Overview
Cagrilintide is a long-acting synthetic analog of amylin — a pancreatic hormone co-secreted with insulin that regulates appetite, satiety, and gastric emptying. Unlike GLP-1 agonists (semaglutide, tirzepatide), cagrilintide targets the amylin receptor system, providing a complementary and distinct mechanism for weight management.
Novo Nordisk developed cagrilintide both as a standalone treatment and in fixed-dose combination with semaglutide, branded as CagriSema. The REDEFINE Phase III program — enrolling approximately 4,600 adults — produced the most significant weight loss results ever recorded for a non-surgical obesity intervention: 20.4% mean body weight reduction at 68 weeks with CagriSema, compared to 16.1% with semaglutide alone and 11.8% with cagrilintide alone.
Novo Nordisk filed the NDA with the FDA in December 2025. If approved, CagriSema would be the first injectable GLP-1 receptor agonist and amylin analog combination treatment. A dedicated Phase III monotherapy program (RENEW) for cagrilintide alone was announced in September 2025.
Dosage & Reconstitution
- Vial strength
- 5 mg
- BAC water added
- 3 mL
- Final concentration
- ~1.67 mg/mL
| Weeks | Dosage | Syringe units (U-100) |
|---|---|---|
| Weeks 1–2 | 0.6 mg | 36 units0.36 mL |
| Weeks 3–4 | 1.2 mg | 72 units0.72 mL |
| Weeks 5–6 | 2.4 mg | 144 units1.44 mL |
| Weeks 7–16 | 4.5 mg | 270 units2.7 mL |
- Vial strength
- 10 mg
- BAC water added
- 3 mL
- Final concentration
- ~3.33 mg/mL
| Weeks | Dosage | Syringe units (U-100) |
|---|---|---|
| Weeks 1–2 | 0.6 mg | 18 units0.18 mL |
| Weeks 3–4 | 1.2 mg | 36 units0.36 mL |
| Weeks 5–6 | 2.4 mg | 72 units0.72 mL |
| Weeks 7–16 | 4.5 mg | 135 units1.35 mL |
FrequencyOnce weekly, subcutaneous, on the same day each week.
Note
For review — the amounts are the trial's, the pace is not. Lau et al. (Lancet 2021) reached 4.5 mg once weekly by escalating over 20 weeks under supervision; the schedule in the chart reaches the same amount in six. The concentration strip above the chart is calculated from the vial and water volume and is correct.
The 4.5 mg endpoint is the top arm of the Phase 2 dose-ranging trial cited below, but that trial escalated to it over 20 weeks rather than the six charted here, so the pace is flagged for review while the amounts themselves are supported. Cagrilintide is a once-weekly amylin analogue that has never been approved as a standalone product, and the trial's escalation existed to manage nausea and vomiting — the early rows are tolerance steps, not smaller versions of the same treatment. Made up with 3 mL, a 5 mg vial is about 1.67 mg/mL and a 10 mg vial about 3.33 mg/mL, which puts the 4.5 mg amount at 270 units and 135 units respectively — both far more than the 0.5 mL a 50-unit syringe holds. Every amount from 1.2 mg upward is larger than one fill on the 5 mg vial, as are the 2.4 mg and 4.5 mg steps on the 10 mg vial, and each is marked. That is a property of a dilute research vial rather than of the trial, and it is the clearest sign that these figures are not a set of instructions.
Measurement note. At the water volumes above the largest amount in the chart comes to 270 units, which is more than the 1 mL a 100-unit U-100 syringe holds, so at this concentration the upper steps could not be drawn in a single fill at all.
What this evidence establishes. Cagrilintide has published Phase 2 human dose-ranging data as a once-weekly subcutaneous injection, escalated gradually. It has not been approved as a standalone product, and the trial doses were reached under supervised titration rather than started at.
Sources: Lau et al., Lancet 2021 — Phase 2 dose-ranging trial
For educational and laboratory research purposes only. It does not provide medical advice, dosing recommendations, or instructions for human or veterinary use. Syringe units assume a U-100 syringe, on which 1 mL is 100 units and a 50-unit syringe holds 0.5 mL.
Mechanism of Action
Cagrilintide and semaglutide target different but complementary pathways in the brain regions controlling appetite:
Amylin Receptor Activation
Binds AMY1 and AMY3 receptors in the area postrema and nucleus tractus solitarius — brain regions controlling satiety
Gastric Emptying
Slows gastric emptying, prolonging the feeling of fullness after meals — same mechanism as endogenous amylin
Glucagon Suppression
Reduces postprandial glucagon secretion, improving glycemic control — 73.5% of T2D patients reached HbA1c ≤6.5%
Dual Pathway Synergy
Combined with semaglutide (GLP-1), targets both hedonic and homeostatic appetite pathways in the hypothalamus and hindbrain
Long-Acting Design
Engineered for once-weekly dosing via albumin binding, unlike native amylin which has a half-life of minutes
Cardiometabolic Benefits
REDEFINE 1 showed improvements in blood pressure, waist circumference, lipids, and 88% normoglycemia in prediabetes
Research Timeline
Contraindications & Safety Data
CagriSema has the most robust Phase III safety database of any compound on this page — 4,600+ participants across the REDEFINE program. Safety data is extensive and well-characterized.
| Condition / Factor | Risk Level | Rationale |
|---|---|---|
| Medullary thyroid carcinoma (personal/family history) | HIGH | GLP-1 agonist component (semaglutide) carries boxed warning for thyroid C-cell tumors based on rodent studies |
| Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) | HIGH | Contraindicated due to GLP-1 component — consistent with all semaglutide products |
| Gastrointestinal adverse events | EXPECTED | 79.6% of CagriSema participants reported GI events (nausea, vomiting, diarrhea). Most were transient and mild-to-moderate. |
| Pregnancy / breastfeeding | HIGH | No safety data in pregnancy. Weight-loss medications are contraindicated during pregnancy. |
| Pancreatitis history | MODERATE | GLP-1 agonists carry a caution for pancreatitis. Monitoring recommended. |
| Severe renal impairment | MODERATE | GLP-1 agonists require caution in severe renal disease. CagriSema-specific data pending. |
| Gallbladder disease | MODERATE | Rapid weight loss from any cause increases gallstone risk. GLP-1 class effect. |
| Diabetic retinopathy | MODERATE | Rapid glycemic improvement may temporarily worsen pre-existing diabetic retinopathy |
Regulatory Status
FDA: NDA filed December 2025 for CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) for weight management. FDA review expected 2026. Not yet approved. Cannot be legally compounded, prescribed, or purchased as CagriSema.
Standalone cagrilintide: Phase III RENEW program initiated Q4 2025. No standalone NDA filed yet. Cagrilintide monotherapy is not available outside of clinical trials.
WADA: Amylin analogs are classified under S2 (peptide hormones and growth factors) on the WADA Prohibited List.
What this means: Cagrilintide represents the most clinically advanced amylin analog in history. Unlike most compounds on this site, it has robust Phase III data published in the NEJM and an active FDA submission. This is what the legitimate pharmaceutical pipeline looks like — contrast this with compounds that have zero human trials.
References (APA 7th Edition)
Cagrilintide Research Readiness Quiz
Test your understanding of cagrilintide and CagriSema's clinical evidence, mechanism, and regulatory trajectory.