Cagrilintide (AM833)

Long-Acting Amylin Receptor Agonist | Weight Loss & Diabetes

Weight: 4,409.01 Da
Half-life: ~7 days (159-195 hours)
Chain: 37 amino acids
3 studies
2025 latest
2 recent
Extensively Studied
Dose 2.4mg weekly (after escalation)
Frequency Once weekly, same day each week
Cycle Continuous long-term therapy
Storage Lyophilized: -20°C frozen; Reconstituted: 2-8°C refrigerated, use within 30 days
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Community Research

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Novel long-acting lipidated amylin analog functioning as dual amylin and calcitonin receptor agonist for weight management and type 2 diabetes. Phase 3 trials demonstrate 22.7% weight loss with CagriSema combination.

Mechanism of Action

Subcutaneous injection enables optimal bioavailability, targeting dual amylin and calcitonin receptors for satiety and metabolic regulation. Enhances insulin sensitivity and controls gastric emptying.

01 FDA development candidate with extensive Phase 3 data
02 Superior weight loss in combination with semaglutide (22.7%)
03 Once-weekly convenience
04 2.2% HbA1c reduction with CagriSema

Molecular Data

Molecular Weight
4,409.01 Da
Chain Length
37 amino acids
Type
Amylin receptor agonist
Amino Acid Sequence
37-amino acid peptide

Complex or non-standard sequence format

Peak 0.0 mcg
Trough 0.0 mcg
SS Peak 0.0 mcg
SS Trough 0.0 mcg

Research Indications

Weight Loss
Obesity (Monotherapy) effective

Phase 3 trials demonstrate significant weight loss.

Obesity (CagriSema Combination) most effective

22.7% weight loss with CagriSema combination, surpassing existing therapies.

Weight Loss in Diabetic Patients most effective

15.7% weight loss in diabetic patients with concurrent glycemic improvements.

Metabolic
Glycemic Control most effective

2.2% HbA1c reduction with CagriSema versus semaglutide alone.

Insulin Sensitivity effective

Amylin receptor activation enhances insulin sensitivity and glucose metabolism.

Appetite Control
Satiety Enhancement effective

Dual pathway satiety via amylin and calcitonin receptor activation.

Dosing Protocols

Subcutaneous injection to abdomen, thigh, or upper arm. Pre-filled pen design when commercially available.

GoalDoseFrequencyRoute
Weight Loss (Monotherapy)2.4mgOnce weeklySubQ
Weight Loss (CagriSema)2.4mg + semaglutide 2.4mgOnce weeklySubQ
Type 2 Diabetes Management2.4mg weeklyOnce weeklySubQ with metformin
Dose Escalation Protocol0.25mg → 0.5mg → 1.0mg → 1.7mg → 2.4mgWeekly increases over 16 weeksSubQ

Reconstitution Instructions

Materials Needed:
  • Bacteriostatic water (standard BAC water acceptable for <30 days)
  • Optional: 0.6% acetic acid to adjust pH to ~4.0
  • Insulin syringes
  • Alcohol swabs
  1. 1 CRITICAL: Requires acidic pH (3.5-4.5) to prevent fibril formation
  2. 2 Reconstitute slowly down vial side; swirl gently (do not shake)
  3. 3 Verify pH 3.5-4.5 after reconstitution
  4. 4 Solution must be clear—discard if cloudy or particulate
  5. 5 Store refrigerated (2-8°C); inspect before each injection
  6. 6 Allow 15-30 minutes to reach room temperature before injection
  7. 7 Rotate injection sites weekly

Interactions

++
Semaglutide
CagriSema combination achieves enhanced weight loss through complementary GLP-1 and amylin pathways.
synergistic
+
Tirzepatide
No known direct interactions; different mechanisms allow concurrent use.
compatible
~
Retatrutide
Compounded GI side effects create substantial risk without specialist supervision.
monitor
+
Metformin
Well-tolerated in Phase 2/3 trials with no pharmacokinetic interactions.
compatible
+
SGLT2 Inhibitors
Clinical trials demonstrated safe concurrent use with complementary mechanisms.
compatible
!
Pramlintide
Both are amylin agonists; combination provides no additional benefit and increases GI risks.
avoid
~
Oral Contraceptives
Delayed gastric emptying may affect absorption; space administration by 1 hour.
monitor

What to Expect

Week 1-2
Gastrointestinal adaptation; mild nausea possible during dose escalation
Week 4-8
Early weight loss (2-5%); noticeable appetite reduction
Week 12-26
Significant weight loss acceleration (10-15%); improved satiety signals
Week 26+
Peak efficacy (15-23% weight loss); sustained maintenance with continued therapy

Side Effects & Safety

Common Side Effects

  • Gastrointestinal effects (nausea, vomiting, diarrhea) during initial weeks
  • Anti-cagrilintide antibodies develop in 46-73% but do not affect efficacy
  • Only 57.3% achieved maximum 2.4mg dose in REDEFINE 1 trial

Stop Signs - Discontinue if:

  • Severe persistent nausea/vomiting preventing hydration
  • Pancreatitis signs (severe abdominal pain radiating to back)
  • Severe allergic reactions or anaphylaxis
  • Significant injection site reactions or abscess formation

Contraindications

  • Not recommended in pregnancy or breastfeeding
  • Not yet commercially available (FDA approval expected Q1 2026)

Quality Checklist

Good Signs

  • Pre-filled pen design when approved
  • Pharmaceutical grade purity >98%
  • Frozen storage stability at -20°C
  • Extended stability over 7-day dosing interval

Warning Signs

  • Standard bacteriostatic water acceptable short-term but may degrade at neutral pH; optimal stability requires pH ~4.0

Bad Signs

  • Fibril formation at improper pH—solution must remain clear
  • Aggregation or precipitation indicates degradation

References

  • Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity
    Novo Nordisk REDEFINE 1 Investigators
    New England Journal of Medicine (2025)

    Phase 3a REDEFINE 1 trial: 3,417 adults without diabetes. Estimated mean weight loss -20.4% with CagriSema vs -3.0% placebo at 68 weeks. GI adverse events in 79.6% of treatment group, mainly transient and mild-to-moderate.

  • Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes
    Novo Nordisk REDEFINE 2 Investigators
    New England Journal of Medicine (2025)

    Phase 3a REDEFINE 2 trial: Adults with BMI ≥27, HbA1c 7-10%, and type 2 diabetes. Mean weight loss -13.7% with CagriSema vs -3.4% placebo at 68 weeks. Significant improvements in glycemic measures.

  • Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial
    Frias JP, Deenadayalan S, Erichsen L, Knop FK, Lingvay I, Machineni S, Mathieu C, Pedersen SD, Davies M
    The Lancet (2023)

    32-week phase 2 trial at 17 US sites. CagriSema showed greater weight loss vs semaglutide or cagrilintide alone. HbA1c improvements significant. Well tolerated with predominantly GI adverse events.

Related Peptides

Semaglutide synergistic

CagriSema combination achieves enhanced weight loss through complementary GLP-1 and amylin pathways.

Tirzepatide compatible

No known direct interactions; different mechanisms allow concurrent use.

Disclaimer

This information is for educational and research purposes only. Consult a healthcare professional before use.