Amycretin

CInvestigational (early phase)GLP-1 and incretin agonists →Zenagamtide (INN)GLP-1 and amylin co-agonistunimolecular GLP-1/amylin receptor agonist
In one paragraphAmycretin is a single molecule that activates both the GLP-1 and the amylin receptor, combining the two mechanisms that CagriSema delivers as two drugs. Its international name is now zenagamtide. In the first published trial — a phase 1b/2a study in 125 people — the highest dose produced 24.3% weight loss at 36 weeks: the largest figure reported for any weight-loss drug at this stage, from a small, early trial in which many participants withdrew. Two phase 2 trials in type 2 diabetes, published in The Lancet in 2026, add a dose-dependent HbA1c reduction of up to 1.7 points; the weight-loss figure has not yet been repeated in a larger trial.
Overall gradeC Weak
Human trials1 phase 1b/2a RCT (n=125); 2 phase 2 RCTs in type 2 diabetes
Outcomes graded4
Last reviewed23 September 2026
EvidenceWhat it isHow it worksUnknownsMolecule & PKRegulationQuestionsReferences

What the human research shows

The headline weight number is extraordinary and the evidence behind it is thin — a first-in-class early-phase study, not an efficacy trial. The glycaemic effect now has a published phase 2 behind it. Grade C reflects the stage of the weight-loss evidence, not scepticism about the mechanism.

MetabolicCardioMuscleHealingNeuroImmuneSexualSkinAgeing

Evidence profile0–5

  • Metabolic & weightB3.5
  • Cardiovascular—0.0
  • Muscle & growth—0.0
  • Healing & repair—0.0
  • Neuro & sleep—0.0
  • Immune & inflammation—0.0
  • Sexual & hormonal—0.0
  • Skin & appearance—0.0
  • Ageing & longevity—0.0
Each score is confidence × effect size, taken from the best-evidenced benefit in that domain: the grade (A–D) sets the confidence, the measured effect sets the size. Hover a domain to see the outcomes behind it. Adverse effects are excluded and listed separately below.
OutcomeGradeEffect sizeHuman studiesWhere the evidence comes from
Body weightCWeakLarge1 phase 1b/2a RCT (n=125)Doses were escalated over 20–36 weeks. At the top 60 mg dose, weight fell 24.3% against 1.1% on placebo. Substantial numbers of participants withdrew, mostly for reasons unrelated to side effects, which limits how much weight the figure carries.1
Blood glucose (HbA1c) in type 2 diabetesBProbableLarge1 phase 2 RCT (n=262); oral companion trialA 36-week dose-finding trial of the weekly injection in adults with type 2 diabetes on metformin. HbA1c fell by 0.9 to 1.7 points across six doses, against placebo. A once-daily oral formulation was tested in a parallel trial. Both published in The Lancet, 2026.23
Trial retentionadverseCWeakModerate1 phase 1b/2a RCTThe trial reports a high withdrawal rate. Because dropouts were largely for reasons unrelated to adverse events, the remaining participants may not represent everyone who started — the standard caution for an early-phase efficacy figure.1
GI side effectsadverseCWeakModerate1 phase 1b/2a RCTGastrointestinal events were frequent, as with every drug in this class, and mostly resolved.1
AMultiple good human trials, consistentBSome human trials, mostly consistentCFew or weak human studiesDAnimal or anecdotal onlyeffect size · red = adverse

Literature searched to 23 September 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.

What it is

Amylin is a hormone released with insulin that signals fullness; GLP-1 does related work through a different receptor. Combining them is the idea behind CagriSema, which uses two separate molecules. Amycretin does both jobs with one.

It is a Novo Nordisk investigational compound, given the international non-proprietary name zenagamtide in 2026. The subcutaneous phase 1b/2a study and two phase 2 trials in type 2 diabetes (one weekly injection, one daily tablet) are published; phase 3 trials are in progress.

How it is thought to work

One peptide backbone carries agonist activity at both the GLP-1 and the amylin receptor, so appetite is suppressed through two pathways at once. Whether that produces more weight loss than the two given separately has not been tested head to head.

What is still unknown

  • Whether the 24% figure survives a properly powered phase 3 with full retention.
  • How it compares with CagriSema, tirzepatide or retatrutide — no head-to-head exists.
  • Everything about long-term safety; the published trials ran 36 weeks at most.

The molecule and how long it lasts

Identity

No PubChem Compound record at review (investigational; zenagamtide)

Pharmacokinetics
Route
Subcutaneous once weekly and oral once daily in the trials
Half-life
Dose-proportional exposure reported; no half-life figure in the accessible abstracts

From a published human pharmacokinetic study: Gasiorek A, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist amycretin: a first-in-human phase 1 trial. Lancet 2025;406:135–148

Regulatory status

European Union
Not authorised

Investigational; no EMA authorisation.

United States
Not approved

Investigational. Products sold under this name are not the trial drug.

United Kingdom
Not licensed

No MHRA licence.

Australia
Not on the ARTG

Investigational only.

Canada
Not authorised

No Drug Identification Number.

Sport (WADA)
Not prohibited

Not named on the 2026 Prohibited List.

Questions people actually ask

Is amycretin really better than tirzepatide?
Unknown. Its 24% figure comes from a phase 1b/2a trial in 125 people with heavy dropout; tirzepatide's 21% comes from a 2,539-person phase 3. Those are not comparable levels of evidence, and no head-to-head exists.
How is it different from CagriSema?
CagriSema is two molecules given together — cagrilintide plus semaglutide. Amycretin is one molecule doing both jobs.

One page per claimed effect

References

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Change log

  • 2026-09-23Name zenagamtide added. Two phase 2 trials in type 2 diabetes (Lancet, 2026) added with a verbatim primary result; new HbA1c row at B. Overall grade held at C: the weight-loss figure still rests on the 125-person early-phase trial.
  • 2026-09-03Initial publication from the phase 1b/2a Lancet report. Grade C for trial stage and retention.