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FAT LOSSPhase IIIAMYLIN ANALOGWEIGHT LOSSOBESITY

Petrelintide

Also known as: ZP8396

13 views/week 0 citations 0 edits Updated 9/22/2026

Petrelintide is a long-acting amylin analog from Zealand Pharma, partnered with Roche, dosed once weekly by subcutaneous injection. It delivered double-digit weight loss with placebo-like tolerability in the Phase 2 ZUPREME-1 trial, and moved into Phase 3 for chronic weight management in the second half of 2026.

STRUCTURE

Molecular Composition

FORMULA
C₁₈₅H₃₀₅N₄₉O₆₁
MOL. WEIGHT
~4,191.76 Da (calc.)
CAS NUMBER
2766385-23-1
SEQUENCE LENGTH
36 amino acids
TARGET
Amylin receptor
ROUTE
Subcutaneous, weekly
AMINO ACID CHAIN VISUALIZATION
A
Amylin backbone
36-residue human amylin analog
NH-CO
K
Acylation site
fatty-acid chain for albumin binding
NH-CO
S
Stability region
engineered against fibrillation near neutral pH
NH-CO
R
Receptor contact
amylin receptor engagement
NH-CO
C
Disulfide motif
conserved amylin ring structure
SEQUENCEA-K-S-R-C
MECHANISMS

How It Works

🎯
Amylin Receptor Agonism
Amylin is co-secreted with insulin from pancreatic beta cells after eating. Agonising its receptor slows gastric emptying and promotes satiety through a pathway entirely separate from GLP-1.
🧠
Leptin Re-Sensitisation
Amylin receptor activation is understood to restore sensitivity to leptin, the satiety hormone that obesity blunts — producing fullness earlier in a meal rather than simply suppressing appetite.
🧪
Fibrillation-Resistant Design
Native amylin aggregates readily, which has historically limited it as a drug. Petrelintide is engineered for stability near neutral pH, which both enables once-weekly dosing and allows co-formulation with other peptides.
🔀
A Non-Incretin Mechanism
Every high-efficacy approved weight-management drug works through GLP-1 or GIP/GLP-1. Petrelintide is a test of whether the amylin pathway can reach similar efficacy with a different, potentially better-tolerated side-effect profile.
OVERVIEW

Research Overview

Petrelintide pursues weight loss through amylin receptor agonism rather than the GLP-1 or dual GIP/GLP-1 mechanisms behind every high-efficacy weight-management drug currently approved. The headline claim from Phase 2 is not raw efficacy but tolerability: double-digit weight reduction with a side-effect profile the company describes as placebo-like, which if it holds in Phase 3 would matter, since GI intolerance drives much of the real-world discontinuation seen with incretin drugs.

It is engineered for chemical and physical stability with no fibrillation near neutral pH — a practical property that allows co-formulation with other peptides, and the reason it is being positioned as a combination backbone as well as a monotherapy. Not yet approved.

Mechanism of Action

// AMYLIN RECEPTOR AGONISM

Amylin is co-secreted with insulin from pancreatic beta cells in response to nutrients. Agonising its receptor slows gastric emptying and promotes satiety, and is understood to restore sensitivity to leptin — producing fullness earlier in a meal through a pathway independent of GLP-1.

// FATTY-ACID ACYLATION

Acylation drives albumin binding, extending the circulating half-life enough to support once-weekly subcutaneous dosing.

DOSAGE

Dosage & Administration

INJECTABLE (SUBCUTANEOUS) — PHASE 2 ZUPREME-1
DOSE
Dose-escalated (specific Phase 3 regimen not yet published)
FREQUENCY
Once weekly
NOTES
Phase 2 reported double-digit weight loss with tolerability described as placebo-like. The Phase 3 programme began in H2 2026; final dosing has not been published.

Investigational and not commercially available. The interesting claim here is tolerability rather than peak efficacy — GI side effects drive much real-world discontinuation of incretin drugs, so an amylin agonist that avoids them could matter even at comparable weight loss.

CYCLING

Cycle Duration Guide

ON CYCLE
Continuous weekly dosing (chronic weight-management model)
OFF CYCLE
Not established — no approved discontinuation protocol

As with other weight-management agents, weight regain on discontinuation is expected but not yet characterised for this compound.

Investigational — Phase 3 only, not approved. No verified consumer source exists.

NOTES

Research Notes

Investigational, Phase 3 (initiated H2 2026) for chronic weight management. The full amino acid sequence has not been publicly disclosed; it is described as a 36-residue acylated analog of human amylin. Molecular weight here is derived from the published molecular formula.

Quick Reference
FORMULAC₁₈₅H₃₀₅N₄₉O₆₁
MOL. WEIGHT4,191.76 Da
LENGTH36 amino acids
ORIGINSynthetic amylin analog (Zealand Pharma, partnered with Roche)
HALF-LIFELong-acting — supports once-weekly subcutaneous dosing
SOLUBILITYNot publicly disclosed
CAS NO.2766385-23-1
STATUSPhase III
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TAGS
amylin analogweight lossobesityonce-weeklyZealand PharmaRoche