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FAT LOSSPhase IIIAMYLIN ANALOGUEWEIGHT LOSSOBESITY

Cagrilintide

Also known as: AM833 · CagriSema (combined with semaglutide)

18.6k views/week 124 citations 8 edits Updated 4/6/2026

Cagrilintide (AM833) is a long-acting amylin analogue developed by Novo Nordisk. It mimics the satiety and gastric-emptying effects of endogenous amylin through calcitonin receptor activation. In combination with semaglutide as CagriSema, Phase 3 data showed up to 22.7% weight loss — approaching efficacy seen with triple agonists.

STRUCTURE

Molecular Composition

FORMULA
C₁₅₃H₂₄₉N₄₃O₄₉S₂ (approx)
MOL. WEIGHT
~3368 Da
SEQUENCE LENGTH
37 amino acids
CAS NUMBER
2381809-25-0
TARGET
Amylin / Calcitonin Receptor
HALF-LIFE
~7–10 days (weekly)
AMINO ACID CHAIN VISUALIZATION
K
Lys (N-term mod)
fatty acid anchor
NH-CO
C
Cys
disulfide bridge
NH-CO
N
Asn
amylin receptor contact
NH-CO
T
Thr
receptor binding
NH-CO
A
Ala
backbone stability
NH-CO
T
Thr
C-terminal region
NH-CO
C
Cys
disulfide bridge partner
SEQUENCEK-C-N-T-A-T-C
MECHANISMS

How It Works

🧠
Amylin / Calcitonin Receptor Agonism
Cagrilintide activates amylin receptors (CALCR + RAMP1/2/3 complexes) in the brainstem area postrema and nucleus tractus solitarius — regions outside the blood-brain barrier that directly receive peripheral satiety signals. This triggers satiety, reduces meal size, and prolongs inter-meal intervals through circuits distinct from GLP-1 hypothalamic pathways.
📉
Additive Satiety with GLP-1 (CagriSema)
Amylin and GLP-1 receptors are expressed in different CNS regions with complementary circuits. Phase 3 CagriSema data shows ~6.6 percentage points additional weight loss vs. semaglutide alone — confirming meaningful additive satiety signaling when both pathways are engaged simultaneously.
🔬
Gastric Emptying & Glucagon Suppression
Like native amylin, cagrilintide slows gastric emptying and suppresses post-prandial glucagon — extending the period of satiety after meals and attenuating glucose excursions. These effects are independent of GLP-1 mechanisms and provide complementary glycemic benefit in the CagriSema combination.
⏱️
Extended Half-life Engineering
Native amylin has a half-life of ~15 minutes. Cagrilintide achieves 7–10 day half-life through fatty acid conjugation (C20 chain) enabling albumin binding — the same engineering strategy as semaglutide. Multiple amino acid substitutions also prevent the aggregation that makes native amylin difficult to formulate at therapeutic concentrations.
OVERVIEW

Research Overview

Amylin is a peptide hormone co-secreted with insulin from pancreatic beta cells in response to meals. It plays a critical role in post-prandial glucose regulation by slowing gastric emptying, suppressing post-meal glucagon, and signaling satiety through brainstem receptors.

Cagrilintide (AM833) is a fatty acid-modified amylin analogue engineered for once-weekly dosing. As a monotherapy, cagrilintide achieved 10.8% weight loss over 26 weeks in Phase 2 trials. Its combination with semaglutide (CagriSema) achieved 22.7% weight loss at 68 weeks in REDEFINE-1 Phase 3 trial (2024).

Mechanism of Action

// AMYLIN / CALCITONIN RECEPTOR AGONISM

Cagrilintide activates amylin receptors (CALCR + RAMP1/2/3 complexes) in the area postrema and nucleus tractus solitarius — regions outside the blood-brain barrier. Receptor activation suppresses food intake, reduces meal size, and prolongs inter-meal intervals.

// GASTRIC EMPTYING MODULATION

Like native amylin, cagrilintide slows gastric emptying in a meal-dependent fashion, attenuating post-prandial glucose excursions and prolonging fullness — mechanistically distinct from GLP-1 effects.

// GLUCAGON SUPPRESSION

Amylin receptor activation suppresses post-prandial glucagon release from alpha cells, reducing hepatic glucose output in the post-meal state.

SEQUENCE

Amino Acid Sequence

Modified 37-AA amylin analogue (C20 fatty acid conjugated for weekly dosing)
DOSAGE

Dosage & Administration

INJECTABLE (SUBCUTANEOUS) — MONOTHERAPY
DOSE
0.16 mg → 0.3 mg → 0.6 mg → 1.2 mg → 2.4 mg → 4.5 mg
FREQUENCY
Once weekly; escalate every 4 weeks
NOTES
Phase 2 monotherapy protocol. Top dose of 4.5 mg achieved ~11% weight loss over 26 weeks. Inject into abdomen, thigh, or upper arm. Refrigerate pen — do not freeze.
INJECTABLE (SUBCUTANEOUS) — CAGRISEMA COMBINATION
DOSE
Cagrilintide 2.4 mg + Semaglutide 2.4 mg (co-formulated)
FREQUENCY
Once weekly (single injection, fixed combination)
NOTES
Phase 3 REDEFINE program. Co-formulated fixed-ratio combination pen. Dose is escalated over 32 weeks following a structured titration schedule. CagriSema is intended as the Phase 3 / commercial formulation — not combined from separate vials.

Cagrilintide adds an amylin-pathway satiety mechanism on top of GLP-1 agonism (when used as CagriSema). Phase 3 REDEFINE-1 showed 22.7% weight loss — approaching retatrutide levels. Side effects are predominantly GI (nausea, vomiting) during escalation, consistent with amylin and GLP-1 class effects. Not currently commercially available as monotherapy; awaiting NDA submission expected ~2025.

CYCLING

Cycle Duration Guide

ON CYCLE
Continuous chronic use (designed for long-term weight management)
OFF CYCLE
No established off-cycle protocol. Weight regain expected upon discontinuation.

As a component of CagriSema, cagrilintide shares the chronic-use model of GLP-1 agonists. The amylin pathway provides complementary satiety signaling that may produce more durable appetite regulation than GLP-1 alone, but discontinuation data from Phase 3 are not yet publicly available. Like semaglutide, long-term use is the intended clinical model.

Class warnings apply from the semaglutide component when used as CagriSema. Avoid in MTC/MEN2 history. Pancreatitis risk. Not approved for use in pregnancy.

NOTES

Research Notes

Phase 2 monotherapy: 10.8% weight loss at 4.5 mg/week over 26 weeks. Phase 3 REDEFINE-1 (CagriSema 2.4/2.4 mg): 22.7% weight loss at 68 weeks vs. 16.1% for semaglutide alone. NDA submission anticipated 2025.

Quick Reference
FORMULAC₁₅₃H₂₄₉N₄₃O₄₉S₂ (approx)
MOL. WEIGHT3,367.8 Da
LENGTH37 amino acids
ORIGINSynthetic amylin analogue (Novo Nordisk); modified for weekly dosing
HALF-LIFE~7–10 days (weekly dosing)
SOLUBILITYWater-soluble; solution for injection
CAS NO.2381809-25-0
STATUSPhase III
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TAGS
amylin analogueweight lossobesitysatietyGLP-1 combo