History

Amycretin is developed by Novo Nordisk as a single-molecule agonist of both the GLP-1 and amylin receptors, with oral (once-daily) and subcutaneous (once-weekly) forms. Two human trials were published in The Lancet online on 20 June 2025 and presented at ADA 2025: a first-in-human oral Phase 1 (NCT05369390) and a subcutaneous Phase 1b/2a (NCT06064006). On 12 June 2025 Novo announced it would advance both forms straight to Phase 3 for weight management, planning to initiate the obesity program in Q1 2026. On 25 November 2025 Novo reported positive Phase 2 topline results in type 2 diabetes, setting up a Phase 3 diabetes program in 2026.

Amycretin is an investigational drug from Novo Nordisk that has generated some striking early-phase weight-loss numbers, which is exactly why it shows up on peptide forums and gray-market menus. It is a single-molecule (“unimolecular”) peptide that activates two receptors at once — the GLP-1 receptor and the amylin receptor — in both an oral once-daily and an injectable once-weekly form. The human data published so far are early-phase and short, and as of mid-2026 amycretin is not approved anywhere in the world. The honest framing is a promising compound with a serious development program, still unfinished.

What it is

Amycretin is a long-acting peptide that Novo Nordisk positions as a “first-in-class GLP-1 and amylin receptor agonist.” It combines two distinct appetite and metabolic pathways in a single molecule: the incretin-driven appetite and glycemic effects of GLP-1, and the satiety and reduced-energy-intake effects mediated by amylin. According to the peer-reviewed preclinical pharmacology (Kuhre and colleagues), it also activates the calcitonin receptor (CTR) — which is expected, because the amylin receptor is the calcitonin receptor in complex with RAMP1/2/3 accessory proteins. Both an oral (once-daily) and an injectable (subcutaneous, once-weekly) form are in development, and the program covers both overweight/obesity and type 2 diabetes.

The claims

In legitimate clinical development, amycretin is being investigated for chronic weight management in overweight/obesity and for type 2 diabetes. Online, it tends to be promoted on the strength of its headline weight-loss percentages — particularly the high-dose subcutaneous figures — and framed as a next-generation successor to existing GLP-1 drugs that you can obtain now. Two things deserve scrutiny: the efficacy figures are early-phase estimates, not confirmatory Phase 3 outcomes, and the availability framing is false, because there is no approved product. A common add-on claim — that amycretin “spares” or preserves lean muscle mass — is not an established human finding (see 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 oral, first-in-human Phase 1 trial (Gasiorek and colleagues; NCT05369390) was randomized, double-blind and placebo-controlled in 144 participants with overweight/obesity and no diabetes. There were 364 treatment-emergent adverse events in 89 of 144 participants (62%), all mild or moderate, predominantly gastrointestinal (~81%), with no deaths. Exploratory weight-loss signals were reported — the widely cited headline figures are roughly 10.4% at one dose level and ~13.1% at the highest dose tested, versus ~1.1% for placebo over 12 weeks, with no plateau — but these are best read as early-phase exploratory estimates, not the trial’s primary endpoint.

The subcutaneous Phase 1b/2a trial (Dahl and colleagues; NCT06064006) was randomized and placebo-controlled in 125 participants (101 amycretin, 24 placebo), with once-weekly injection for up to 36 weeks. It showed dose-dependent weight loss versus placebo: −9.7% (1.25 mg, ~week 20), −16.2% (5 mg, ~week 28), −22.0% (20 mg, week 36) and −24.3% (60 mg, week 36), all statistically significant versus placebo. GI adverse events were most common and mostly mild to moderate.

For diabetes, on 25 November 2025 Novo announced positive Phase 2 topline results in type 2 diabetes (448 participants; once-weekly SC and once-daily oral versus placebo), reporting up to roughly 1.8% mean HbA1c reduction with the SC form and ~1.5% with the oral form at 36 weeks. These are company topline figures and are not yet peer-reviewed; importantly, this was Phase 2 data enabling a planned Phase 3 diabetes program in 2026, not entry into late-stage testing.

Two caveats matter most. First, all the published studies are small, early-phase and short, designed primarily for safety, pharmacokinetics/pharmacodynamics and dose-finding — the weight-loss numbers are estimates, not confirmatory results. Second, the muscle/lean-mass-sparing claim is a hypothesis, not an established human finding: the published human trials did not demonstrate a lean-mass benefit, and the preclinical paper explicitly said its body-composition methods (Echo MRI) were insufficient and that “further studies using optimised methods, e.g. CT-scan, are needed,” estimating roughly 70% of rat weight loss from fat and ~30% from lean mass — not a clean sparing signal.

The preclinical work (Kuhre and colleagues, eBioMedicine 2025) found roughly 18% body-weight reduction over 21 days with about 47% lower total energy intake in diet-induced obese rats, dose-dependent ~15.8–21.3% weight loss in mice, and confirmed in-vitro agonism at the GLP-1, amylin and calcitonin receptors. The authors flagged that lean-mass effects need better methods, and that question was not resolved preclinically.

Legal and regulatory status

Amycretin is not approved anywhere as of mid-2026 — no FDA or EMA marketing authorization. The June 2025 press materials describe it explicitly as investigational and “not approved in the US for weight loss.” For obesity, Novo announced on 12 June 2025 that it would advance both the subcutaneous and oral forms straight to Phase 3 based on early-phase data and end-of-phase-2 regulatory feedback, planning to initiate the Phase 3 obesity program in Q1 2026; a paired 20 June 2025 release accompanied the Lancet publication and ADA presentation. Treat Phase 3 as initiated/planned, not completed — no Phase 3 efficacy outcomes exist yet. For diabetes, the November 2025 Phase 2 results set up a planned Phase 3 program in 2026. Any product sold today as “amycretin” is unapproved and unregulated, with no assurance of identity, purity or dose.

For athletes, GLP-1 receptor agonists are not prohibited. USADA states plainly that “GLP-1s are not prohibited in sport,” while noting that WADA is monitoring their use to decide whether they should be prohibited in the future. For 2026, GLP-1 receptor agonists are on the WADA Monitoring Program (both in- and out-of-competition) — a watchlist that imposes no sanctions, not a ban — and no Therapeutic Use Exemption is required because they are not on the Prohibited List. Amycretin is not specifically named on the WADA documents available; as a GLP-1/amylin agonist it falls within that monitored category on current information. A rumor that GLP-1s were moved to full prohibition (for example, to category “S4”) in 2026 could not be corroborated against WADA or USADA primary sources and should not be stated as fact — the authoritative position remains Monitoring Program, not banned. For contrast, IGF-1 (mecasermin) and mechano growth factor (MGF) are prohibited under WADA category S2 (specifically S2.3, growth factors); amycretin is mechanistically unrelated, as it is not a growth factor, so that prohibition does not apply.

Safety

The human-trial safety profile is consistent with the GLP-1 and amylin classes: predominantly gastrointestinal adverse events such as nausea and vomiting, mostly mild to moderate and generally resolving, with no deaths in the first-in-human study. Two real signals deserve attention: adverse-event frequency was dose-dependent, and the subcutaneous study showed meaningful discontinuation rates (some unrelated to adverse events), so high-dose tolerability is a genuine open question. Long-term safety is simply unknown — there are no long-term or Phase 3 safety data. Class-level GLP-1 cautions (gastrointestinal effects, gallbladder events, the labeled medullary thyroid carcinoma/MEN2 concern for some GLP-1 agonists, and anesthesia/retained-gastric-content considerations) are reasonable to keep in mind, but they have not been specifically characterized for amycretin. None of this applies to unregulated gray-market product, which carries additional and unquantified risks. No doses, titration schedules or protocols are provided here by design.

Bottom line

Amycretin is a genuinely interesting compound with a serious, well-funded development program and some of the larger early-phase weight-loss figures reported for an investigational obesity drug. But the published human evidence is early-phase, short and dose-finding; the diabetes Phase 2 data are company topline and not yet peer-reviewed; Phase 3 has not reported anything; the lean-mass-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: Preliminary human.