Amycretin: The Single Molecule Hitting Two Appetite Pathways at Once

What if one molecule could suppress your appetite through two independent pathways at the same time?

That is the question Novo Nordisk is trying to answer with amycretin, a single engineered molecule that activates both GLP-1 receptors and amylin receptors simultaneously. It is being developed as both a weekly injection and a daily oral pill, and the early clinical data has drawn attention for two reasons.

First, the injectable version produced 24.3% weight loss in just 36 weeks, and the weight loss curve had not plateaued. That is comparable to the best results from any obesity drug tested so far, including tirzepatide, and in roughly half the treatment time.

Second, the oral version produced 13.1% weight loss in just 12 weeks, also without plateauing. If that trajectory holds in longer trials, an oral weight loss pill could eventually match what injections deliver today.

Amycretin entered Phase 3 trials in early 2026. Here is what we know so far and what it could mean for patients.

How amycretin works

Amycretin is a unimolecular dual agonist, meaning it is a single engineered peptide that activates two different receptor systems at once. The two components are fused together into one molecule:

GLP-1 receptor activation reduces appetite, signals satiety to the brain, slows gastric emptying, and improves blood sugar control. This is the same pathway used by semaglutide (Wegovy/Ozempic) and tirzepatide (Mounjaro/Zepbound).

Amylin receptor activation provides a second, independent appetite suppression signal. Amylin is a hormone co-secreted with insulin from the pancreas after meals. It slows gastric emptying through a different mechanism than GLP-1, suppresses glucagon secretion, and signals satiety to the brain via distinct neural pathways.

The hypothesis is that activating both pathways at once produces additive or synergistic appetite suppression beyond what either pathway achieves alone.

How amycretin differs from CagriSema

Both amycretin and CagriSema target the same two receptor systems (GLP-1 and amylin). The difference is structural:

CagriSema physically mixes two existing drugs in one injection. Amycretin fuses the two activities into one engineered molecule. This single-molecule design may offer advantages in pharmacokinetics and manufacturing, and it makes an oral formulation possible, something CagriSema cannot do.

Clinical trial results

Injectable amycretin (Phase 1b/2a)

Published in The Lancet in June 2025, this trial enrolled 125 adults with overweight or obesity (BMI 27-39.9) and no diabetes. Participants received once-weekly subcutaneous injections across multiple dose groups.

The 24.3% weight loss at the highest dose is the standout number. But what made analysts pay attention was that the weight loss curve was still declining at 36 weeks without evidence of plateauing. Most obesity drugs reach a plateau by 40-50 weeks. If amycretin's trajectory continues, the final weight loss in Phase 3 (over 68+ weeks) could be higher still.

For comparison: semaglutide 2.4 mg (Wegovy) produced approximately 15% weight loss at 68 weeks in the STEP 1 trial. Amycretin reached 24% at 36 weeks and was still dropping.

Oral amycretin (Phase 1)

Also published in The Lancet in June 2025, this first-in-human trial enrolled 144 adults with overweight or obesity (BMI 25-34.9), no diabetes, and tested oral tablets over 12 weeks.

13.1% weight loss in just 12 weeks from an oral pill is notable. The weight loss had not plateaued at 12 weeks. To put this in perspective, oral semaglutide at the 25 mg dose (oral Wegovy) produced 13.6% weight loss at 64 weeks. Amycretin's oral formulation approached that number in roughly one-sixth the time.

Results in type 2 diabetes (Phase 2)

Novo Nordisk announced Phase 2 results in November 2025. The trial enrolled 448 adults with type 2 diabetes inadequately controlled on metformin.

At 36 weeks:
- Subcutaneous (best dose): 14.5% weight loss, HbA1c reduction of 1.8 percentage points
- Oral (best dose): 10.1% weight loss, HbA1c reduction of 1.5 percentage points
- 89.1% of subcutaneous participants achieved HbA1c below 7.0%

Weight loss in patients with type 2 diabetes is typically lower than in patients without diabetes. This pattern is consistent across all GLP-1 medications.

Side effects

The side effect profile is consistent with what you see across GLP-1 and amylin medications. The most common adverse events are gastrointestinal:

• Nausea (most frequent)
• Vomiting
• Diarrhea
• Decreased appetite

In the oral Phase 1 trial, 62% of participants had treatment-emergent adverse events, with 49% being gastrointestinal. Nearly all were mild to moderate.

In the injectable Phase 1b/2a trial, rates were higher (nausea 82%, vomiting 53%, diarrhea 41%), as is typical for early-phase studies with small group sizes during dose escalation. These rates peaked during the up-titration period and diminished over time.

The American College of Cardiology assessed that both oral and subcutaneous amycretin were "similarly safe and tolerated as GLP-1 monoagonists", meaning the dual mechanism did not introduce new or worse safety signals beyond what is already seen with drugs like semaglutide.

No serious safety signals were identified in any trial. The overall withdrawal rate in the injectable trial was 33%, but 59% of those discontinuations were for reasons unrelated to adverse events (withdrawal of consent, protocol violations).

Two formulations: pill and injection

Amycretin is being developed in two formats simultaneously:

Both formulations are moving to Phase 3. This is significant because no other GLP-1/amylin combination exists as an oral pill. CagriSema is injection-only. Orforglipron (Eli Lilly's oral GLP-1 pill) only targets one pathway. If amycretin's oral formulation holds up in Phase 3, it would be the first oral weight loss drug to hit two appetite pathways at once.

When could amycretin be available?

The timeline is long. Phase 3 obesity trials typically run for 68-76 weeks, and regulatory review adds another 12-18 months. Singapore's HSA usually reviews 12-24 months after FDA approval.

How amycretin compares to other pipeline drugs

These are cross-trial comparisons and should be interpreted cautiously. Different patient populations, trial durations, and dosing protocols make direct comparisons imperfect.

The CagriSema comparison is worth noting. Novo Nordisk's REDEFINE 1 Phase 3 trial for CagriSema showed 22.7% weight loss at 68 weeks, below the company's 25% target. Only about 57% of patients reached the maximum dose. Amycretin's early data suggests it may surpass CagriSema, which is partly why Novo Nordisk is investing heavily in its development as a next-generation candidate.

What this means for patients now

Amycretin is years away from being available to patients. Phase 3 trials are starting in 2026, and even in the best case, approval would not come until around 2030.

In the meantime, the weight loss medications available today are effective. Semaglutide produces approximately 15% weight loss. Tirzepatide produces approximately 20-22%. These are proven, approved treatments with extensive safety data and established dosing protocols.

If you are in Singapore and considering GLP-1 treatment, Trimly prescribes both oral semaglutide (Rybelsus) and injectable options. You do not need to wait for the next generation of drugs to get started.

Frequently asked questions

What is amycretin?

Amycretin is a single engineered molecule developed by Novo Nordisk that activates both GLP-1 and amylin receptors. It is being tested as a once-weekly injection and a once-daily oral pill for weight loss. It entered Phase 3 trials in early 2026.

How much weight loss does amycretin produce?

The injectable version produced 24.3% weight loss at 36 weeks in early trials, with the weight loss curve still declining. The oral version produced 13.1% at 12 weeks. Phase 3 data over longer treatment periods will provide more definitive results.

Is amycretin available in Singapore?

No. Amycretin is in Phase 3 clinical trials and has not been approved anywhere. Based on estimated timelines, it could reach Singapore around 2031-2032 at the earliest.

How is amycretin different from CagriSema?

Both target GLP-1 and amylin receptors, but amycretin is a single fused molecule while CagriSema combines two separate drugs (semaglutide + cagrilintide) in one injection. Amycretin's single-molecule design allows for an oral formulation, which CagriSema cannot offer.

The bottom line

Amycretin's early data is striking: 24.3% weight loss in 36 weeks without plateauing, and an oral formulation that produced 13.1% in 12 weeks. Both the injectable and oral versions are moving to Phase 3.

If these results hold up in larger, longer trials, amycretin could become one of the most effective obesity treatments available, particularly if the oral pill delivers weight loss comparable to what injections offer today. That would remove one of the biggest barriers to treatment for patients who prefer not to inject.

It is early. Phase 1 and 2 data does not always translate to Phase 3 success. But the trajectory is strong, and Novo Nordisk is clearly treating amycretin as a priority.

Amycretin is an investigational drug not approved by any regulatory authority. The clinical trial results discussed are from published peer-reviewed studies but may not reflect final outcomes. Weight loss results vary by individual. This article is for informational purposes only and does not constitute medical advice. Consult your doctor before starting any medication. Trimly is a MOH-licensed telehealth clinic (HCSA License R/25M0505/MDS/001/252).