Well Researched

Cagrilintide

Long-Acting Amylin Receptor Agonist | Weight Loss & Diabetes

Cagrilintide (AM833) is a novel long-acting lipidated amylin analog that acts as a dual amylin and calcitonin receptor agonist. Developed for weight management and type 2 diabetes treatment, it shows superior weight loss potential when combined with semaglutide (CagriSema), with recent Phase 3 trials demonstrating up to 22.7% weight reduction.

Daily dose

2.4 mg weekly

Frequency

Once weekly

Cycle length

Continuous

Storage

-20°C

Key benefits

FDA development candidate, extensive Phase 3 data, superior weight loss in combination with semaglutide, once-weekly convenience

How it works

Subcutaneous injection provides optimal bioavailability of lipidated amylin analog, targeting dual amylin and calcitonin receptors for satiety and metabolic effects

Dosage protocols

Goal

Weight Loss (Monotherapy)

Dose

2.4 mg weekly · Once weekly

Route

Subcutaneous injection

Goal

Weight Loss (CagriSema)

Dose

2.4 mg + semaglutide 2.4 mg · Once weekly

Route

Subcutaneous injection

Goal

Type 2 Diabetes Management

Dose

2.4 mg weekly · Once weekly

Route

Subcutaneous injection with metformin

Goal

Dose Escalation Protocol

Dose

0.25 mg → 0.5 mg → 1.0 mg → 1.7 mg → 2.4 mg · Weekly increases over 16 weeks

Route

Subcutaneous injection

Goal

Combination Diabetes Therapy

Dose

2.4 mg + SGLT2 inhibitor · Once weekly

Route

Subcutaneous injection

Goal

Cardiovascular Risk Reduction

Dose

2.4 mg weekly · Once weekly

Route

Subcutaneous injection (REDEFINE 3 trial)

Research indications

weight Loss

Superior Obesity Treatment — Phase 3 trials demonstrate 22.7% weight loss with CagriSema combination, outperforming existing therapies

Type 2 Diabetes Weight Management — 15.7% weight loss in diabetic patients with concurrent glycemic improvements

Sustained Weight Maintenance — Long-acting formulation supports sustained weight loss throughout treatment period

metabolic

Glucose Control Enhancement — Phase 2 trials show 2.2% HbA1c reduction with CagriSema combination versus semaglutide alone

Insulin Sensitivity Improvement — Amylin receptor activation enhances insulin sensitivity and glucose metabolism

Gastric Emptying Regulation — Controlled gastric emptying improves postprandial glucose control and satiety

appetite Control

Dual Pathway Satiety — Amylin and calcitonin receptor activation provides robust appetite suppression via hindbrain pathways

Food Preference Modulation — Central nervous system effects influence food choices and eating behaviors

Early Satiation Induction — Promotes feeling of fullness with smaller meal portions, supporting caloric restriction

Administration

injectable

Interactions

Synergistic

Semaglutide — CagriSema combination demonstrates enhanced weight loss (22.7% vs 16.1% semaglutide alone) and improved glycemic control through complementary GLP-1 and amylin pathways.

Compatible

Tirzepatide — No known direct interactions. Both are effective weight loss agents with different mechanisms - cagrilintide targets amylin/calcitonin receptors while tirzepatide targets GLP-1/GIP receptors.

Use Caution

Retatrutide — Both cause significant GI effects (gastroparesis, nausea). Cagrilintide (amylin agonist) and Retatrutide (triple GLP-1/GIP/glucagon agonist) have different mechanisms but compounded GI side effects create substantial risk. Not recommended without specialist supervision.

Compatible

Liraglutide — Phase 2 trials show similar efficacy profiles with no adverse interactions. Both GLP-1 agonists and amylin analogs work through distinct satiety pathways.

Monitor Combination

Insulin — Monitor glucose levels closely as cagrilintide affects gastric emptying and may alter insulin absorption timing. May require insulin dose adjustments in diabetic patients.

Compatible

Metformin — Well-tolerated combination demonstrated in Phase 2/3 trials. No pharmacokinetic interactions observed between cagrilintide and metformin.

Compatible

SGLT2 Inhibitors — Clinical trials included patients on SGLT2 inhibitors with no safety concerns. Both mechanisms complement each other for diabetes and weight management.

Avoid Combination

Pramlintide — Both are amylin receptor agonists with overlapping mechanisms. Combination would provide no additional benefit and may increase risk of gastrointestinal side effects.

Requires Timing

Oral Contraceptives — Delayed gastric emptying may affect absorption of oral contraceptives. Space administration by 1 hour before cagrilintide injection.

Safety notes

Most common side effects are gastrointestinal (nausea, vomiting, diarrhea) during initial weeks

Anti-cagrilintide antibodies develop in 46-73% of patients but do not affect efficacy

No clinically significant QT prolongation observed in thorough QT studies

Only 57.3% of patients achieved maximum 2.4 mg dose in REDEFINE 1 trial

Research studies

REDEFINE 1 Trial - Phase 3 Weight Loss (2025)

Humans | 2.4 mg weekly | 68 weeks | 22.7% weight loss vs 2.4% placebo

Landmark Phase 3 trial published in NEJM demonstrating superior weight loss with CagriSema combination in 3,417 adults with obesity, achieving primary endpoints with excellent safety profile

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REDEFINE 2 Trial - Phase 3 Type 2 Diabetes (2025)

Humans | 2.4 mg weekly | 68 weeks | 15.7% weight loss, 73.5% achieved HbA1c ≤6.5%

Phase 3 trial in 1,206 adults with type 2 diabetes and obesity published in NEJM, demonstrating significant weight loss and glycemic improvements with CagriSema

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Thorough QT Study - Cardiac Safety (2024)

Humans | 4.5 mg single dose | 5 days | No clinically relevant QTc prolongation

Dedicated cardiac safety study confirming no significant QT interval prolongation at supratherapeutic doses, supporting cardiovascular safety profile

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Phase 2 Type 2 Diabetes Combination Study (2023)

Humans | 2.4 mg weekly | 32 weeks | 15.6% weight loss, 2.2% HbA1c reduction with CagriSema

First study reporting efficacy of GLP-1/amylin combination in type 2 diabetes, showing superior weight loss and glycemic control versus individual components

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Phase 2 Dose-Finding Monotherapy Trial (2021)

Humans | 0.3-4.5 mg weekly | 26 weeks | Up to 10.8% weight loss dose-dependent

Multi-center dose-finding trial in 706 participants demonstrating dose-dependent weight loss and establishing optimal 2.4 mg weekly dosing

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Phase 1b Safety and Pharmacokinetics Study (2021)

Humans | 0.16-4.5 mg weekly | 20 weeks | Safety profile established

First-in-human combination study with semaglutide demonstrating acceptable safety profile and pharmacokinetic parameters for CagriSema development

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Related compounds

Semaglutide Tirzepatide Adipotide (Prohibitin‑TP01)Tesofensine