Evidence Grade D — Primarily preclinical. 16 published studies, mostly animal models. 1 registered clinical trial.
Medically reviewed by a licensed medical professional
Amycretin is a single molecule from Novo Nordisk that activates both GLP-1 and amylin receptors at once — achieving what CagriSema does with two separate drugs, but from one molecule. An oral tablet formulation has shown strikingly fast weight loss in early trials: 13% in just 12 weeks. The injectable version achieved 24% weight loss at 36 weeks.
Amycretin is also known by these brand and alternate names:
16 published studies: 9 human, 0 animal, 0 in-vitro, 11 reviews
Amycretin is in early-phase development (not yet approved). The oral formulation achieved 13.1% weight loss at just 12 weeks — substantially faster than existing oral options. The subcutaneous formulation achieved 24.3% at 36 weeks. Both results are from Phase I/II trials with relatively small patient numbers.
Amycretin's significance lies in its oral formulation achieving weight loss approaching injectable drugs. If the early results are confirmed in larger trials, an effective oral dual-agonist could significantly expand the obesity treatment population. Phase III trials are anticipated.
Amycretin combines GLP-1 and amylin receptor agonism within a single 68-amino-acid peptide. The molecule uses a calcitonin-based amylin sequence rather than native amylin, which was necessary because native amylin sequences lost potency when fused to GLP-1 analogues. This design achieves the same dual-pathway approach as CagriSema but from a single molecular entity.
Early-phase results are highly promising but based on relatively small patient numbers (125-448 per study). The oral formulation's 13.1% weight loss at 12 weeks is substantially faster than any existing oral option, approaching results typically seen only with injectables. The subcutaneous formulation's 24.3% at 36 weeks is among the highest reported for any obesity compound. Phase III trials for both oral and injectable formulations are planned for early 2026. Key uncertainties include whether the impressive early trajectory will translate proportionally in larger populations and longer treatment durations. Gastrointestinal side effects are consistent with the GLP-1 class. If the oral formulation confirms its early promise, an effective oral dual-agonist pill could significantly expand the obesity treatment population.
PeptideTrace tracks 1 registered clinical trial for Amycretin sourced from ClinicalTrials.gov.
A Research Study of How a New Medicine Called Amycretin, Given as Tablets, Works in Japanese Men With Obesity
Amycretin (INN: zenagamtide; NN 9487) is a unimolecular dual GLP-1 and amylin receptor agonist peptide developed by Novo Nordisk. The 68-amino-acid peptide has a molecular weight of 7,847 Da and molecular formula C343H550N94O116. CAS number: 3005889-81-3. The molecule features an N-terminal GLP-1 agonist moiety connected via a 5-amino-acid linker to a C-terminal calcitonin-based amylin receptor agonist, with C18 diacid acylation enabling albumin binding. Both once-daily oral (using SNAC absorption enhancer) and once-weekly subcutaneous formulations are in development, with Phase 3 initiation planned for Q1 2026.
Amycretin achieves potent dual agonism at both GLP-1R and AMY1-3 receptors from a single molecule. The design employs a calcitonin-based amylin sequence rather than standard amylin sequences, which was necessary because native amylin sequences lost 20-50 fold potency when appended to GLP-1 analogs. This unimolecular approach ensures fixed-ratio receptor engagement regardless of pharmacokinetic variability. Brain access has been confirmed in preclinical models, supporting central appetite suppression through both GLP-1 and amylin pathways simultaneously.
Oral Phase 1 (NCT05369390; N=144; published in Lancet June 2025): the 2x50 mg daily dose achieved -13.1% weight loss at 12 weeks versus -1.2% placebo (P<0.001), substantially exceeding semaglutide's approximately 6% at the same timepoint. Subcutaneous Phase 1b/2a (NCT06064006; N=125; Lancet June 2025): 60 mg weekly achieved -24.3% at 36 weeks versus -1.1% placebo (P<0.0001); the 20 mg dose achieved -22.0%. Phase 2 in T2D (NCT06542874; N=448): subcutaneous formulation produced up to -14.5% weight loss and oral 50 mg up to -10.1%, with HbA1c reductions up to -1.8% (SC) and -1.5% (oral). No weight loss plateau was observed in any trial across all formulations.
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Semaglutide is one of the most extensively studied peptide medications available today, with clinical trial data spanning over 50,000 patients. It is sold as Ozempic for type 2 diabetes (approved 2017), Rybelsus as an oral tablet for diabetes (approved 2019), and Wegovy for weight management (approved 2021). Wegovy has since received additional approvals for reducing heart attack and stroke risk, for use in adolescents aged 12 and older, and for liver disease related to obesity. In clinical trials, patients taking Wegovy lost an average of 14.9% of their body weight over 68 weeks, and the SELECT trial demonstrated a 20% reduction in major cardiovascular events such as heart attack and stroke. Research is now exploring its potential in early Alzheimer's disease. The main side effects are gastrointestinal, particularly nausea, and a key limitation is that most weight tends to return after stopping treatment.
Bimagrumab is in Phase II/III development (not yet approved). A Phase II trial (75 patients with type 2 diabetes and obesity) showed 20.5% fat mass reduction with 3.6% lean mass increase — essentially reshaping body composition without net appetite suppression. The BELIEVE Phase IIb trial (507 patients) showed that bimagrumab plus semaglutide achieved 22% weight loss with the weight lost being 88% fat — significantly better body composition than semaglutide alone. Bimagrumab is not a peptide. Its strategic significance is as a combination partner to address the muscle loss problem inherent in weight loss with current obesity drugs. Eli Lilly's acquisition positions it alongside tirzepatide.
Pemvidutide is in Phase II/III development (not yet approved). In the MOMENTUM Phase II trial (391 patients, 48 weeks), the 2.4 mg dose achieved 15.6% weight loss. Body composition analysis showed 78% of weight lost was fat mass, with only 22% lean mass — a favourable ratio. A Phase IIb MASH trial (212 patients) showed MASH resolution in up to 75% of patients at the highest dose. Pemvidutide's balanced receptor profile and no-titration dosing regimen represent potential practical advantages. The high rate of MASH resolution in Phase II positions it as a candidate for liver disease indications alongside obesity.
Timelines
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
