Amycretin

What is Amycretin?

Amycretin (development code NN9487) is a single-molecule unimolecular dual agonist of the GLP-1 receptor and the amylin receptor. It is developed by Novo Nordisk and is one of the most-watched next-generation obesity peptides — positioned as the successor to both semaglutide (GLP-1) and the CagriSema combination (GLP-1 + amylin).

The unique feature of amycretin is combining both pharmacologies in a single peptide molecule rather than co-administering two peptides. This may simplify manufacturing, dosing, and patient experience.

Amycretin is available in two formulations:

• Subcutaneous once-weekly injection
• Oral daily tablet (using SNAC absorption-enhancement technology, the same as Rybelsus oral semaglutide)

Mechanism of Action

Amycretin combines two complementary anti-obesity pharmacologies in one molecule:

GLP-1 receptor agonism:

• Glucose-dependent insulin secretion
• Glucagon suppression
• Slowed gastric emptying
• Central appetite suppression

Amylin receptor agonism (AMY1, AMY2, AMY3):

• Hindbrain area postrema satiety signaling
• Slowed gastric emptying (complementary to GLP-1)
• Postprandial glucagon suppression
• Modest weight loss

The hypothesis: combining these two non-overlapping satiety pathways in one molecule produces additive or synergistic weight loss compared to either alone, while preserving better lean mass than GLP-1 monotherapy.

Clinical Evidence

Phase 1b/2a subcutaneous amycretin in obesity (Lancet 2025):

• Adults with overweight/obesity, randomized to escalating doses of weekly SC amycretin vs placebo
• Mean weight loss up to 14.5% at week 36
• Significantly greater than expected from semaglutide alone at comparable timepoints

Phase 1 oral amycretin in obesity (Lancet 2025):

• Adults with overweight/obesity, oral daily tablet
• Mean weight loss up to 10.1% at week 36
• Notable as the first oral GLP-1+amylin combination in clinical development

Phase 2 in T2D (November 2025):

• 448 patients with T2D, both SC and oral formulations
• HbA1c reduction up to −1.8% (SC) and −1.5% (oral)
• Body weight reduction up to ~14% (SC), ~10% (oral)
• Tolerability consistent with GLP-1 class

Pipeline Status

Phase 3 obesity program initiating 2026 (sub-cutaneous formulation prioritized first; oral to follow).

The pipeline's strategic logic: Novo Nordisk is positioning amycretin as the next-generation chronic weight management peptide to follow CagriSema (which is currently under FDA NDA review). Where CagriSema is two co-administered peptides, amycretin combines both pharmacologies in one molecule — simplifying the dosing and potentially improving manufacturing economics.

Place in Future Therapy

If approved (likely 2028-2029 timing), amycretin would compete in:

• Obesity — vs semaglutide, tirzepatide, CagriSema, retatrutide, MariTide
• T2D — vs semaglutide, tirzepatide, mazdutide

Its key differentiator is single-molecule simplicity with dual mechanism, plus the unique availability of both injectable and oral formulations from a single drug entity.

Safety Profile

Phase 2 adverse events are consistent with the GLP-1 class:

• Nausea, vomiting, diarrhea (predominantly during dose titration)
• Decreased appetite (intended)
• Manageable with slow titration

The amylin component does not appear to add meaningful adverse events beyond the GLP-1 background; it primarily contributes to efficacy.

Distinction from CagriSema and Cagrilintide

Amycretin is the conceptual successor to CagriSema — taking the same dual-mechanism approach but in one molecule rather than two.