Zenagamtide

Overview

Zenagamtide (Novo Nordisk codes NNC0487-0111 / NN9487; formerly amycretin) is an investigational unimolecular agonist described in 2026 Lancet phase 2 type 2 diabetes papers as acting at GLP-1, amylin, and calcitonin receptors. Development includes oral (once daily) and subcutaneous (once weekly) formulations as separate programmes.

On receptor wording: the 2025 Lancet phase 1 papers (under the name amycretin) describe a GLP-1 and amylin receptor agonist (PMID 40550229 (opens in a new tab), PMID 40550231 (opens in a new tab)). The 2026 phase 2 abstracts add calcitonin receptors to the description (PMID 42532080 (opens in a new tab), PMID 42532079 (opens in a new tab)). Both descriptions refer to the same molecule; this page follows the newer, broader wording.

Unlike CagriSema (two peptides: cagrilintide + semaglutide), zenagamtide is one molecule with both incretin and amylin-pathway biology. No approval and no PubChem CID were identified; secondary CAS listings conflict (3005889-81-3 vs 3051672-09-1) and remain unverified.

How it compares (high level)

Clinical development (selected)

Early / PoC (often still listed as NNC0487-0111)

Phase 3 (zenagamtide / NNC0487-0111 naming mixed on CT.gov)

Key human results (peer-reviewed)

Keep obesity PoC and T2D phase 2 — and oral vs SC — in separate buckets.

Obesity proof-of-concept (published under amycretin name)

Oral phase 1 (Gasiorek et al., Lancet 2025; NCT05369390): exploratory weight summaries around −10.4% (up to 50 mg) and −13.1% (up to 2×50 mg) versus about −1.2% placebo at 12 weeks; GI events dose-related, mostly mild–moderate.

Subcutaneous phase 1b/2a (Dahl et al., Lancet 2025; NCT06064006): adherence-style estimates included about −24.3% at 60 mg / 36 weeks versus −1.1% placebo, with lower-dose arms over shorter durations also showing large PoC signals. Discontinuations were common; many not TEAE-related. Treat ~24% as early-phase PoC, not a phase 3 or label effect size.

Phase 2 type 2 diabetes (published under zenagamtide / formerly amycretin)

SC (PMID 42532080; NCT06542874): n=262 randomised; QW 0.4–40 mg; 36 weeks. HbA1c change from about −0.9% (0.4 mg) to −1.7% (40 mg); placebo-corrected ETD up to about −1.56%. GI most common; SAE 8%; no deaths reported in the paper framing.

Oral (PMID 42532079; same parent protocol): n=186; QD 6 / 25 / 50 mg; 36 weeks. HbA1c about −0.9 / −1.3 / −1.4% (ETD vs placebo about −0.5 / −0.99 / −1.09%). Dose-dependent GI.

Renal PK (PMID 42443140): single SC 0.3 mg; renal impairment did not meaningfully alter PK in that study’s framing — no dose adjustment proposed there.

Claims vs evidence

Related pages

• Legacy slug amycretin permanently redirects to this page
• Pramlintide, Cagrilintide, CagriSema, Semaglutide
• Eloralintide, Petrelintide

What this page intentionally omits

• Self-use oral or injectable protocols
• Mixing oral and SC trial arms into one regimen
• Treating PoC weight percentages as approved efficacy
• Unverified vendor CAS as primary identity