Inside the body with Amycretin

A C18 diacid side chain on Lys37 (GLP-1 7-37 numbering) enables reversible albumin binding and a long systemic half-life; an Aib substitution in the N-terminal GLP-1 region stabilises against DPP-4. In a single-dose study in 42 adults, the geometric mean terminal half-life was 88.1 h with normal kidney function and 94.0 to 112.8 h across mild to end-stage kidney impairment, with median time to peak concentration of 36 to 48 h. Animal data: preclinical terminal half-lives (harmonic means) rose with species size: 3.65 h in mice (subcutaneous), 29.7 h in monkeys (subcutaneous) and 54.1 h in minipigs (intravenous).[src][src]

Animal-only: after a single dose of a fluorescently labelled version (amycretin-VT750) in mice, signal was seen in the circumventricular organs (area postrema, median eminence, vascular organ of the lamina terminalis, subfornical organ) and in blood-brain-barrier-protected regions including the arcuate nucleus, nucleus of the solitary tract and dorsal motor nucleus of the vagus. Semaglutide-VT750 was detected in the same regions. Amylin receptors sit in the hypothalamus and dorsal vagal complex of the hindbrain (review). Direct human brain-distribution data for amycretin were not found.[src][src]

In cell-based assays amycretin activated human, mouse and rat GLP-1, amylin and calcitonin receptors. Animal-only: in diet-induced obese rats, 21 days of treatment reduced total energy intake by 47% and body weight by 18% while energy expenditure was maintained. Human data: in the phase 1b/2a study, body-weight change was -24.3% versus -1.1% with placebo at week 36 at the highest dose tested, with high discontinuation. A 2026 review describes engagement of hindbrain-mediated satiety pathways and delayed gastric emptying as the proposed mechanisms, but appetite and food-intake measures in people are not reported in the primary papers reviewed here.[src][src][src]

Delayed gastric emptying is a recognised action of amylin and of GLP-1 receptor agonists as a class, and a 2026 review attributes it to amycretin. Novo Nordisk ran a phase 1 study (NCT06461039, completed 2025) whose primary aim was an interaction with an oral contraceptive and which also measured gastric emptying (paracetamol absorption after a standard meal); no results are posted on ClinicalTrials.gov and no publication was found, so an amycretin-specific human effect size is not stated.[src][src][src]

GLP-1 receptor agonism stimulates insulin secretion and lowers glucagon in a glucose-dependent manner (label of the reference GLP-1 receptor agonist semaglutide); amylin suppresses glucagon secretion (review). These pancreatic actions are class-level mechanisms and were not isolated for amycretin in the sources reviewed. The clinical effect is measured in the phase 2 diabetes trials.[src][src][src]

Animal-only: in diet-induced obese rats treated for 35 days, a hyperinsulinaemic-euglycaemic clamp showed higher glucose infusion rates than vehicle, and amycretin improved histological hallmarks of MASLD, primarily by reducing steatosis. No human liver-outcome data for amycretin were found.[src]

In a 36-week, placebo-controlled phase 2 trial (NCT06542874; subcutaneous and oral parts reported separately) in adults with type 2 diabetes on metformin (baseline HbA1c about 7.8 to 8.1%), subcutaneous zenagamtide lowered HbA1c by 0.9% at the lowest dose up to 1.7% at the highest dose (estimated treatment difference versus placebo -0.77 to -1.56 percentage points); oral zenagamtide lowered HbA1c by 0.9% to 1.4% (ETD -0.5 to -1.09). Company topline figures reported body-weight loss of up to 14.5% (subcutaneous, versus 2.6% with placebo) and 10.1% (oral, versus 2.5% with placebo).[src][src][src]