Amycretin: Novo Nordisk's GLP-1/Amylin Co-Agonist Evidence Reviewed (2026)

Last updated: June 2026

Medical disclaimer: This article is for informational purposes only and is not medical advice. Amycretin is an investigational drug and is not FDA-approved as of 2026. Do not start, stop, or change any treatment based on what you read here. Consult your doctor.

Amycretin is Novo Nordisk's next-generation weight-loss drug. It is a single molecule that turns on two appetite pathways at once, and it comes in both a weekly shot and a daily pill.

This review pulls the real numbers from the 2025 Lancet Phase 1 papers and Novo Nordisk's own readouts. Every figure is cited to a primary source.

Amycretin sits in a crowded but fast-moving pipeline. You can see how it stacks up against rivals in our next-gen GLP-1 pipeline landscape.

What is amycretin and how does its dual mechanism work?

Amycretin is one molecule that activates both the GLP-1 receptor and the amylin receptor, which is why it is called a unimolecular co-agonist. Its research code is NN9487.

Most weight-loss drugs hit a single target. Semaglutide (Ozempic, Wegovy) acts on GLP-1 alone. Amycretin adds amylin, a second hormone that the pancreas releases after you eat (Lancet, 2025).

Here is what each pathway does. GLP-1 lowers appetite and slows how fast the stomach empties.

Amylin is the newer piece. It signals fullness through the brainstem and reinforces the feeling of having eaten enough.

The bet is that two appetite signals together beat one. Combining GLP-1 and amylin in a single molecule may push weight loss past what GLP-1 alone can reach (Novo Nordisk, 2025).

What makes amycretin unusual is that one peptide does both jobs. Other amylin-based combos, like CagriSema, use two separate molecules dosed together.

Amycretin comes in two forms. One is a once-weekly injection under the skin. The other is a once-daily tablet that uses a SNAC absorption helper, the same trick that makes oral semaglutide work (Lancet, 2025).

What did the Phase 1 trials show?

In the Phase 1b/2a subcutaneous trial, the top dose cut body weight by 24.3% at 36 weeks, while oral amycretin cut weight by up to 13.1% at 12 weeks in its Phase 1 study. Both results beat placebo by a wide margin.

Start with the shot. The subcutaneous Phase 1b/2a trial enrolled 125 adults with overweight or obesity and ran doses up to 60 mg over 36 weeks (Lancet, 2025).

At the highest dose, participants lost 24.3% of their body weight at 36 weeks, against just 1.1% on placebo. Lower maintenance doses also beat placebo across the board (Novo Nordisk, 2025).

Now the pill. The oral Phase 1 trial was a first-in-human study that ran single and multiple ascending doses, enrolling participants between May 2022 and January 2024 (Lancet, 2025).

Oral amycretin produced mean weight loss of 10.4% to 13.1% at 12 weeks, depending on the dosing regimen, versus about 1.2% on placebo. The 100 mg per day regimen reached the 13.1% figure (EurekAlert, 2025).

Here is the full trial picture, broken out by formulation, dose, and duration.

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Trial / cohort (year)	Formulation	Dose / duration	Sample (n)	Weight change
Phase 1b/2a (2025)	Subcutaneous	Up to 60 mg, 36 wk	125	-24.3% (placebo -1.1%)
Phase 1b/2a (2025)	Subcutaneous	20 mg maintenance, 36 wk	125	~-22% range
Phase 1 first-in-human (2025)	Oral	2 x 50 mg/day, 12 wk	144	-13.1% (placebo -1.2%)
Phase 1 first-in-human (2025)	Oral	50 mg/day, 12 wk	144	-10.4%
Phase 2 T2D (2026)	Subcutaneous	Top dose	undisclosed	-14.5% (placebo -2.6%)
Phase 2 T2D (2026)	Oral	Top dose	undisclosed	-10.1% (placebo -2.5%)

The subcutaneous weight-loss curve had not flattened at 36 weeks. That hints the true ceiling may be higher, which Phase 3 trials are now testing (Lancet, 2025).

A 2026 Phase 2 trial in type 2 diabetes added more data. The shot cut weight up to 14.5% and the pill up to 10.1%, with meaningful drops in A1C (Novo Nordisk, 2026).

How does amycretin compare to semaglutide and tirzepatide?

Amycretin's subcutaneous 24.3% loss at 36 weeks runs ahead of semaglutide and tirzepatide at similar time points, but these are cross-trial comparisons, not head-to-head data. No trial has pitted amycretin directly against either drug.

The numbers are striking. Semaglutide 2.4 mg (Wegovy) produced about 15% weight loss at 68 weeks in STEP-1. Tirzepatide (Zepbound) reached roughly 21% at 72 weeks in SURMOUNT-1.

Amycretin's 24.3% came in just 36 weeks, a shorter window. If that pace holds in longer trials, it could land among the strongest results in the class.

Here is the rough landscape, with the heavy caveat that durations and trials differ.

Drug	Mechanism	Best trial weight loss	Time point
Semaglutide (Wegovy)	GLP-1	~15%	68 wk
Tirzepatide (Zepbound)	GIP + GLP-1	~21%	72 wk
Amycretin (SC)	GLP-1 + amylin	24.3%	36 wk
Retatrutide	GIP/GLP-1/glucagon	24.2%	48 wk

These are not apples to apples. Amycretin's trial was small and early, while the semaglutide and tirzepatide figures come from large Phase 3 studies (Lancet, 2025).

For a closer look at the triple-agonist contender, see our retatrutide evidence review. The two drugs may end up as direct rivals at the top of the market.

The honest read is that amycretin looks promising on speed and depth of weight loss. But early-phase numbers shrink and shift as trials grow larger.

What is the difference between oral and subcutaneous amycretin?

The subcutaneous form is a once-weekly injection that produced larger weight loss (24.3%), while the oral form is a once-daily tablet with smaller but still strong results (up to 13.1%). Novo is advancing both.

The injection is dosed once a week, like Wegovy. It reached the biggest weight-loss numbers in trials so far.

The tablet is taken once a day on an empty stomach. It relies on a SNAC carrier to push the peptide across the gut lining, the same approach used for the oral semaglutide pill Rybelsus (Lancet, 2025).

Why pursue both? A daily pill is easier for people who dislike needles, and it can scale faster because it skips injection-device manufacturing.

The trade-off shows in the numbers. Oral amycretin's 13.1% at 12 weeks trails the shot's 24.3% at 36 weeks, though the time windows differ. Pill absorption is also less complete than injection.

This oral-versus-injectable question is reshaping the whole field. We dig into it for the broader class in our oral vs injectable GLP-1 guide.

Both forms appeared similarly safe and tolerable in trials, with no major difference in the side-effect type (American College of Cardiology, 2025).

What are the reported side effects so far?

The most common side effects are gastrointestinal: nausea, vomiting, and related stomach symptoms, and they rise with the dose. This matches the rest of the GLP-1 class.

In both the oral and subcutaneous Phase 1 trials, the most common treatment-emergent adverse events were mild-to-moderate GI symptoms (Lancet, 2025).

Severity tracked with dose. The faster and higher the dose climbed, the more GI events showed up (Lancet, 2025).

There is a reassuring pattern. Most of these symptoms had resolved by the end of treatment, which is typical for the class during dose titration.

Researchers reported that oral and subcutaneous amycretin were similarly safe and tolerated as GLP-1 single agonists. That means no new or unexpected safety signal at this early stage (American College of Cardiology, 2025).

The standard fix is slow dosing. Starting low and stepping up gives the gut time to adjust, which limits nausea (Lancet, 2025).

One honest limit. These were small, short trials. Rarer or longer-term side effects will only become clear once the larger Phase 3 program reports.

What is amycretin's development timeline and FDA status?

Amycretin is not FDA-approved. Novo Nordisk advanced both forms straight into Phase 3 for obesity in early 2026, with a separate Phase 3 diabetes program also planned for 2026. Approval is years away.

Novo skipped a separate Phase 2 obesity step and moved straight to Phase 3, based on the Phase 1 data plus regulator feedback (Novo Nordisk, 2025).

Here is the program status as of mid-2026.

Trial / program	Population	Status	Detail
AMAZE 1 (Phase 3)	Obesity / overweight	Started Feb 2026	~1,150 enrolled; NCT07339423
Phase 1b/2a	Overweight / obesity	Completed	SC; NCT06064006
Phase 2 T2D	Type 2 diabetes	Reported 2026	NCT06542874
Phase 3 T2D	Type 2 diabetes	Planned 2026	Both oral and SC forms

The lead obesity trial, AMAZE 1, began on February 24, 2026, and is set to enroll about 1,150 people. Its completion dates run into 2029 (ClinicalTrials.gov, 2026).

What does that mean for timing? With Phase 3 only starting in 2026 and completion years out, an FDA filing is unlikely before the late 2020s. Until then, amycretin stays investigational.

One caution. Because amycretin is not approved, any product sold today as "amycretin" is not an FDA-reviewed medicine. There is no approved supply, dose, or label.

The bottom line

Amycretin is one of the most-watched drugs in the obesity pipeline, and the early data explains why. A single molecule hitting GLP-1 and amylin produced 24.3% weight loss in 36 weeks by injection, and up to 13.1% in 12 weeks by pill.

Those numbers rival or beat approved drugs at similar points, though the trials were small and early. The side-effect profile so far looks like the familiar GLP-1 pattern, mostly GI and dose-driven.

The big caveat is stage. Phase 3 only started in 2026, so the real efficacy, safety, and durability picture is still years from being settled. Amycretin is not FDA-approved, and no head-to-head trial against semaglutide or tirzepatide exists yet.

Related Reading

• Retatrutide evidence review
• Next-gen GLP-1 pipeline landscape
• CagriSema vs tirzepatide vs retatrutide

Frequently asked questions

Is amycretin FDA-approved in 2026?

No. As of mid-2026, amycretin is investigational and not approved by the FDA for any use. Novo Nordisk advanced both the oral and subcutaneous forms into Phase 3 trials for obesity in early 2026, which means approval is still several years away.

How much weight do people lose on amycretin?

In the Phase 1b/2a trial, once-weekly subcutaneous amycretin cut body weight by 24.3% at 36 weeks at the top dose, versus 1.1% on placebo. The once-daily oral form produced up to 13.1% weight loss at 12 weeks (Lancet, 2025).

How is amycretin different from semaglutide?

Semaglutide acts on a single receptor, GLP-1. Amycretin is a single molecule that activates two receptors, GLP-1 and amylin, adding a second appetite-control pathway. In separate trials, amycretin's weight loss has run higher, though no head-to-head trial has been published.

What is the difference between oral and subcutaneous amycretin?

Subcutaneous amycretin is a once-weekly injection and produced larger weight loss in trials (24.3% at 36 weeks). Oral amycretin is a once-daily tablet using a SNAC absorption helper, with smaller but still strong results of up to 13.1% at 12 weeks.

What are the most common amycretin side effects?

Gastrointestinal symptoms are most common: nausea, vomiting, and related stomach issues. These were mostly mild to moderate, rose with the dose, and usually resolved by the end of treatment. Researchers found amycretin was similarly tolerated to other GLP-1 drugs (American College of Cardiology, 2025).

-- The GLP-1 Daily Team