Amycretin (zenagamtide)

Origin and structure

Novo Nordisk designed amycretin to do the work of two hormones with one molecule. One is GLP-1, the gut hormone that semaglutide imitates; the other is amylin, the hormone that the pancreas releases with insulin after a meal and that cagrilintide imitates. In CagriSema the company gives those two actions as two separate peptides. In amycretin they sit in a single chain.

That chain has 68 amino acids. The first 31 are a modified human GLP-1, with the unnatural amino acid 2-aminoisobutyric acid near the start so that the enzyme DPP-4 cannot break it down. A short linker of four glycines joins it to an artificial chain of 33 amino acids that acts on amylin receptors. A lysine at the end of the GLP-1 part carries a C18 fatty-acid side chain like semaglutide's, which binds to albumin in the blood and makes the molecule long-acting. Its average molecular weight is 7,847 daltons.

The first trial in people, of a tablet form, started in May 2022 at a clinic in San Antonio, Texas; the injected form followed in September 2023. During development it carried the code NNC0487-0111. In July 2025 the World Health Organization proposed zenagamtide as its international non-proprietary name (INN) and confirmed it as a recommended INN in 2026; Novo Nordisk has used that name, with amycretin as the former name, since early 2026.

How it works

Through its GLP-1 part, amycretin activates the GLP-1 receptor: it raises insulin release when blood glucose is high, lowers glucagon, slows the emptying of the stomach and reduces appetite. Through its amylin part it acts on amylin receptors, which are built from the calcitonin receptor paired with a helper protein (RAMP1, 2 or 3). Amylin slows stomach emptying, holds back glucagon after a meal and signals fullness to the brainstem.

In cell tests by Novo Nordisk, amycretin activated the human GLP-1 receptor about as potently as semaglutide, and it also activated all three amylin receptors and the calcitonin receptor itself, with negligible activity on related receptors for CGRP and adrenomedullin. The 2026 trial papers therefore describe it as an agonist of GLP-1, amylin and calcitonin receptors.

The other mechanistic data come from animals. In obese rats, three weeks of amycretin cut food intake by 47% and body weight by 10.8%, while untreated rats gained 7.5%, and the authors report that energy expenditure was maintained rather than falling as it usually does with weight loss. It also improved insulin sensitivity in rats and reduced liver fat in mice with diet-induced fatty liver disease, and in mice it reached appetite areas of the brainstem and hypothalamus. Whether any of this holds in people is still being tested; a study in Denmark and at Maastricht University, for example, measures energy expenditure after weight loss on amycretin, against a low-calorie diet and placebo.

Is amycretin approved?

No. No medicine containing amycretin is approved in the EU, the US or anywhere else. The EMA's list of new medicines under evaluation for October 2026 contains no application for it, and Novo Nordisk has not announced a filing with the FDA or said when it expects to file. In the Netherlands it is not a registered medicine, so it may not be sold or supplied for use in people. Products sold online under the names amycretin or zenagamtide are not Novo Nordisk's investigational medicine.

In sport, WADA class S0 prohibits at all times any substance that no other section of the list covers and that has no current approval for human therapeutic use, explicitly including drugs still in clinical development. Amycretin is not named on the list, but it falls under this class for as long as it is approved nowhere. The approved GLP-1-based medicines semaglutide and tirzepatide are permitted, which does not extend to an unapproved drug. In the Netherlands the Dopingautoriteit applies the same list.

People in the Netherlands take part in several of the trials. AMAZE 12 has five Dutch sites, in Almere, Amersfoort, Arnhem, Born and 's-Hertogenbosch; the heart-failure trial HF-POLARIS lists twenty Dutch hospitals and the cardiovascular trial AMBIENCE sixteen; and Maastricht University runs a phase 1 study of energy expenditure.

The phase 3 programme began in February 2026. By late October 2026, 15 phase 3 trials were registered on ClinicalTrials.gov, together planning to enrol more than 20,000 people, and ClinicalTrials.gov lists the first of them as finishing their main phase in mid-2028. The main trials:

• Weight management, injection (AMAZE): AMAZE 1 compares four weekly doses with placebo in 1,150 adults with obesity over 84 weeks, and AMAZE 2 does the same in 630 adults with overweight or obesity and type 2 diabetes. Further trials cover sleep apnoea (AMAZE 3 and 4), knee osteoarthritis (AMAZE 5 and 6), keeping weight off after a run-in phase (AMAZE 12, 606 participants), people in Japan and elsewhere in Asia (AMAZE 10 and 13) and two head-to-head comparisons with semaglutide (AMAZE 7 and 8).
• Weight management, tablet: AMAZE 9 started on 31 August 2026 and tests five once-daily doses against placebo in 950 adults in the US over 76 weeks.
• Type 2 diabetes: AMBITION 7 started on 24 August 2026 and compares weekly injections with daily insulin glargine in 1,778 adults at raised cardiovascular risk, with HbA1c at 52 weeks as the main outcome.
• Outcomes: HF-POLARIS (about 5,600 people with heart failure with preserved or mildly reduced ejection fraction and obesity, started May 2026, results expected in the second half of 2029) and AMBIENCE (8,500 people with atherosclerotic cardiovascular disease and overweight or obesity, registered in October 2026 and not yet recruiting).

What the research shows

All human data come from trials that Novo Nordisk designed and paid for. Results from three phase 1 and 2 trials, in four papers, have been published in The Lancet; no phase 3 trial has reported. The two obesity trials ran at a single clinic in Texas, had placebo groups of only four or five people per dose group and measured weight as a secondary or exploratory outcome, so their figures are early signals rather than settled effects.

• Tablet, phase 1 (Gasiorek et al., Lancet 2025): 144 adults with overweight or obesity. In the 12-week part, with 60 participants, weight fell 10.4% on 50 mg a day and 13.1% on two 50 mg tablets a day, against 1.2% on placebo. The main aim was safety, not weight loss.
• Injection, phase 1b/2a (Dahl et al., Lancet 2025): 125 adults with overweight or obesity, 101 of them on amycretin. Weight fell 9.7% after 20 weeks on 1.25 mg, 16.2% after 28 weeks on 5 mg, 22.0% after 36 weeks on 20 mg and 24.3% after 36 weeks in the group escalated to 60 mg, while the small placebo groups changed between −1.1% and +2.3%. Weight was still falling when treatment ended. Of the 101 people in the multiple-dose parts, placebo groups included, 40 withdrew from the study, 16 of them because of side effects.
• Injection in type 2 diabetes, phase 2 (Mora et al., Lancet 2026): 262 adults on metformin, with or without an SGLT2 inhibitor, at 83 sites in 11 countries, for 36 weeks. From an average of 7.8%, HbA1c fell 0.9 points on 0.4 mg up to 1.7 points on 40 mg, 1.56 points more than placebo. Weight fell up to 14.6% on 40 mg, 12.5 points more than placebo, although that group had been on its full dose for only the last four weeks.
• Tablet in type 2 diabetes, phase 2 (Mora et al., Lancet 2026): 186 adults in the same trial. HbA1c fell 0.9, 1.3 and 1.4 points on 6, 25 and 50 mg a day, 0.5 to 1.09 points more than placebo. Novo Nordisk reported weight loss of up to 10.1%, against 2.5% on placebo.
• Still running besides phase 3: smaller studies in Germany on appetite and insulin sensitivity, the Maastricht study on energy expenditure, and two US studies, started in October 2026, of switching to amycretin from semaglutide or tirzepatide.

Side effects and warnings

The side effects are mainly gastrointestinal, rise with the dose and are worst while the dose is being raised. In the injected obesity trial, 94% of participants on 5, 20 or 60 mg had a gastrointestinal side effect, and 63% on 1.25 mg; nausea affected 50% to 82% and vomiting 25% to 53%, depending on the group. Decreased appetite and headache were also common. The placebo groups, of four or five people per part, were too small for a fair comparison. Side effects led 6 of 17 people on 60 mg (35%) and 7 of 34 on 20 mg (21%) to withdraw.

In the type 2 diabetes trial with injections, nausea affected 11% on 0.4 mg up to 50% on 20 mg, against 14% on placebo, and vomiting and diarrhoea reached 29% and 37% on 40 mg, against 6% each on placebo. A third of the people on 20 or 40 mg (34%) stopped treatment because of side effects, against 6% on placebo. Abnormal skin sensations such as tingling (dysaesthesia), also seen with high-dose semaglutide, were reported by 21% on 40 mg and by no one on placebo. Serious adverse events were as frequent as on placebo (8%), and there was one case of severe low blood sugar. With tablets, gastrointestinal side effects affected 26% to 47%, against 23% on placebo, and 4% had a serious adverse event, against none on placebo. No deaths occurred in either part.

What is not known: no one has taken amycretin for longer than 36 weeks in a published trial, there are no data on heart or other outcomes, and without approved product information there is no official list of warnings. The trials so far were too small and too short to detect rare effects such as the pancreatitis and gallbladder disease listed for approved GLP-1 medicines; the phase 3 programme is meant to answer that.

Amycretin versus CagriSema and semaglutide

CagriSema, also from Novo Nordisk, reaches the same two receptor families with two molecules, cagrilintide and semaglutide, injected together once a week. It is a stage further: in the phase 3 trial REDEFINE 1, with 3,417 adults, those on the combination lost 20.4% of their body weight over 68 weeks against 3.0% on placebo, and it awaits an FDA decision. Amycretin puts both actions in one peptide and is also being developed as a daily tablet.

Setting amycretin's early figures next to those of CagriSema or semaglutide is misleading. The 22.0% and 24.3% came from 34 and 17 people at one clinic after 36 weeks, against placebo groups of five, whereas the headline figures for semaglutide (STEP 1) and CagriSema (REDEFINE 1) come from phase 3 trials with about 2,000 and 3,400 participants followed for 68 weeks. Direct answers are on the way: AMAZE 7 compares amycretin with two doses of semaglutide in 650 adults with overweight or obesity, and AMAZE 8 with semaglutide in 1,000 adults who also have type 2 diabetes, both over 84 weeks; Novo Nordisk expects AMAZE 8 to report in the first half of 2029.

Frequently asked questions

Are amycretin and zenagamtide the same thing?

Yes. Zenagamtide is the international non-proprietary name that the World Health Organization proposed for amycretin in July 2025 and confirmed as a recommended name in 2026. Novo Nordisk has used it since early 2026. Older papers and news use amycretin, and trial records often use the code NNC0487-0111. All three refer to the same molecule.

Is amycretin approved, and when will it be available?

It is not approved anywhere. Phase 3 trials began in February 2026, and ClinicalTrials.gov lists the first of them as finishing their main phase in mid-2028, with the large heart trials running into 2029 and 2030. Novo Nordisk has not said when it will apply for approval in the EU or the US.

How much weight do people lose on amycretin?

In the small injection trial in adults with overweight or obesity, weight fell 9.7% to 24.3% depending on dose and duration, the highest figure after 36 weeks in 17 people. With tablets, 13.1% after 12 weeks on the top dose. People with type 2 diabetes lost up to 14.6% with injections and up to 10.1% with tablets over 36 weeks. No phase 3 results exist yet.

Can you get amycretin in the Netherlands?

Only within clinical trials. It is not a registered medicine, so no doctor can prescribe it and no pharmacy can supply it. Dutch sites take part in AMAZE 12 and the heart-failure trial HF-POLARIS, and Maastricht University runs a smaller study. Products sold online as amycretin or zenagamtide are not Novo Nordisk's investigational medicine and may not be used in people.

Is amycretin banned in sport?

Yes, at all times. It is not named on the WADA Prohibited List, but class S0 prohibits any substance that no other section covers and that has no current approval for human therapeutic use, including drugs in clinical development. Approved GLP-1 agonists such as semaglutide are permitted, but that does not cover amycretin while it is approved nowhere. The Dutch Dopingautoriteit applies the same list.

What is the difference between amycretin and CagriSema?

Both come from Novo Nordisk and act on GLP-1 and amylin receptors. CagriSema is two molecules, cagrilintide and semaglutide, injected together once a week; amycretin is one molecule that does both, as a weekly injection or a daily tablet. CagriSema has phase 3 results and was filed with the FDA in December 2025; amycretin's phase 3 trials started in 2026. No trial compares the two directly.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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