What is amycretin?

Two hormones, one molecule

Every approved GLP-1 drug works on a single primary receptor. Semaglutide (Wegovy, Ozempic) targets GLP-1 only. Tirzepatide (Zepbound, Mounjaro) adds GIP, a second receptor, which amplifies the insulin response and has direct effects on fat cells. Retatrutide pushes further to a third receptor: glucagon, which raises the body's resting energy expenditure.

Amycretin takes a different direction. Instead of stacking metabolic receptors, it combines GLP-1 with amylin. Amylin is not a metabolic hormone in the same sense as GIP or glucagon. It is a satiety hormone, co-secreted with insulin from pancreatic beta cells at roughly a 100-to-1 ratio. Its job is appetite suppression, but through a pathway that does not overlap with GLP-1. That is the central claim: two separate circuits, one injection.

The technical name for this approach is a unimolecular dual agonist. GLP-1 and amylin analogs are covalently bonded into a single peptide chain rather than combined as two separate molecules. Compare that to CagriSema, which is a fixed-dose co-formulation of two distinct drugs: semaglutide and cagrilintide. Both reach the same two receptors. The engineering approach differs, and it may matter for dosing flexibility and how the two agonist effects are balanced.

What amylin actually does

GLP-1 signals satiety primarily through the hypothalamus, specifically the arcuate nucleus and adjacent regions that regulate energy balance. Amylin works further back in the brain, in the brainstem. It binds to receptors in the area postrema and nucleus tractus solitarius, two structures that process signals from the gut about meal size and composition.

From there, amylin activates POMC neurons, which reduce food intake, and suppresses NPY and AgRP circuits, which normally drive hunger. It also delays gastric emptying via vagal pathways, contributing to fullness. These are genuinely different neural populations from the ones GLP-1 activates.

The practical implication: combining them should produce additive effects, not redundant ones. That is what the early trials suggest.

What the Phase 2 data showed

The Phase 1b/2a trial enrolled 125 adults with overweight or obesity at a single site in San Antonio, Texas. It was small. But the numbers were striking. At the highest subcutaneous dose tested (60mg), participants lost 24.3% of their body weight by week 36 versus 1.1% for placebo. At 20mg, weight loss was 22.0% at week 36.

The curve had not plateaued at week 36 for any dose. Weight loss was still proceeding. That is the same pattern Novo Nordisk noted with semaglutide early in development, and with cagrilintide, the amylin component of CagriSema: these drugs tend to show continued response over time in ways that many earlier anti-obesity compounds did not.

For context: tirzepatide produced 20.9% weight loss in its SURMOUNT-1 Phase 3 trial at 72 weeks. Semaglutide 2.4mg produced 14.9% at 68 weeks. Amycretin's 24.3% from Phase 2 is numerically better, but Phase 2 trials are small, often run at single sites, and typically enroll motivated populations. Phase 3 numbers in broader populations routinely come in lower than Phase 2 showed. The AMAZE trials will tell us how durable and generalizable this is.

New ADA 2026 data: the diabetes picture

At the ADA Scientific Sessions in June 2026, Novo Nordisk presented Phase 2 data on zenagamtide in adults with type 2 diabetes. The trial enrolled 262 adults with T2D inadequately controlled on metformin with or without an SGLT2 inhibitor.

The highest dose (40mg) cut HbA1c by 1.71 percentage points from a baseline of 7.8%. 89.1% of participants at that dose reached A1C below 7%, and 76.2% reached 6.5% or below. Weight loss in the T2D population reached 14.6% at the 40mg dose, versus 2.1% for placebo.

No plateau was observed by the end of the 36-week study. Phase 3 for the T2D indication is planned to begin in the second half of 2026.

The oral form

Amycretin is in development as both a weekly subcutaneous injection and an oral daily tablet. The oral version uses salcaprozate sodium (SNAC) as a permeation enhancer, the same technology that makes Rybelsus (oral semaglutide) absorbable. Peptides cannot cross the gut wall without chemical assistance.

In a 12-week obesity study, the oral form produced roughly 13% weight loss at the highest dose. That is less than the injectable form at comparable time points. It is also more than oral semaglutide (Rybelsus) produces in typical use, though the comparison is not direct since the populations and durations differed. A 36-week oral diabetes trial showed 10.1% weight loss and 1.5 percentage points of HbA1c reduction.

Oral GLP-1 drugs are not inherently less effective than injections, but the absorption hurdles require different dose management. Orforglipron, a non-peptide oral GLP-1 approved in 2026 as Foundayo, avoids the SNAC limitation entirely by using a small molecule rather than a peptide. For more on how oral drugs in this class compare, see oral semaglutide vs orforglipron.

How amycretin compares to tirzepatide and retatrutide

These three drugs are aiming at the same problem from different angles.

Tirzepatide (GLP-1 + GIP) works by amplifying the insulin response and acting directly on fat cells through GIP receptors. It is the best-performing approved drug in the class, at roughly 21% weight loss in Phase 3. Retatrutide adds glucagon to that mix, raising resting energy expenditure. TRIUMPH-1 showed 28.3% weight loss at 80 weeks.

Amycretin (GLP-1 + amylin) takes the satiety side rather than the metabolic side. Instead of increasing energy burning, it works on two brain circuits that suppress hunger. Phase 2 showed 24.3%, which would place it between tirzepatide and retatrutide if Phase 3 confirms it, but Phase 2-to-Phase 3 slippage is real. Whether amylin's additive effect survives in a broader population is what AMAZE will answer.

None of this is a direct head-to-head comparison. Different trials, different populations, different durations. For the current options, see retatrutide vs tirzepatide.

The AMAZE Phase 3 program

The AMAZE Phase 3 program started enrolling in February 2026. The trials span multiple indications:

• AMAZE-1: obesity (started Feb 2026, 84-week primary endpoint, ~1,150 participants)
• AMAZE-2: obesity with type 2 diabetes
• AMAZE-3 and AMAZE-4: obesity with sleep apnea
• AMAZE-5 and AMAZE-6: obesity with knee osteoarthritis
• AMAZE-12: weight loss maintenance

AMAZE-1 is the lead obesity trial. At 84 weeks per participant plus enrollment and data analysis time, the earliest meaningful Phase 3 results would be late 2027 or early 2028. FDA review then adds 10 to 12 months. A realistic approval window is 2029 at the optimistic end.

Side effects: what Phase 2 showed

GI adverse events are the pattern across GLP-1 drugs, and amycretin follows that pattern, more intensely. In Phase 1b/2a, nausea was reported by 82% of treated participants. Vomiting occurred in 53%. Diarrhea in 41%. These numbers are meaningfully higher than what tirzepatide or semaglutide produce in their trials.

The events were dose-dependent and concentrated during the up-titration phase, which is expected. They diminished after dose stabilization. Nearly all were classified as mild to moderate in severity. No unexpected organ-level toxicity appeared.

The key question for Phase 3 is whether the GI burden in a broader, longer trial translates to higher discontinuation rates. Phase 2 trials, especially single-site ones with motivated participants, typically underestimate the dropout rates seen in the real world. GI tolerability has been a meaningful factor in adherence for every GLP-1 drug.

What this means now

Amycretin is not available. There is no legal route to access it outside of a clinical trial. What it represents is a plausible next step in obesity pharmacology, one that attacks the satiety problem from the brain-circuit side rather than by stacking metabolic hormones.

If Phase 3 validates what Phase 2 showed, the obesity drug landscape in 2030 will look quite different from today: retatrutide approaching 28 to 30% weight loss, amycretin potentially in the same range through a different mechanism, and CagriSema (a structurally similar but less advanced approach) in between. For what is available today and how those drugs compare, see semaglutide vs tirzepatide.