Amycretin is the drug Novo Nordisk is betting on after CagriSema — and as of 2026 it has a new name. The two phase 2 papers published in The Lancet on 15 August 2026 call it zenagamtide (formerly amycretin); Novo's trial registrations still mostly use its code, NNC0487-0111. This page reads everything published and registered for the molecule under all three names, as of 27 September 2026. It is not approved anywhere.
For the two-molecule predecessor see CagriSema; for Lilly's triple agonist, retatrutide; for why adding a second hormone to GLP-1 is not straightforward, GIP and GLP-1.
What it is
GLP-1 drugs such as semaglutide act on one receptor. Amylin is a second gut-and-pancreas hormone involved in fullness; its receptors are built from the calcitonin receptor plus a partner protein, which is why the 2026 papers describe zenagamtide as an agonist of "GLP-1, amylin, and calcitonin receptors". Novo already combines the two ideas in CagriSema — semaglutide plus the amylin analogue cagrilintide, two molecules in one pen. Amycretin puts both actions into one molecule, which is also what makes a tablet version possible.
| Amycretin / zenagamtide | CagriSema | |
|---|---|---|
| Molecules | one | two (semaglutide + cagrilintide) |
| Forms tested | weekly injection; daily tablet | weekly injection |
| Stage (Sept 2026) | phase 3 started 2026 | filed with the FDA, December 2025 |
| Head-to-head registered against | semaglutide | tirzepatide (REDEFINE 4, lost) |
The obesity results so far
Only two obesity studies have been published, both early-phase, both at one clinical research centre in San Antonio, Texas, both funded by Novo Nordisk (The Lancet, 12 July 2025).
Weekly injection, phase 1b/2a (NCT06064006; 125 people randomised, 101 to amycretin and 24 to placebo):
| Part | Maintenance dose | Weeks | Amycretin | Placebo |
|---|---|---|---|---|
| B | 60 mg | 36 | −24.3% | −1.1% |
| C | 20 mg | 36 | −22.0% | +1.9% |
| D | 5 mg | 28 | −16.2% | +2.3% |
| E | 1.25 mg | 20 | −9.7% | +2.0% |
These are the numbers behind the "22%" in most headlines. Three things sit beside them in the same abstract: each dose group was small (the 24 placebo participants were spread across four parts); "a large number of participants withdrew", with many withdrawals for reasons unrelated to side effects; and the most common adverse events were gastrointestinal, mostly mild to moderate. Weight was a secondary endpoint — the study's primary purpose was safety.
Daily tablet, phase 1 (NCT05369390; 144 people): 62% of participants had an adverse event, all mild or moderate and increasing with dose, and 49% of the 364 events were gastrointestinal. The abstract reports weight change as an exploratory endpoint without giving the figure, so we do not quote one.
For comparison, and only loosely: semaglutide 2.4 mg produced about 15% over 68 weeks in its large phase 3 programme. A 36-week, single-site result and a 68-week, multinational one are not the same kind of evidence; the phase 3 head-to-heads below exist to settle that.
The 2026 diabetes trials
The two August 2026 Lancet papers report one phase 2 programme in people with type 2 diabetes on metformin (NCT06542874, 83 sites in 11 countries, 36 weeks). Their primary endpoint was blood sugar, measured as HbA1c:
| Form | Doses | HbA1c change (baseline ~7.8–8.1%) | Difference vs placebo | GI adverse events |
|---|---|---|---|---|
| Weekly injection (262 people) | 0.4 to 40 mg | −0.9 to −1.7 points | −0.77 to −1.56 | "most" events GI, mild–moderate |
| Daily tablet (186 people) | 6, 25, 50 mg | −0.9, −1.3, −1.4 points | −0.5, −0.99, −1.09 | 26%, 41%, 47% vs 23% placebo |
Serious adverse events: 21 of 261 (8%) across the injection study, spread through every dose and including 3 on placebo; 7 of 186 (4%) on the tablet, none on placebo. No deaths. The abstracts do not report weight change, which the full papers carry as secondary outcomes.
The phase 3 programme
On 27 September 2026, ClinicalTrials.gov held 28 records for the molecule (searched as amycretin, zenagamtide and NNC0487-0111): 14 phase 3, 2 phase 2, 12 phase 1 — and none with results posted.
| Trial | People | Population | Comparator | Primary completion |
|---|---|---|---|---|
| AMAZE 1 | 1,150 | obesity | placebo | June 2029 |
| AMAZE 2 | 630 | obesity + type 2 diabetes | placebo | August 2028 |
| AMAZE 3 / 4 | 300 / 300 | obesity + sleep apnoea (without / with CPAP) | placebo | July / June 2028 |
| AMAZE 5 / 6 | 400 / 400 | obesity + knee osteoarthritis | placebo | August 2028 |
| AMAZE 7 | 650 | obesity | semaglutide | October 2028 |
| AMAZE 8 | 1,000 | obesity + type 2 diabetes | semaglutide | December 2028 |
| AMAZE 9 | 950 | obesity, daily tablet | placebo | June 2028 |
| AMAZE 10 / 13 | 400 / 400 | Japanese / Asian populations | placebo | February / January 2029 |
| AMAZE 12 | 606 | obesity, after reaching target dose in a run-in | placebo | June 2028 (earliest) |
| AMBITION 7 | 1,778 | type 2 diabetes + cardiovascular risk | insulin glargine | July 2028 |
| HF-POLARIS | 5,610 | heart failure (preserved or mildly reduced ejection fraction) + obesity | placebo | July 2029 |
Two things stand out in that register. The only active comparator for weight is semaglutide — Novo's own drug — so no registered trial will show how zenagamtide compares with tirzepatide, the drug CagriSema lost to. And AMAZE 12 enrols only people who reach the target dose during a run-in period, a design that tests the drug in those who tolerate it; its result will read differently from a trial counting everyone randomised.
What is not known
- Long-term effects. The longest completed exposure in a published study is 36 weeks.
- Lean mass. No published study reports body composition; how much of the loss is muscle, a question for every drug in this class, is open. The approved drugs' record is on GLP-1 muscle loss.
- Dose for any future label. Phase 1/2 tested 0.4 mg to 60 mg by injection and up to 100 mg a day by tablet; no dose has been chosen publicly. Per-compound dosing is not covered on this site.
- Price and timing. No filing has been announced, so there is no price and no approval date.
This page reports trial records and does not recommend any medicine. The approved options, and how they compare today, are on best GLP-1 for weight loss and the GLP-1 drug list.
Sources
- Mora P et al. Once-weekly subcutaneous zenagamtide in type 2 diabetes: phase 2. Lancet 2026;408:621–635. doi:10.1016/S0140-6736(26)01248-1.
- Mora P et al. Once-daily oral zenagamtide in type 2 diabetes: phase 2. Lancet 2026;408:607–620. doi:10.1016/S0140-6736(26)01247-X.
- Amycretin subcutaneous phase 1b/2a (NCT06064006) and oral phase 1 (NCT05369390), Lancet 12 July 2025 (PubMed 40550231, 40550229).
- ClinicalTrials.gov, search "amycretin OR zenagamtide OR NNC0487-0111", 27 September 2026 — records NCT07339423, NCT07533175, NCT07571005, NCT07571109, NCT07481630, NCT07509307, NCT07668414, NCT07400107, NCT07720271, NCT07822061, NCT07668401, NCT07503210, NCT07797335, NCT07567001.