Cagrilintide
Also known as: AM833
Long-Acting Amylin Receptor Agonist | Weight Loss & Diabetes
Overview
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.
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
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.
Molecular data
- Type
- Amylin receptor agonist
- Half-life
- ~7 days (159-195 hours)
Sequence
37-amino acid peptide
Indications
What the research community uses this compound for, with self-reported effectiveness.
Weight Loss
Obesity (Monotherapy)
EffectivePhase 3 trials demonstrate significant weight loss.
Obesity (CagriSema Combination)
Most effective22.7% weight loss with CagriSema combination, surpassing existing therapies.
Weight Loss in Diabetic Patients
Most effective15.7% weight loss in diabetic patients with concurrent glycemic improvements.
Metabolic
Glycemic Control
Most effective2.2% HbA1c reduction with CagriSema versus semaglutide alone.
Insulin Sensitivity
EffectiveAmylin receptor activation enhances insulin sensitivity and glucose metabolism.
Appetite Control
Satiety Enhancement
EffectiveDual pathway satiety via amylin and calcitonin receptor activation.
Dosing protocols
Common protocols by delivery method. Adjust the curve below to model accumulation in your own cycle.
Injectable
Subcutaneous injection to abdomen, thigh, or upper arm. Pre-filled pen design when commercially available.
| Protocol | Dose | Frequency | Route / duration |
|---|---|---|---|
| Weight Loss (Monotherapy) | 2.4mg | Once weekly | SubQ |
| Weight Loss (CagriSema) | 2.4mg + semaglutide 2.4mg | Once weekly | SubQ |
| Type 2 Diabetes Management | 2.4mg weekly | Once weekly | SubQ with metformin |
| Dose Escalation Protocol | 0.25mg → 0.5mg → 1.0mg → 1.7mg → 2.4mg | Weekly increases over 16 weeks | SubQ |
Preparation
You will need
- Bacteriostatic water (standard BAC water acceptable for <30 days)
- Optional: 0.6% acetic acid to adjust pH to ~4.0
- Insulin syringes
- Alcohol swabs
Steps
- CRITICAL: Requires acidic pH (3.5-4.5) to prevent fibril formation
- Reconstitute slowly down vial side; swirl gently (do not shake)
- Verify pH 3.5-4.5 after reconstitution
- Solution must be clear—discard if cloudy or particulate
- Store refrigerated (2-8°C); inspect before each injection
- Allow 15-30 minutes to reach room temperature before injection
- Rotate injection sites weekly
Work out the water volume and syringe units in the reconstitution calculator →
Interactions
Pairwise interactions with other compounds you might be cycling — the same data behind the cycle builder's safety check.
Pramlintide
AvoidBoth are amylin agonists; combination provides no additional benefit and increases GI risks.
Retatrutide
MonitorCompounded GI side effects create substantial risk without specialist supervision.
Oral Contraceptives
MonitorDelayed gastric emptying may affect absorption; space administration by 1 hour.
Semaglutide
SynergisticCagriSema combination achieves enhanced weight loss through complementary GLP-1 and amylin pathways.
Tirzepatide
CompatibleNo known direct interactions; different mechanisms allow concurrent use.
Metformin
CompatibleWell-tolerated in Phase 2/3 trials with no pharmacokinetic interactions.
SGLT2 Inhibitors
CompatibleClinical trials demonstrated safe concurrent use with complementary mechanisms.
Timeline
Typical week-by-week effects reported in clinical and observational data.
- 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
Safety
Reported adverse effects, contraindications, and what to monitor on cycle.
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 — stop and seek advice
- 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)
Monitoring
- No clinically significant QT prolongation observed
- Monitor for fibril formation in reconstituted solution (must remain clear)
Quality checks
What a legitimate product looks like, what should give pause, and what should make you stop.
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
Stop signs — don't use
- Fibril formation at improper pH—solution must remain clear
- Aggregation or precipitation indicates degradation
Recent research
Newer papers and trial readouts on file for this compound, with source and date.
December 2025 · Hypertension
CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1
REDEFINE 1 post-hoc analysis: CagriSema showed clinically relevant BP reductions (systolic -10.9 vs -2.8 mmHg placebo; diastolic -5.4 vs -1.7 mmHg) across wide range of subgroups including resistant hypertension.
2025 · Molecular Metabolism
CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure
Mechanistic study demonstrating CagriSema drives weight loss primarily through reduced energy intake while preserving energy expenditure, differentiating it from caloric restriction alone.
References
Primary literature and clinical-trial data informing this entry.
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.
Last updated . How this page was sourced is described in the methodology.