Guides May 13, 2026

Amycretin: Novo Nordisk's Next-Generation Obesity Drug in Oral and Subcutaneous Phase 3

Amycretin is Novo Nordisk's unimolecular GLP-1 and amylin receptor agonist, now in Phase 3 for obesity in both oral and subcutaneous forms. Here is what the trial data actually show.

Amycretin is one of the most important obesity drugs in the Novo Nordisk pipeline.

Not because it is just “another GLP-1.”

And not because it has already won anything clinically.

It matters because it appears to combine several things the obesity market cares about at the same time:

GLP-1 biology
amylin biology
a single-molecule design
a weekly injectable formulation
and a daily oral formulation that Novo is moving forward in parallel

That combination makes amycretin more than a routine follow-on asset.

It looks much more like Novo Nordisk’s real post-CagriSema obesity strategy.

What amycretin is

Amycretin is an investigational unimolecular peptide agonist developed by Novo Nordisk under the code NNC0487-0111.¹²

That “unimolecular” wording matters.

Novo describes amycretin as a long-acting GLP-1 and amylin receptor agonist in a single molecule, developed for both:

once-weekly subcutaneous administration
and once-daily oral administration¹³

So unlike something like CagriSema, which combines semaglutide and cagrilintide as two separate active components, amycretin is trying to hit the same broad biology from one engineered peptide.

That is the core strategic idea.

Why amylin matters, not just GLP-1

GLP-1 is now familiar to almost everyone in obesity and diabetes discussions.

Amylin is not.

But it matters for understanding why amycretin is getting so much attention.

Amylin is a peptide hormone co-secreted with insulin by pancreatic beta cells. Reviews on amylin-targeted obesity therapy describe its main physiological roles as including:

slowing gastric emptying
reducing postprandial glucagon
and promoting satiety through central nervous system pathways⁴

That is a different signaling lane from GLP-1, even if the clinical output overlaps in appetite and weight regulation.

So amycretin is not simply “stronger semaglutide.”

It is better thought of as an attempt to combine incretin and amylin signaling into a single peptide platform.

The subcutaneous data are the reason the field took notice

The most important published obesity data so far come from the phase 1b/2a subcutaneous trial reported in The Lancet in June 2025.⁵

That study evaluated once-weekly subcutaneous amycretin in adults with overweight or obesity for up to 36 weeks.⁵

The signal was strong enough to immediately change how people talked about the drug.

The trial reported dose-dependent weight loss, with the commonly cited maintenance-dose results showing:

-9.7% at 1.25 mg over 20 weeks
-16.2% at 5 mg over 28 weeks
-22.0% at 20 mg over 36 weeks⁵

Placebo participants, by comparison, gained about 2% body weight in the 36-week comparison subgroup.⁵

That is already competitive territory.

And because some higher-dose escalation data in the same development program pushed the modeled maximum effect above those subgroup numbers, later summaries of the dataset often cite up to roughly 24% weight loss at the high end of the program.⁶

The safe way to summarize it is:

22% at the 20 mg, 36-week maintenance-dose subgroup
with broader program data suggesting even more weight loss may be possible at higher exposure

The oral data are what make the story bigger

If amycretin were only another injectable obesity drug, it would still matter.

But it is not.

The oral formulation is what makes the pipeline story much more interesting.

The first-in-human oral amycretin study, also published in The Lancet, evaluated single-ascending and multiple-ascending oral doses in adults with overweight or obesity.⁷

The trial used oral amycretin doses up to two 50 mg tablets daily and treatment durations up to 12 weeks.⁷¹

The headline figure people latched onto was that oral amycretin produced about 13.1% weight loss at 12 weeks at the highest dose, with placebo around 1.2–1.5% and oral semaglutide around 6% in the comparison framework discussed after publication.⁸⁶

That does not mean oral amycretin has already beaten every injectable competitor.

What it does mean is that an oral peptide candidate appears to have shown unusually strong early weight-loss potential.

That is a big deal.

The SNAC piece matters

The oral formulation is not just “the same peptide in a pill.”

The Lancet oral paper specifically notes that two different SNAC-based oral formulations of amycretin were evaluated in the study.⁷

SNAC, or sodium N-[8-(2-hydroxybenzoyl) amino] caprylate, is the same absorption-enhancer technology most people already associate with oral semaglutide.⁹

That matters because oral peptide delivery is hard.

So when Novo moves an oral peptide forward aggressively, it usually reflects more than marketing optimism. It reflects actual conviction about formulation feasibility.

The November 2025 type 2 diabetes readout made the story stronger

On November 25, 2025, Novo Nordisk reported positive phase 2 data for amycretin in 448 adults with type 2 diabetes inadequately controlled on metformin with or without an SGLT2 inhibitor.³

This was the first time amycretin had been evaluated in that population.

According to Novo’s filing:

subcutaneous amycretin achieved HbA1c reductions up to 1.8%
oral amycretin achieved HbA1c reductions up to 1.5%
subcutaneous amycretin achieved weight loss up to 14.5%
oral amycretin achieved weight loss up to 10.1%
and for higher doses, no weight-loss plateau was observed at week 36 irrespective of administration route³

That last point is one of the more important details in the whole program.

No plateau at week 36 does not guarantee dramatically larger long-term weight loss.

But it does support the idea that the 36-week obesity data may not yet represent the full ceiling of the molecule.

Phase 3 is not hypothetical anymore

On June 12, 2025, Novo Nordisk announced that it would advance both subcutaneous and oral amycretin into phase 3 development for weight management based on completed studies and regulatory feedback after end-of-phase interactions.¹

Novo said at the time that it planned to initiate the phase 3 weight-management program in Q1 2026.¹

By May 2026, ClinicalTrials.gov records show the amycretin phase 3 obesity program active under the AMAZE name, including:

AMAZE 12 for weight-loss maintenance after initial reduction¹⁰
HF-POLARIS, a phase 3 program evaluating NNC0487-0111 in people with heart failure and obesity¹¹

The full phase 3 map is still expanding, but the key strategic point is already clear:

Novo is not treating amycretin like a side project.

It is treating it like a major platform candidate.

Why the comparison to CagriSema is unavoidable

Amycretin and CagriSema are not the same thing.

But the comparison is still the right one.

CagriSema is Novo’s combination strategy:

cagrilintide for amylin biology
semaglutide for GLP-1 biology

Amycretin tries to reach a similar mechanistic destination in a single molecule.

That matters commercially and clinically.

If a single molecule can approach the efficacy of a dual-drug combination while preserving tolerability and making formulation simpler, that is a meaningful strategic advantage.

It is also one reason amycretin is often described as Novo’s likely next-generation Wegovy / post-CagriSema asset rather than just another obesity program sitting deeper in the pipeline.

The bottom line

Amycretin is important because it sits at the intersection of several high-value ideas in obesity pharmacology:

GLP-1 + amylin biology
single-molecule design
injectable and oral development in parallel
strong early efficacy
and large-company strategic commitment

The cleanest fair summary right now is:

amycretin is a real peptide, not a mislabeled small molecule
it is a unimolecular GLP-1 and amylin receptor agonist
the subcutaneous obesity data are strong
the oral data are unusually important
the type 2 diabetes phase 2 data reinforced the program
and phase 3 is now underway

That does not mean the outcome is settled.

Phase 3 still has to confirm:

durability
tolerability
discontinuation behavior
and whether early promise holds up against increasingly strong competition

But as of May 13, 2026, amycretin is one of the clearest names in the pipeline if you are trying to understand what Novo Nordisk thinks comes after the first wave of GLP-1 success.