Amycretin

What Is Amycretin?

Amycretin is an investigational peptide that activates two hormone receptor systems with a single molecule: the GLP-1 receptor and the amylin receptor.^[1] The first-in-human trial report describes it as a first-in-class GLP-1 and amylin receptor agonist.^[1]

Its design combines two pathways that have each produced weight loss and glucose lowering in people with overweight, obesity and type 2 diabetes.^[1] GLP-1 receptor agonists such as semaglutide act on the incretin pathway, while amylin receptor agonists, such as the earlier analog pramlintide, act centrally to induce satiety and suppress mealtime glucagon release.^[2]

Amycretin differs from the cagrilintide–semaglutide combination in being one molecule rather than two co-formulated peptides. Reviews describe it as a unimolecular amylin receptor, calcitonin receptor and GLP-1 receptor multi-agonist that has been developed in both injectable and tablet forms.^[2] The same review explains that newer amylin analogs were designed using a better understanding of the heterodimeric amylin–calcitonin receptor complexes and of amylin structure-function relationships.^[2]

Chemical Structure and Molecular Identity

Amycretin is a synthetic peptide engineered to act at GLP-1, amylin and calcitonin receptors, but its full structure is not available in the sources used for this page.^[2][3] As of October 2026, PubChem did not return a compound record for amycretin, so this page does not state a molecular formula, molecular weight or CAS Registry Number.

What the literature establishes

• Single molecule: it is described as a unimolecular or single-molecule agonist, not a mixture of two peptides.^[1][4]
• Receptor coverage: in cell-based systems it activated human, mouse and rat GLP-1, amylin and calcitonin receptors.^[3]
• Formulations studied: trials have tested an oral form and a subcutaneous form.^[1][4]
• Development code: NN9487.

Because the sequence and any chemical modifications are not reported in the cited abstracts, no amino-acid sequence is given here. A 2025 review places amycretin among a wave of multi-targeting synthetic incretin peptides that also includes dual GLP-1/glucagon and triple GLP-1/GIP/glucagon receptor agonists.^[5]

Research History and Development

Amycretin’s peer-reviewed record dates mainly from 2025, when a preclinical study in rodents and two early-phase human trials, one oral and one subcutaneous, were published.

Preclinical work

A 2025 study characterized receptor activation in cell-based systems and tested amycretin in mice and rats. It measured body weight and composition, energy intake and expenditure, insulin sensitivity, fatty liver disease and brain access.^[3]

First-in-human oral trial

A phase 1, randomized, double-blind, placebo-controlled multipart trial tested an oral form at a single clinical research unit in San Antonio, Texas.^[1] It enrolled adults aged 18 to 55 years with a BMI of 25.0 to 34.9 kg/m² in the single- and multiple-ascending-dose parts and 27.0 to 39.9 kg/m² in a later dose-escalation part, which randomized 60 participants.^[1] The single-dose part used six ascending-dose groups with a 21-day follow-up, and the multiple-dose part used a 10-day intervention period followed by 21 days of follow-up.^[1]

Subcutaneous phase 1b/2a trial

A randomized, placebo-controlled phase 1b/2a study at the same San Antonio site tested a subcutaneous form in adults aged 18 to 55 with a BMI of 27.0 to 39.9 kg/m² (NCT06064006).^[4] It had five parts: a single-ascending-dose part, a multiple-ascending-dose escalation part lasting 36 weeks, and three dose-response parts lasting 36, 28 and 20 weeks.^[4] The primary endpoint was the number of treatment-emergent adverse events; secondary endpoints included pharmacokinetic exposure and relative change in body weight.^[4]

Mechanisms Studied in Research

Amycretin is studied as a molecule that reduces food intake through combined GLP-1 and amylin receptor signaling, with reviewers pointing to hindbrain satiety pathways and delayed gastric emptying.^[6]

Receptor activation

In cell-based systems, amycretin activated human, mouse and rat GLP-1 receptors, amylin receptors and calcitonin receptors.^[3] This cross-species activity is relevant because the preclinical efficacy work was carried out in mice and rats.^[3] A 2025 review classifies amycretin as a unimolecular GLP-1/amylin receptor dual agonist, one of several multi-targeting incretin-based peptides in development.^[5]

Brain targeting

In mice, amycretin reached key brain areas that regulate food intake.^[3] A 2026 review proposes that the dual-agonist mechanism engages hindbrain-mediated satiety pathways and delays gastric emptying, which the authors suggest may help overcome weight-loss plateaus.^[6]

Energy balance and insulin sensitivity

In diet-induced obese rats, amycretin lowered energy intake while energy expenditure was maintained.^[3] Insulin sensitivity improved compared with vehicle controls, shown by higher glucose infusion rates during a hyperinsulinemic euglycemic clamp.^[3] A 2026 endocrine review groups amylin-based agents, including amycretin, as enhancing satiety and glycemic outcomes through actions complementary to GLP-1 receptor agonism.^[7] The same review describes next-generation agents that engage GLP-1 receptors together with receptors for GIP, glucagon, amylin or peptide YY.^[7]

Key Findings From Published Studies

Published data show substantial weight reduction with amycretin in rodents and in early human trials, with a safety profile that reviewers describe as consistent with incretin-based drugs.^[3][6]

Animal models

In diet-induced obese rats treated for 21 days, total energy intake fell by 47% and body weight by 18% compared with vehicle, while energy expenditure was maintained.^[3] Amycretin also improved histological hallmarks of metabolic dysfunction-associated steatotic liver disease (MASLD), mainly by reducing steatosis, and improved MASLD activity scores.^[3] The authors concluded that, in mice and rats, amycretin reduced body weight, enhanced insulin sensitivity and improved liver disease scores.^[3]

Human trials

A 2026 review summarizing the clinical program reports weight reductions of up to 13.1% with oral administration over 12 weeks and up to 24.3% with subcutaneous delivery over 36 weeks.^[6] The same review describes the safety profile as consistent with incretin-based drug classes.^[6] The primary trial reports focused on safety, tolerability and pharmacokinetics, with body-weight change as a secondary or pharmacodynamic endpoint.^[1][4]

Research directions

Reviewers have proposed studying amycretin together with insulin-independent agents such as SGLT2 inhibitors to examine cardio-renal outcomes.^[6] These proposals are hypotheses, not trial results.

Because amycretin has no public PubChem structure record, batch-specific HPLC and mass spectrometry certificates of analysis are the main way to verify identity.

Regulatory and Research Status

Amycretin is an investigational compound and is not approved by the US Food and Drug Administration (FDA). The published human data come from phase 1 and phase 1b/2a trials.^[1][4]

Reviews of next-generation obesity and diabetes therapies list amycretin among the emerging multi-receptor peptides, alongside glucagon co-agonists such as survodutide and mazdutide and the triple agonist retatrutide.^[7][5] A review of long-acting amylin-related peptides notes that gastrointestinal side effects, especially nausea, are common during initiation and up-titration of amylin analogs but mostly resolve with continued use.^[2]

Both published human trials were early-phase studies at a single research site, and results from larger, longer controlled trials are not part of the cited literature. Outside registered clinical trials, amycretin is not approved for human use, and material described as amycretin is intended for laboratory research only.