Amycretin

Amycretin is an experimental drug from Novo Nordisk. Its early weight-loss numbers have turned heads, which is exactly why it keeps popping up on peptide forums and gray-market menus. It is a single molecule (one compound, not a blend) that switches on two receptors at the same time — the GLP-1 receptor and the amylin receptor (both are body signals that affect appetite and blood sugar). It comes in two forms: a once-daily pill and a once-weekly injection. The human studies so far are early and short, and as of mid-2026 amycretin is not approved anywhere in the world. The fair way to describe it: a promising compound with a serious research program behind it, but the work is not finished.

What it is

Amycretin is a long-acting peptide (a short chain of amino acids that acts like a hormone) that Novo Nordisk calls a “first-in-class GLP-1 and amylin receptor agonist” — meaning it is the first drug of its kind that turns on both of those receptors. It packs two appetite and metabolism pathways into one molecule: the appetite and blood-sugar effects of GLP-1, and the fullness and “eat-less” effects of amylin. The peer-reviewed animal research (Kuhre and colleagues) also found it activates a third target, the calcitonin receptor (CTR). That is expected, because the amylin receptor is really the calcitonin receptor paired with helper proteins called RAMP1/2/3. Both the once-daily pill and the once-weekly injection under the skin are in development, and the program is testing it for two uses: overweight/obesity and type 2 diabetes.

The claims

In the official, above-board research, amycretin is being studied for long-term weight management in people who are overweight or obese, and for type 2 diabetes. Online, the pitch is usually built around its biggest weight-loss percentages — especially the high-dose injection figures — and it gets sold as a next-generation upgrade to today’s GLP-1 drugs that you can supposedly get right now. Two things deserve a second look. First, those efficacy figures are early estimates, not the final answer from a large late-stage trial. Second, the “you can buy it now” angle is simply false, because there is no approved product. There is also a popular add-on claim — that amycretin “protects” or preserves lean muscle while you lose fat — and that has not been shown in people (more on this below).

What the evidence actually shows

Two papers were published in The Lancet online on 20 June 2025 and presented at ADA 2025 (abstract 2002-LB).

The first was the oral, first-in-human Phase 1 trial (Gasiorek and colleagues; NCT05369390). “First-in-human” means it was the first time the drug had been tested in people. It was randomized, double-blind and placebo-controlled (participants were sorted by chance, neither they nor the staff knew who got the drug, and some got an inactive dummy) in 144 participants who were overweight or obese and did not have diabetes. There were 364 treatment-emergent adverse events (side effects that showed up during treatment) in 89 of 144 participants (62%), all mild or moderate, mostly stomach- and gut-related (~81%), with no deaths. The trial also reported some early weight-loss signals — the often-quoted numbers are roughly 10.4% at one dose and ~13.1% at the highest dose tested, versus ~1.1% for placebo over 12 weeks, with no sign of leveling off — but these are best read as early exploratory estimates, not the main thing the trial was built to measure.

The second was the injectable Phase 1b/2a trial (Dahl and colleagues; NCT06064006). It was randomized and placebo-controlled in 125 participants (101 on amycretin, 24 on placebo), using a once-weekly injection for up to 36 weeks. Weight loss grew with the dose compared to placebo: −9.7% (1.25 mg, around week 20), −16.2% (5 mg, around week 28), −22.0% (20 mg, week 36) and −24.3% (60 mg, week 36), all statistically significant versus placebo (unlikely to be due to chance). Gut-related side effects were the most common and were mostly mild to moderate.

On the diabetes side, on 25 November 2025 Novo announced positive Phase 2 topline results in type 2 diabetes (448 participants; the once-weekly injection and the once-daily pill versus placebo). The company reported up to roughly 1.8% mean HbA1c reduction (HbA1c is a blood test that reflects average blood sugar over months) with the injection, and ~1.5% with the pill, at 36 weeks. These are company “topline” figures — early headline numbers from the company that have not yet been peer-reviewed (checked by independent experts). And importantly, this was Phase 2 data that clears the way for a planned Phase 3 diabetes program in 2026 — not the start of that late-stage testing.

Two cautions matter most. First, every published study here is small, early-stage and short. They were built mainly to check safety, to track how the drug moves through and acts on the body (its pharmacokinetics and pharmacodynamics), and to find the right dose — so the weight-loss numbers are estimates, not final confirmed results. Second, the muscle-sparing claim is a hope, not a proven human finding. The published human trials did not show a lean-mass benefit, and the animal paper openly said its body-composition method (Echo MRI, a scan that estimates fat and muscle) was not good enough, adding that “further studies using optimised methods, e.g. CT-scan, are needed.” It estimated that roughly 70% of the weight rats lost came from fat and ~30% from lean mass — not a clean muscle-sparing signal.

The animal research (Kuhre and colleagues, eBioMedicine 2025) found about 18% body-weight reduction over 21 days, alongside roughly 47% lower total food intake, in obese rats. In mice, weight loss again grew with the dose, at about 15.8–21.3%. Lab dish tests confirmed the drug switches on the GLP-1, amylin and calcitonin receptors. The authors flagged that the muscle-versus-fat question needs better measurement tools, and that question was left unresolved in the animal work.

Legal and regulatory status

Amycretin is not approved anywhere as of mid-2026 — there is no FDA approval in the US and no EMA approval in Europe. The June 2025 press materials describe it plainly as investigational and “not approved in the US for weight loss.” For obesity, Novo announced on 12 June 2025 that it would push both the injection and the pill straight into Phase 3, based on the early data and feedback from regulators at the end of Phase 2, and planned to start the Phase 3 obesity program in Q1 2026. A companion release on 20 June 2025 went out with the Lancet publication and the ADA presentation. So treat Phase 3 as starting or planned, not done — there are no Phase 3 efficacy results yet. For diabetes, the November 2025 Phase 2 results set up a planned Phase 3 program in 2026. Anything sold today as “amycretin” is unapproved and unregulated, with no guarantee of what it actually is, how pure it is, or how strong the dose is.

For athletes, GLP-1 receptor agonists are not banned. USADA says plainly that “GLP-1s are not prohibited in sport,” while noting that WADA is keeping an eye on their use to decide whether to ban them later. For 2026, GLP-1 receptor agonists are on the WADA Monitoring Program (both in- and out-of-competition) — a watchlist that carries no penalties, not a ban — and no Therapeutic Use Exemption (special permission to use a banned substance) is needed, because they are not on the Prohibited List. Amycretin is not named specifically in the WADA documents available, but as a GLP-1/amylin agonist it falls inside that monitored group based on what we know now. There is a rumor that GLP-1s were moved to a full ban (for example, into category “S4”) in 2026; that could not be confirmed against WADA or USADA primary sources and should not be stated as fact — the official position is still Monitoring Program, not banned. By contrast, IGF-1 (mecasermin) and mechano growth factor (MGF) are banned under WADA category S2 (specifically S2.3, growth factors). Amycretin works in a completely different way — it is not a growth factor — so that ban does not apply to it.

Safety

The side-effect picture from the human trials looks like the GLP-1 and amylin drug families: mostly stomach and gut symptoms such as nausea and vomiting, mostly mild to moderate and generally clearing up, with no deaths in the first-in-human study. Two real warning signs stand out. Side effects became more common at higher doses, and the injection study showed meaningful dropout rates (some for reasons unrelated to side effects) — so how well people tolerate the higher doses is a genuine open question. Long-term safety is simply unknown, because there are no long-term or Phase 3 safety data. It is sensible to keep the broader GLP-1 cautions in mind — gut effects, gallbladder problems, the labeled medullary thyroid cancer/MEN2 warning carried by some GLP-1 drugs, and the concern about food still sitting in the stomach during anesthesia — but none of these have been specifically studied for amycretin. And none of this even covers unregulated gray-market product, which adds its own extra, unmeasured risks. By design, no doses, titration schedules or protocols are given here.

Bottom line

Amycretin is a genuinely interesting compound, backed by a serious, well-funded research program, and it has posted some of the bigger early weight-loss figures reported for an experimental obesity drug. But the published human evidence is early, short and focused on finding the right dose; the diabetes Phase 2 numbers are company topline figures that have not been peer-reviewed yet; Phase 3 has reported nothing; the muscle-sparing story is unproven; and long-term safety is unknown. It is not approved anywhere, and anything sold as amycretin today is unapproved and unregulated. Promising, but unfinished — and not the thing being sold in a vial. Nothing here is medical advice.

Evidence grade: 6/10 · Preliminary.

Sources

• Gasiorek A, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1 trial. The Lancet, 2025. PMID 40550229; NCT05369390.
• Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study. The Lancet, 2025. PMID 40550231; NCT06064006.
• Kuhre RE, et al. The effect of amycretin, a unimolecular GLP-1 and amylin receptor agonist, on body weight and metabolic dysfunction in mice and rats. eBioMedicine, 2025.
• ADA 2025 abstract 2002-LB, Amycretin… Results of a Phase 1b/2a Clinical Trial. Diabetes 74(Suppl_1).
• Novo Nordisk to advance subcutaneous and oral amycretin for weight management into phase 3 clinical development, 12 June 2025.
• Novo Nordisk advances amycretin to Phase 3 (Lancet publication), 20 June 2025.
• USADA, Weight Loss Drugs: What athletes need to know about GLP-1s (Monitoring Program; not prohibited).
• WADA publishes 2026 Prohibited List.
• WADA, The 2026 Monitoring Program (GLP-1 RAs monitored, not prohibited).