Amycretin

What amycretin is

Amycretin is a drug from Novo Nordisk that targets two receptors at the same time: the one for GLP-1 and the one for amylin. Both are satiety signals, one from the gut, the other from the pancreas, reporting to the brain via two different channels. In the combination product CagriSema, these are still two separate substances in one injection. Amycretin packs both effects into a single molecule, like a key that fits two locks.

The idea behind amylin is not new. The amylin analog pramlintide has been approved in the US as a diabetes drug since 2005, but it had to be injected several times a day with meals and therefore hardly caught on. Amycretin brings back the same idea in a form that is injected once a week or taken daily as a tablet.

How it is supposed to work

The two channels work differently. GLP-1 dampens appetite, improves the insulin response and slows gastric emptying, which is also where the typical nausea comes from. Amylin acts in the brainstem on the end of a meal; it says less “don't eat” than “you're done”. The hope: two gentle signals instead of one at full blast.

In the laboratory, amycretin activates the human GLP-1, amylin and calcitonin receptors. In obese rats, it lowered energy intake by 47 percent and weight by 18 percent in 21 days without throttling energy expenditure, and it reached the brain regions that control eating behavior. In humans, the chain of action is clearly visible through weight and blood sugar.

Where it stands

In June 2025, Novo Nordisk announced that it would take the injection and the tablet into phase 3 for people with overweight. The drug now bears the name Zenagamtide, and the first phase 3 trials have been recruiting since August and September 2026: AMAZE 9 tests the tablet against placebo (NCT07720271), AMAZE 7 the injection in comparison with semaglutide (NCT07668414). In November 2025, the company also reported a phase 2 trial in type 2 diabetes with 448 participants: up to 14.5 percent weight loss with the injection versus 2.6 percent on placebo, up to 10.1 versus 2.5 percent with the tablet, and a reduction in the long-term blood sugar marker HbA1c of up to 1.8 percentage points. These numbers come from a company announcement; no full publication was available. In type 2 diabetes, AMBITION 7, a comparison of the injection with insulin glargine (NCT07797335), has been under way since August 2026. No results are available from any of these trials.

In context: pharma, not biohacking

Amycretin is classic pharmaceutical development, and that is a good sign. The side effects and trial discontinuations are reported openly in the same Lancet paper as the headline number, and the early data are followed by the regular approval program. The race is tight: Lilly is developing its own weight-loss tablet with orforglipron and a triple agonist with retatrutide; alongside amycretin, Novo Nordisk is betting on CagriSema.

The biohacking part of this story lies in everything around it. Anyone on such drugs who defends their muscles with strength training and enough protein, sleeps well and genuinely changes their diet has the best chance of keeping the result. Anyone interested in amycretin before it is approved will find ongoing trials in the public registries. That is the only way in which experimental and responsible go together.

What the studies show

Amycretin as an injection (Dahl, Lancet 2025)

In this phase 1b/2a trial at a single center in San Antonio, 125 adults with overweight or obesity were assigned to amycretin (101) or placebo (24), at several dose levels over 20 to 36 weeks. The primary endpoint was safety. Weight loss after 36 weeks was 24.3 percent at the highest level and 22.0 percent at the next lower one, versus 1.1 percent loss and 1.9 percent gain respectively on placebo. Even the lowest maintenance dose brought 9.7 percent after 20 weeks.

Amycretin as a tablet (Gasiorek, Lancet 2025)

The first trial in humans tested the tablet in a randomized, double-blind, placebo-controlled design in 144 participants. Adverse events occurred in 89 of them, that is, 62 percent, all mild or moderate and dose-dependent, mainly in the gastrointestinal tract. In the 12-week part of the trial, participants lost up to 13.1 percent.

Where the data stop

The much-quoted number comes from an early, small trial whose actual aim was safety. A third of participants, 33 percent, left early, with 59 percent of these discontinuations having nothing to do with side effects but rather with, for example, withdrawn consent or drug use. A direct comparison with semaglutide or tirzepatide is lacking, and whether the combination of two channels is better tolerated than GLP-1 alone is open. In the 2026 network meta-analysis, gastrointestinal complaints, nausea and vomiting were more frequent at high doses of the amylin-based therapies, notably also with the amycretin tablet. So the hope for two gentle signals has not yet been clearly confirmed in the early trials.

By definition, long-term data do not yet exist for an investigational drug; the longest treatment lasted 36 weeks. This means the course after stopping and the share of muscle mass in the weight loss are also unknown, both central questions for the entire drug class.

Status, approval and legal

Amycretin is not approved anywhere and is not available through regular channels. It is made only by Novo Nordisk and used in clinical trials; since August 2026, the first phase 3 trials have been under way under the name Zenagamtide. Approval is more likely toward the end of the decade. What is offered in online shops as amycretin is at best mislabeled and at worst an unknown peptide mixture. Anyone looking for medical help with weight loss today discusses approved options such as semaglutide or tirzepatide with their doctor. We do not give dosages for unapproved drugs.

Safety

The most common side effects affect the gastrointestinal tract, above all nausea and vomiting, dose-dependent and especially during dose escalation, mostly mild to moderate. In the injection trial, there was one case of recurrent pancreatitis caused by gallstones, and heart rate also rose. As with the entire drug class: rapid weight loss also costs muscle; enough protein, strength training and medical supervision are part of it. Long-term data are lacking.

Sources

• Dahl K et al., Lancet 2025
• Gasiorek A et al., Lancet 2025
• Kamrul-Hasan ABM et al., Endocrinol Diabetes Metab 2026
• Kuhre RE et al., EBioMedicine 2025
• Fu L et al., Metabolism 2026
• Bassatne A, Rizo I, Adv Ther 2026
• Walker CS et al., Nat Rev Endocrinol 2025
• Novo Nordisk, company announcement phase 2 type 2 diabetes, 2025-11-25
• Novo Nordisk, company announcement phase 3 obesity, 2025-06-12
• ClinicalTrials.gov, NCT07720271 (AMAZE 9, Zenagamtide tablet in overweight, phase 3)
• ClinicalTrials.gov, NCT07668414 (AMAZE 7, Zenagamtide compared with semaglutide, phase 3)
• ClinicalTrials.gov, NCT07797335 (AMBITION 7, Zenagamtide in type 2 diabetes, phase 3)