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Cagrilintide

Extensively Studied

Long-Acting Amylin Receptor Agonist | Weight Loss & Diabetes

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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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.

Key Benefits

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

Weight Loss

  • Obesity (Monotherapy)

    Phase 3 trials demonstrate significant weight loss.

  • Obesity (CagriSema Combination)

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

  • Weight Loss in Diabetic Patients

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

Metabolic

  • Glycemic Control

    2.2% HbA1c reduction with CagriSema versus semaglutide alone.

  • Insulin Sensitivity

    Amylin receptor activation enhances insulin sensitivity and glucose metabolism.

Appetite Control

  • Satiety Enhancement

    Dual pathway satiety via amylin and calcitonin receptor activation.

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
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
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

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)

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
  • REDEFINE 1 Trial - Phase 3 Weight Loss
    (2025)

    3,417 adults with obesity; 22.7% weight loss with CagriSema vs 2.4% placebo. New England Journal of Medicine.

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

    1,206 adults; 15.7% weight loss; 73.5% achieved HbA1c ≤6.5%. New England Journal of Medicine.

  • Phase 2 Type 2 Diabetes Combination Study
    (2023)

    32 weeks; 15.6% weight loss; 2.2% HbA1c reduction with CagriSema. The Lancet.

Disclaimer

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