Amycretin

Amycretin is an investigational peptide from Novo Nordisk that combines GLP-1 and amylin receptor agonism into a single, unimolecular peptide — as opposed to co-formulating two separate drugs, the way cagrilintide (an amylin analogue) is combined with semaglutide in CagriSema. Amylin receptor agonism is thought to activate hypothalamic POMC neurons and suppress orexigenic NPY/AgRP signaling, complementing GLP-1's own appetite and gastric-emptying effects.

Both subcutaneous (injectable) and oral (tablet) formulations are in parallel development. As of mid-2026, Novo Nordisk has described amycretin as advancing toward Phase 3 based on early-phase results, though public confirmation that Phase 3 dosing has actually begun (versus still being initiated) was not found in sources reviewed for this entry.

Early trial data has been strong: a Phase 1b/2a subcutaneous trial reported up to 22% weight loss after 36 weeks at the highest dose, and a mid-stage 448-patient trial spanning subcutaneous and oral arms reported up to 14.5% weight loss at 36 weeks. An oral, 12-week exploratory dataset reported 13.1% mean weight loss at the 100 mg/day dose.

// UNIMOLECULAR GLP-1/AMYLIN DUAL AGONISM

Amycretin is engineered as a single peptide with agonist activity at both the GLP-1 receptor and the amylin receptor, rather than requiring two separately dosed drugs. This distinguishes it from the cagrilintide + semaglutide (CagriSema) approach, which pairs two distinct peptides in one injection.

// COMPLEMENTARY APPETITE PATHWAYS

Amylin receptor agonism is proposed to activate POMC neurons and suppress NPY/AgRP orexigenic signaling in the hypothalamus, working alongside GLP-1's own satiety and gastric-emptying effects via brainstem (nucleus tractus solitarius) circuitry. The more granular pharmacological distinction between amylin-pathway synergy and GIP-pathway synergy (as in tirzepatide-style drugs) — for example on nausea, glucose counter-regulation, or lean-mass preservation — was not detailed in a primary source reviewed for this entry and is left unstated rather than inferred.

Phase 1b/2a (subcutaneous, weekly injections): up to 22% weight loss after 36 weeks at the highest dose tested.

Mid-stage trial (448 patients, subcutaneous and oral arms combined): up to 14.5% weight loss at 36 weeks.

Oral, 12-week exploratory data: 13.1% mean weight loss at the 100 mg/day dose vs. 1.2% placebo.

Safety: gastrointestinal adverse events dominate and are dose-dependent — at higher subcutaneous doses, GI adverse events occurred in roughly 87.5% of subjects (nausea ~75%, vomiting ~56.3%), described as mostly mild-to-moderate and consistent with the broader GLP-1/amylin drug class. Phase 3 trial names, timelines, and safety data were not found in sources reviewed and are therefore not stated here.