Cagrilintide vs Semaglutide
Comparing Novo Nordisk's long-acting amylin analog cagrilintide with GLP-1 agonist semaglutide - and their combination (CagriSema).
Last updated: February 1, 2026
Dossier labels summarize each dossier's research scope. They do not establish comparative treatment benefit or safety. Read the comparison below in that context.
Cagrilintide
Dossier overview
Semaglutide
Dossier overview
Overview
Cagrilintide is Novo Nordisk’s investigational long-acting amylin analog, while semaglutide is an approved GLP-1 receptor agonist. These peptides work through different mechanisms and are being developed as a combination therapy (CagriSema) that may provide superior weight loss to either alone.
Mechanism Comparison
| Aspect | Cagrilintide | Semaglutide |
|---|---|---|
| Target | Amylin receptors (AMY1, AMY2, AMY3) | GLP-1 receptor |
| Natural Hormone | Amylin analog | GLP-1 analog |
| Primary Site | Area postrema (brainstem) | Hypothalamus, GI, pancreas |
| Half-life | ~160 hours | ~165 hours |
Why Different Mechanisms Matter
Cagrilintide (Amylin):
- Slows gastric emptying
- Reduces glucagon secretion
- Promotes satiety via brainstem signaling
- Distinct neuronal pathways from GLP-1
Semaglutide (GLP-1):
- Enhances insulin secretion
- Suppresses glucagon
- Appetite reduction via hypothalamus
- Delays gastric emptying
These complementary mechanisms support the combination approach.
Evidence Comparison
| Aspect | Cagrilintide | Semaglutide |
|---|---|---|
| Development Phase | Phase 3 (as CagriSema) | FDA Approved |
| Standalone Trials | Phase 2 completed | STEP, SUSTAIN, SELECT |
| Regulatory Status | Investigational | Approved |
| CV Outcomes Data | None | SELECT positive |
Clinical Data
Cagrilintide Monotherapy (Phase 2)
| Dose | Weight Loss (26 weeks) |
|---|---|
| 1.2mg | ~6% |
| 2.4mg | ~9% |
| 4.5mg | ~11% |
Semaglutide 2.4mg (STEP 1)
| Metric | Result |
|---|---|
| Weight Loss (68 weeks) | ~15% |
| >=10% Weight Loss | 69% |
| >=15% Weight Loss | 51% |
CagriSema Combination
The combination shows additive/synergistic effects:
| Comparison | Weight Loss |
|---|---|
| CagriSema | ~15-24% (phase 2/3 data) |
| Semaglutide alone | ~15% |
| Cagrilintide alone | ~11% |
Regulatory Status
| Aspect | Cagrilintide | Semaglutide |
|---|---|---|
| FDA Status | Investigational | Approved |
| Development Path | Primarily as CagriSema combo | Multiple indications |
| Expected Timeline | CagriSema 2025-2026 | Already available |
| Standalone Pursuit | Unlikely | N/A |
Administration
| Aspect | Cagrilintide | Semaglutide |
|---|---|---|
| Route | Subcutaneous | Subcutaneous + Oral |
| Formulation | Single-agent or CagriSema | Ozempic, Wegovy, Rybelsus |
Side Effect Profile
| Effect | Cagrilintide | Semaglutide |
|---|---|---|
| Nausea | Common | Common |
| Vomiting | Common | Common |
| Constipation | Common | Less common |
| Injection Site | Reactions possible | Reactions possible |
The combination (CagriSema) has higher GI event rates than either alone, though generally manageable.
Key Differences
| Factor | Cagrilintide | Semaglutide |
|---|---|---|
| Hormone Class | Amylin | GLP-1 |
| Primary Brain Target | Area postrema | Hypothalamus |
| Insulin Effect | Indirect | Direct stimulation |
| Standalone Efficacy | Moderate | Strong |
| Strategic Value | Combination partner | Standalone or backbone |
The CagriSema Strategy
Novo Nordisk’s approach:
- Combine different satiety pathways - Amylin + GLP-1
- Maximize weight loss - Target 20%+
- Maintain tolerability - Fixed-dose combination
- Compete with tirzepatide - Match or exceed dual agonist efficacy
Summary
- Cagrilintide is an amylin analog with modest standalone efficacy but strategic value as a combination partner
- Semaglutide is the proven GLP-1 agonist with extensive data and CV benefit
- Different mechanisms allow additive effects when combined (CagriSema)
- CagriSema may offer weight loss comparable to or exceeding tirzepatide
- Cagrilintide is unlikely to be marketed as standalone therapy
This comparison is for educational purposes only. Cagrilintide is investigational. Consult a healthcare provider for treatment decisions.
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Disclaimer: This comparison is for educational purposes only and does not constitute medical advice. Individual responses to medications vary. Always consult a qualified healthcare provider before making treatment decisions.