Amycretin (Zenagamtide, NN9487), Novo Nordisk single-molecule GLP-1/amylin co-agonist

Amycretin (also written as Zenagamtide in INN-style documentation) is a single-molecule peptide engineered by Novo Nordisk to activate two distinct receptor systems simultaneously:

• GLP-1 receptor, the same target as semaglutide, liraglutide, and the broader GLP-1 class; produces appetite suppression, slowed gastric emptying, glucose-dependent insulin release, and the well-characterized weight-loss effects.
• Amylin receptor, the same target as cagrilintide and pramlintide; produces central appetite suppression through brainstem area postrema and nucleus tractus solitarius, slowed gastric emptying via vagal inhibition, post-prandial glucagon suppression, and reduced food-reward signaling.

The strategic comparison point is CagriSema, Novo Nordisk's two-compound combination of semaglutide + cagrilintide that delivered ~22.7% mean weight loss at 68 weeks in REDEFINE Phase 3. Amycretin captures the same GLP-1 + amylin co-agonist mechanism but in a single engineered molecule rather than two co-formulated compounds. If Phase 3 efficacy matches or exceeds CagriSema's, the manufacturing simplicity and dosing flexibility of a single-molecule approach may give amycretin a meaningful competitive advantage.

Amycretin emerged from Novo Nordisk's research into single-molecule incretin co-agonists, the strategic alternative to the two-compound combination approach that produced CagriSema (semaglutide + cagrilintide as separate compounds in one injection). The hypothesis: combine GLP-1 and amylin agonism within a single engineered peptide rather than co-formulating two distinct compounds. The single-molecule approach has several theoretical advantages, simpler manufacturing, better pharmacokinetic consistency, no risk of differential degradation of the two components, and potential for oral formulation development that's difficult with two-compound mixtures.

The development name through 2024-2025 was Amycretin; the proposed International Nonproprietary Name (INN) is Zenagamtide, which appeared in 2025 regulatory documents as Novo Nordisk advanced the compound through development.

First human data appeared in 2024-2025. The Lancet published Phase 1b/2a results in 2025 (Jensen et al.) characterizing safety, pharmacokinetics, and initial efficacy across both subcutaneous and oral formulations. The Phase 2 trial in adults with type 2 diabetes was reported in late 2025 (Healio coverage November 2025), showing meaningful HbA1c reductions and weight loss across dose ranges. Novo Nordisk announced Phase 3 program advancement for 2026 obesity development.

The dual-receptor mechanism captures the same biology as CagriSema but through a different molecular vehicle:

• GLP-1 axis, central appetite suppression via hypothalamic and brainstem receptors, slowed gastric emptying via vagal mechanisms, glucose-dependent insulin release from pancreatic beta cells, glucagon suppression from alpha cells, and possibly direct effects on reward circuits.
• Amylin axis, brainstem area postrema and nucleus tractus solitarius activation produces a distinct satiety signal; slowed gastric emptying via different vagal pathways; post-prandial glucagon suppression; reduced palatability-driven overconsumption.
• Mechanistic non-overlap, the two axes converge at energy homeostasis but use different receptor families and different neural circuits. Blocking one doesn't abolish the other. The pharmacological rationale for combining them is that the effects are additive rather than redundant.

The single-molecule approach has a specific pharmacological advantage: the two receptor activities are guaranteed to be present in the same molar ratio at every receptor in every tissue, which two-compound combinations can't perfectly match (the two compounds may have slightly different tissue distributions, half-lives, or degradation patterns). Whether this matters clinically is one of the open questions Phase 3 will help answer.

The subcutaneous formulation supports once-weekly dosing with steady-state achieved over multiple weeks of administration. The oral formulation development is structurally interesting, Novo Nordisk's existing oral semaglutide (Rybelsus) demonstrated the feasibility of oral GLP-1 administration via the SNAC absorption enhancer; amycretin's oral formulation extends that approach to a co-agonist.

Plasma half-life supports the once-weekly dosing schedule. Both formulations target the same mechanism (GLP-1 + amylin co-agonism); the choice between routes is primarily about patient preference, oral bioavailability constraints (much lower for oral peptides), and dose magnitude considerations.

The peer-reviewed literature on Amycretin is summarized below across two tiers: human research (the highest standard), and preclinical / emerging research (animal models and early-stage human work).

This table summarizes commonly discussed claims and how the published evidence weighs in. The aim is clarity, supported claims, claims that look promising but need more data, and claims that outrun the science.

Subcutaneous formulation in Phase 3 trials uses once-weekly injection with standard incretin-class titration patterns. The oral formulation under development uses standard incretin-class daily dosing patterns with absorption-enhancer-supported formulation (similar in concept to the SNAC excipient used in Rybelsus oral semaglutide).

Amycretin is investigational and not commercially available. Access is limited to clinical trial enrollment. The compound is not appropriate for off-label use, research-peptide-vendor sourcing, or community administration.

Amycretin (proposed INN: Zenagamtide) is one of the most strategically interesting molecules in the modern GLP-1 class, Novo Nordisk's single-molecule alternative to CagriSema's two-compound combination. The single-molecule architecture provides manufacturing simplicity, pharmacokinetic consistency, and oral formulation development potential that two-compound mixtures struggle to deliver. If Phase 3 confirms the Phase 2 efficacy at scale, amycretin could become a competitive alternative to both CagriSema and tirzepatide in the GLP-1 + amylin or GLP-1 + GIP dual-receptor space.

For users tracking the broader incretin pipeline through 2027-2028, amycretin sits alongside Retatrutide (triple agonist, deeper weight loss), MariTide (monthly dosing, GIP antagonism), and the established Tirzepatide (dual GIP/GLP-1, currently approved). Each represents a different strategic bet on which receptor combination and dosing format will define the next decade of obesity pharmacology.

For the broader context, see our existing Amycretin explainer article for the strategic positioning, our CagriSema page for the two-compound comparator, and our Best Peptides for Weight Loss 2026 ranking for the overall class comparison.