Cagrilintide
Long-Acting Amylin Receptor Agonist · Weight Loss & Diabetes
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.
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.
Subcutaneous injection enables optimal bioavailability, targeting dual amylin and calcitonin receptors for satiety and metabolic regulation. Enhances insulin sensitivity and controls gastric emptying.
Research indications
What the compound has been studied for, grouped by body system. Effect size is the reported magnitude where it was measured — not a recommendation.
Phase 3 trials demonstrate significant weight loss.
22.7% weight loss with CagriSema combination, surpassing existing therapies.
15.7% weight loss in diabetic patients with concurrent glycemic improvements.
2.2% HbA1c reduction with CagriSema versus semaglutide alone.
Amylin receptor activation enhances insulin sensitivity and glucose metabolism.
Dual pathway satiety via amylin and calcitonin receptor activation.
A large effect in a weak study and a small effect in a strong one are different things. Effect size is never evidence of use in people.
- Class
- Amylin receptor agonist
- Chain length
- 37 residues
- Molecular weight
- 4409.01 Da
- Half-life
- ~168 h
- Typical dose
- 2.4mg weekly (after escalation)
- Frequency
- Once weekly, same day each week
- Cycle length
- Continuous long-term therapy
- Storage
- Lyophilized: -20°C frozen; Reconstituted: 2-8°C refrigerated, use within 30 days
Molecular data
- Type
- Amylin receptor agonist
- Molecular weight
- 4409.01 Da
- Chain length
- 37 residues
- Half-life
- 10080 min
Dosing reference
Doses reported in the literature and by suppliers. These are a record of what has been used in research — reference, never instruction.
| Context | Route | Amount | Frequency |
|---|---|---|---|
| Weight Loss (Monotherapy) | SubQ | 2.4mg | Once weekly |
| Weight Loss (CagriSema) | SubQ | 2.4mg + semaglutide 2.4mg | Once weekly |
| Type 2 Diabetes Management | SubQ with metformin | 2.4mg weekly | Once weekly |
| Dose Escalation Protocol | SubQ | 0.25mg → 0.5mg → 1.0mg → 1.7mg → 2.4mg | Weekly increases over 16 weeks |
Interactions
CagriSema combination achieves enhanced weight loss through complementary GLP-1 and amylin pathways.
No known direct interactions; different mechanisms allow concurrent use.
Compounded GI side effects create substantial risk without specialist supervision.
Well-tolerated in Phase 2/3 trials with no pharmacokinetic interactions.
Clinical trials demonstrated safe concurrent use with complementary mechanisms.
Both are amylin agonists; combination provides no additional benefit and increases GI risks.
Delayed gastric emptying may affect absorption; space administration by 1 hour.
Quality checklist
- ✓Pre-filled pen design when approved
- ✓Pharmaceutical grade purity >98%
- ✓Frozen storage stability at -20°C
- ✓Extended stability over 7-day dosing interval
- !Standard bacteriostatic water acceptable short-term but may degrade at neutral pH; optimal stability requires pH ~4.0
- ×Fibril formation at improper pH—solution must remain clear
- ×Aggregation or precipitation indicates degradation
What to expect
Safety
- 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
- 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
- Not recommended in pregnancy or breastfeeding
- Not yet commercially available (FDA approval expected Q1 2026)
FAQ
How much weight loss can I expect from CagriSema combination therapy?
Phase 3 REDEFINE trials showed estimated mean weight loss of -20.4% at 68 weeks without diabetes vs -3% placebo. In diabetic patients, CagriSema achieved -13.7% weight loss vs -3.4% placebo. These are the most dramatic weight loss results seen with any approved or experimental therapy to date.
Why do 46-73% of people develop anti-cagrilintide antibodies, and does it matter?
Anti-cagrilintide antibodies develop in roughly half of users, likely due to the peptide being foreign. Remarkably, clinical trial data showed these antibodies do NOT reduce efficacy—weight loss continues despite antibody formation. This unusual finding suggests the antibodies don't significantly neutralize the therapeutic effect.
Why is pH so critical when reconstituting cagrilintide?
Cagrilintide's peptide structure is prone to fibril formation and aggregation at neutral pH. Maintaining pH 3.5-4.5 prevents this self-assembly into inactive clumps. Solution must remain clear; any cloudiness or particles indicate degradation, and the dose should be discarded to avoid injecting aggregated, potentially less potent or harmful material.
When will cagrilintide be available and can I get it now?
Cagrilintide is not yet commercially available. FDA approval is expected Q1 2026. Current access is limited to clinical trial participants. Anyone claiming to sell cagrilintide now is offering an unapproved, likely research-grade product of unknown quality and purity.
References
- 1Efficacy 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 trialFrias 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.
human-rctPubMed 37364590 ↗ - 2Coadministered Cagrilintide and Semaglutide in Adults with Overweight or ObesityNovo 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.
reviewPubMed 40544433 ↗ - 3Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 DiabetesNovo 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.
reviewPubMed 40544432 ↗