Amycretin

Amycretin is Novo Nordisk’s investigational, single-molecule GLP-1 and amylin agonist for weight management. Early randomized human trials found substantial weight loss with weekly injections and daily tablets, including a model-estimated 24.3% at 36 weeks at the highest injected dose. Amycretin entered Phase 3 in 2026 but is not FDA-approved, and gastrointestinal events were frequent.

Key facts

• Evidence: Human RCT, helped; still early-phase for the published weight-loss results
• U.S. status: Investigational as of July 2026; no approved indication
• Studied forms: Once-weekly subcutaneous injection and once-daily oral tablet
• Main risk signal: Frequent nausea, vomiting, and diarrhea, especially at higher doses
• Sport: No simple clearance; USADA says athletes using experimental trial drugs should ask its Drug Reference Line whether a prohibited class applies

What is amycretin?

Amycretin is a synthetic peptide that makes the CagriSema idea into one molecule: activate both GLP-1 and amylin signaling, rather than combining two separate drugs. Novo Nordisk renamed the candidate zenagamtide in 2026; NNC0487-0111 and NN9487 are development codes for the same program. The name changed. The molecule did not.

The GLP-1 and metabolic peptide hub places that design beside approved GLP-1 drugs and other multi-receptor candidates. Unlike CagriSema, which pairs semaglutide with cagrilintide, amycretin joins GLP-1-like and amylin-like activity in a single engineered peptide.

How does amycretin work?

Amycretin activates GLP-1, amylin, and calcitonin receptors, stacking two biological “meal finished” messages in one molecule. GLP-1 signaling lowers appetite and supports insulin release when glucose is high. Amylin signaling adds satiety and can slow stomach emptying. Think of one key cut to open two related locks, rather than two keys on the same ring.

The oral formulation adds SNAC, an absorption helper also used with oral semaglutide. The peptide also carries a fatty-acid side chain that promotes reversible albumin binding, helping it remain in circulation. Those design choices allow once-daily amycretin oral tablets and once-weekly injections to come from the same drug program.

What do the amycretin results actually show?

Amycretin results show a strong early human weight-loss signal, with an equally important asterisk: the published studies were small, single-center, dose-finding trials. In the subcutaneous Phase 1b/2a study, 125 adults were randomized across several parts. The trial was designed mainly to study safety, tolerability, and dose behavior—not to deliver a Phase 3-sized effectiveness verdict.

At week 36, the model-estimated mean amycretin weight loss was 24.3% with 60 mg versus 1.1% with placebo, and 22.0% with 20 mg versus a 1.9% gain with placebo (Dahl et al., PMID 40550231). Lower-dose groups lost 16.2% at 28 weeks with 5 mg and 9.7% at 20 weeks with 1.25 mg.

The 24.3% headline came from a dose-escalation part containing only 22 people; 17 received amycretin, and 10 of those 17 withdrew. Across the whole study, 33% withdrew, though the paper says 59% of discontinuations were for reasons unrelated to treatment-emergent adverse events. That context rarely survives the headline.

Does oral amycretin work too?

Amycretin oral tablets also reduced weight in a randomized first-in-human trial, but only over 12 weeks. Among 144 enrolled adults, the longer multiple-dose groups produced mean losses from 10.4% with 50 mg daily to 13.1% with two 50 mg tablets daily, versus 1.2% with placebo (Gasiorek et al., PMID 40550229).

The amycretin oral result is not proof that a pill will match the weekly injection over a full obesity trial. Different treatment lengths, dose schedules, and participant groups make a casual cross-trial race unreliable. Phase 3 is where durability, discontinuation, and a fairer benefit-risk picture should become clearer.

Is amycretin safe? What are the side effects?

Amycretin’s clearest safety problem so far is gastrointestinal intolerance: nausea, vomiting, and diarrhea occurred often, rose with dose, and were joined by decreased appetite. Most events in the published trials were mild or moderate and resolved by study end. “Mostly mild” is useful context; “frequent” belongs in the same sentence.

In the oral trial, 89 of 144 participants reported a treatment-emergent adverse event. Gastrointestinal problems affected 72 of those 89 people and accounted for 180 of 364 recorded events. The injection trial likewise reported a high GI-event frequency and numerous withdrawals. Long-term safety, rare harms, gallbladder outcomes, and effects after treatment stops remain less settled than the scale numbers.

What amycretin dosage did the studies use?

Amycretin dosage varied widely because these were dose-finding experiments, not prescribing instructions. The injection study escalated once-weekly doses from 0.3 mg to maintenance doses of 1.25, 5, 20, or 60 mg, depending on the trial part. The oral study tested daily regimens up to 100 mg as two 50 mg tablets.

Those amounts describe what researchers tested. There is no FDA-approved amycretin dosage, retail pen, tablet, or reconstitution protocol. The high injected doses also used gradual escalation, so copying the final number while skipping the study design would copy the least useful part of the paper.

Amycretin vs CagriSema: what is the difference?

Amycretin vs CagriSema is one dual-action molecule versus a fixed combination of two molecules. Amycretin carries GLP-1 and amylin activity within one engineered peptide. CagriSema combines cagrilintide, a long-acting amylin analogue, with semaglutide. Both aim at the same broad pair of appetite pathways.

No published head-to-head trial has compared them. CagriSema has large Phase 3 obesity data; amycretin’s published weight-loss evidence remains Phase 1b/2a. Comparing CagriSema’s 68-week average with amycretin’s small 36-week dose cohorts as if they shared one starting gun would be clean arithmetic and poor science.

Is amycretin FDA-approved in 2026?

Amycretin is not FDA-approved in the United States as of July 2026. Novo Nordisk moved subcutaneous zenagamtide into the Phase 3 AMAZE program in 2026, with registered studies in obesity, type 2 diabetes, weight maintenance, sleep apnea, knee osteoarthritis, and heart failure. Phase 3 means serious development, not permission to prescribe.

The practical distinction is blunt: amycretin weight loss is supported by randomized human evidence, but no approved product or label exists yet. FDA’s 2026 novel-approval list does not include amycretin or zenagamtide, while ClinicalTrials.gov lists active Phase 3 research. The next useful evidence will come from those larger trials, especially their dropout rates and longer safety follow-up.