Evidence Grade D — Primarily preclinical. 15 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:
15 published studies: 9 human, 0 animal, 0 in-vitro, 10 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.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Danuglipron's original twice-daily formulation achieved 8–13% weight loss in Phase IIb but with treatment discontinuation rates exceeding 50%, with nausea affecting up to 73% of patients. Pfizer discontinued the twice-daily formulation and is developing a once-daily modified-release version. Danuglipron is not a peptide. Its development trajectory illustrates that even effective weight loss compounds can fail commercially if tolerability is inadequate. The reformulation effort aims to reduce peak drug concentrations that likely drive the gastrointestinal side effects.
Setmelanotide is marketed as Imcivree (Rhythm Pharmaceuticals; approved November 2020 for POMC, PCSK1, or LEPR deficiency; June 2022 for Bardet-Biedl syndrome; December 2024 expanded to patients aged 2 years and older). Genetic testing confirming an eligible mutation is required before treatment. In patients with POMC or PCSK1 deficiency, approximately 80% achieved at least 10% weight loss in clinical trials. In Bardet-Biedl syndrome, 32.3% achieved the same threshold. The most common side effects are injection-site reactions and skin darkening (due to the melanocortin pathway's connection to pigmentation). Setmelanotide exemplifies precision medicine — it is highly effective in the specific genetic populations it targets but is not indicated for common obesity.
CT-388 is in Phase II/III development (not yet approved). Phase II results (469 patients, 48 weeks) showed 22.5% placebo-adjusted weight loss at the highest dose, with low discontinuation rates due to adverse events (5.9%). Phase III trials are underway. The combination of high efficacy and low discontinuation rates in Phase II is notable — many obesity drugs achieve high weight loss but suffer from tolerability-driven dropouts. Roche's $2.7 billion acquisition of the developer signals significant confidence in the programme.
Timelines
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