Randomized controlled trial

Gasiorek A et al. Lancet. 2025;406(10499):135-148. PMID 40550229.

There were 364 treatment-emergent adverse events in 89 (62%) of 144 participants, all mild or moderate and dose-dependent, and 180 (49%) of the 364 were gastrointestinal. There were no deaths. Plasma levels were consistent with dose proportionality. The abstract gives no weight figures.

Participants / model
144 adults aged 18 to 55 with overweight or obesity at one US site (BMI 25.0 to 34.9 in the single-dose and 10-day parts, 27.0 to 39.9 in the 12-week part)
Treatment
Oral tablets: single doses of 1 to 25 mg (48 participants), a 10-day part (36) and a 12-week part (60) escalating once-daily doses up to 50 mg or 2 x 50 mg
Follow-up
Single dose, 10 days and 12 weeks in three parts
Study design
Randomized phase 1 first-in-human trial, single and multiple ascending doses (NCT05369390)
Funding
not stated in the source

Exploratory weight and fasting glucose were secondary measures; the abstract reports neither.

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Subcutaneous phase 1b/2a: 125 adults, weight change -24.3% at 60 mg versus -1.1% on placebo, heavy dropout

Randomized controlled trial

Dahl K et al. Lancet. 2025;406(10499):149-162. PMID 40550231.

Estimated mean weight change versus placebo was -24.3% versus -1.1% at 60 mg (week 36), -22.0% versus 1.9% at 20 mg (week 36), -16.2% versus 2.3% at 5 mg (week 28) and -9.7% versus 2.0% at 1.25 mg (week 20). The arms ran for different lengths and were not compared with each other. Gastrointestinal events were most common and mostly mild to moderate. The abstract says a large number of participants withdrew, many for reasons unrelated to adverse events, and gives no count.

Participants / model
125 adults aged 18 to 55 with overweight or obesity (BMI 27.0 to 39.9) at one US site; 101 on amycretin and 24 on placebo
Treatment
Subcutaneous amycretin once weekly, or placebo
Follow-up
20 to 36 weeks depending on the dose arm
Study design
Randomized phase 1b/2a trial (NCT06064006)
Funding
not stated in the source

Single-site, small, and sponsor-affiliated: 10 of the 12 authors list Novo Nordisk affiliations. The dropout count is not in the abstract.

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Rats: 21 days, energy intake down 47%, body weight down 18%; receptor activation in cells

Animal study

Kuhre RE et al. EBioMedicine. 2025;118:105862. PMID 40706446.

In diet-induced obese rats, 21 days of amycretin cut total energy intake by 47% and body weight by 18% (95% CI of mean change from pre-treatment: vehicle 6.56 to 8.47% versus amycretin -10.48 to -12.74%) while maintaining energy expenditure. Insulin sensitivity improved on a hyperinsulinaemic euglycaemic clamp and liver steatosis fell. In cell-based systems it activated human, mouse and rat GLP-1, amylin and calcitonin receptors.

Participants / model
Diet-induced obese rats and mice; cell-based receptor assays
Treatment
Amycretin; route not stated in the abstract
Follow-up
21 days
Study design
Original preclinical study
Funding
not stated in the source

All authors are Novo Nordisk staff. The abstract states no route or dose. Rodent data do not transfer to people.

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Company statement, 25 November 2025: weight down by up to 14.5% subcutaneous and 10.1% oral at week 36

Clinical trial

Novo Nordisk A/S. Company Announcement No 38 / 2025, dated 25 November 2025, which uses the name amycretin.

The company reported that in 448 people with type 2 diabetes, weight fell by up to 14.5% on subcutaneous dosing (baseline 99.2 kg) versus 2.6% on placebo, and by up to 10.1% on oral dosing (baseline 101.1 kg) versus 2.5% on placebo, at week 36. The release notes that the top subcutaneous dose had only 4 weeks at maintenance. The release and the Q1 2026 slide give HbA1c falls of up to 1.8 points subcutaneous and 1.5 oral.

Participants / model
448 adults with type 2 diabetes
Treatment
Subcutaneous once weekly and oral once daily
Follow-up
Week 36
Study design
Company announcement of a randomized phase 2 trial; not peer reviewed
Funding
not stated in the source

These are best-dose up-to figures from the company. The Lancet efficacy-estimand HbA1c figure for the top subcutaneous dose is -1.7%, against the company's up-to 1.8 points.

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Novo Nordisk Q1 2026 presentation: oral NN9487 and subcutaneous NN9490 as separate programs

Regulatory record

Novo Nordisk A/S. Investor presentation for the first three months of 2026.

A slide is titled "Zenagamtide (amycretin) to advance to phase 3 in T2D", and a pipeline slide lists "NN9487 - Oral zenagamtide" and "NN9490 - Sc. zenagamtide" as separate entries. ClinicalTrials.gov matches: the oral first-in-human trial is NN9487-4830 (NCT05369390) and oral AMAZE 9 is NN9487-8023 (NCT07720271), while the subcutaneous phase 1b/2a is NN9490-7613 (NCT06064006) and AMAZE 1 is NN9490-8021 (NCT07339423). The combined oral and subcutaneous phase 2 diabetes trial (NCT06542874) is filed under NN9490-7678, and registry records use the intervention name NNC0487-0111.

Participants / model
Not a clinical population
Treatment
Not applicable
Follow-up
Q1 2026 presentation
Study design
Company statement plus trial registry matches
Funding
not stated in the source

NN9487 names the oral program only, so it is not used for the molecule as a whole. The slide gives HbA1c falls of up to 1.8 points subcutaneous and 1.5 oral.

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Registry, 10 October 2026: 31 records, 15 phase 3, none with results

Trial registry record

ClinicalTrials.gov search run on 10 October 2026 for zenagamtide, amycretin or NNC0487-0111, with AMAZE 1 (NCT07339423) as the reference record.

The search returned 31 records, 15 of them phase 3, none with results posted. Examples: AMAZE 1 (NCT07339423, subcutaneous versus placebo, 1,150 estimated, started 24 February 2026, weight change to week 84); AMAZE 9 (NCT07720271, oral versus placebo, 950 estimated, started 31 August 2026, weight change to week 76); AMAZE 7 (NCT07668414, versus semaglutide, 650 estimated, started 22 September 2026); AMBITION 7 (NCT07797335, type 2 diabetes versus insulin glargine, 1,778 estimated, started 24 August 2026, HbA1c non-inferiority at week 52); and AMBIENCE (NCT07861100, 8,500 estimated, not yet recruiting, listed start 26 October 2026, four-point MACE). A registration is not an outcome.

Participants / model
Adults with obesity, type 2 diabetes or cardiovascular disease (planned populations)
Treatment
Subcutaneous once weekly or oral once daily
Follow-up
Primary outcomes planned at weeks 52 to 84
Study design
Official trial registry
Funding
not stated in the source

Registrations and estimated sizes, not outcomes. No phase 3 results exist.

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Renal impairment study: 42 adults, exposure similar across groups

Clinical trial

Oldenburg LIK et al. Diabetes Obes Metab. 2026;28(10):8946-8954. PMID 42443140.

Geometric mean AUC0-inf was 520 to 715 h x nmol/L across impairment groups versus 543 h x nmol/L with normal function, and Cmax was 2.8 to 3.5 versus 3.2 nmol/L. Treatment-emergent adverse events occurred in 30 (71.4%) of the 42 participants, none serious or severe.

Participants / model
42 adults with BMI 20.0 to 39.9: 14 with normal renal function and 7 in each of four impairment groups, including end-stage renal disease
Treatment
Single 0.3 mg subcutaneous dose
Follow-up
Single dose
Study design
Clinical pharmacology study (NCT06559527)
Funding
not stated in the source

Novo Nordisk authors. The abstract gives no half-life or Tmax.

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Why is Amycretin in B tier?

B fits a drug with a consistent mechanism description and large early outcomes but no phase 3 result. Two randomized phase 2 diabetes trials appeared in The Lancet and a phase 1b/2a obesity trial showed large weight changes. The obesity data come from a small single-site trial with heavy, uncounted dropout, the diabetes weight data are company-reported, and there is no approval or long-term safety dataset.