CagriSema
CagriSema (Cagrilintide + Semaglutide)
The amylin + GLP-1 combo
An investigational fixed-dose combination of cagrilintide (a long-acting amylin analog) and semaglutide (a GLP-1 agonist) from Novo Nordisk. The amylin arm restores leptin sensitivity while the GLP-1 arm handles appetite and glucose — a different pairing from the GIP-based dual agonists. In the REDEFINE Phase 3 programme it reached ~20.4% body-weight loss (ITT), short of its 25% target. NDA filed; under review in 2026, not yet approved.
Key Benefits
~20.4% body-weight loss in REDEFINE Phase 3 (ITT)
Dual amylin + GLP-1 mechanism, distinct from the GIP-based duals
Amylin arm restores leptin sensitivity — relevant to high-set-point genetics
GLP-1 arm covers the glycemic / beta-cell side
Once-weekly subcutaneous dosing
Mechanism of Action
How CagriSema works
CagriSema combines two appetite hormones that work on different systems:
- Amylin agonism (cagrilintide) — activates amylin receptors in the hindbrain to slow gastric emptying and signal satiety, and — uniquely — helps restore leptin sensitivity, the signal that's blunted in people with a high genetic set-point
- GLP-1 agonism (semaglutide) — central appetite suppression plus glucose-dependent insulin secretion, the same axis as Ozempic/Wegovy
- Leptin re-sensitization — the amylin component is the differentiator: where pure GLP-1 drugs can under-serve a leptin-resistant, high-set-point patient, the amylin arm targets that resistance directly
- Not CYP-metabolized — both peptides are cleared by proteolysis, so liver-enzyme genetics don't apply; response is set by receptor and appetite-pathway genes
Your Genetics & CagriSema
Genetic variants that affect your response
These SNPs determine how effectively CagriSema works for you specifically. A genetic peptide report identifies your variants before you start.
The Gln223Arg variant impairs leptin-receptor signaling, blunting the 'I'm full' signal. CagriSema's amylin arm helps restore leptin sensitivity, so carriers of the impairing allele are mechanistically the people a pure GLP-1 most under-serves — and where the combo earns its place.
FTO risk alleles raise the body's defended weight set-point and appetite drive. A higher set-point is exactly the case where adding the amylin/leptin arm to GLP-1 is most justified.
The strongest common type 2 diabetes variant. T-allele carriers have blunted insulin secretion that the semaglutide component of CagriSema can partly compensate for.
Affects the efficiency of the GLP-1 arm. Weak-signaling variants shift more of the benefit onto the amylin component.
Which variants do you carry?
Upload your DNA data or order a kit to find out.
Evidence & Research
15+
Published studies
Animal studies and in vitro data with promising but limited clinical validation
Common Stacks
CagriSema is commonly combined with:
Frequently Asked Questions
What is CagriSema used for?
CagriSema is an investigational weight-management combination of cagrilintide (amylin) and semaglutide (GLP-1). It's designed for people who need more than a GLP-1 alone — particularly those with leptin resistance and a high genetic set-point, where the added amylin arm helps restore satiety signaling.
Does genetics affect CagriSema response?
Yes — and in a specific way. LEPR (leptin receptor) and FTO (set-point) variants are what make the amylin arm worth adding; if your genetics point to leptin resistance and a high set-point, CagriSema's combo is more justified than a GLP-1 alone. TCF7L2 and GLP1R shape the semaglutide side.
Is CagriSema approved?
Not yet. As of 2026 CagriSema is investigational — an NDA has been filed under the REDEFINE programme and it's under review. Its Phase 3 result (~20.4% ITT) came in below its 25% target, which is part of the ongoing regulatory picture. It is not an available prescription.
Learn More About CagriSema
genetics
Semaglutide vs Tirzepatide: Which Actually Works Better Based on Your GLP-1 Receptor Gene?
11 min read
peptide guides
Best Peptides for Weight Loss: A DNA-Guided Ranking (2026)
14 min read
peptide guides
Why Retatrutide Outperforms Ozempic and Mounjaro in Weight Loss (And Why It Isn't Approved Yet)
13 min read
Your next move
Two ways forward with CagriSema.
Not sure it's for you?
Will CagriSema work for your genes — and at what dose?
Your report scores CagriSema against your receptor, CYP and pathway variants — likely responder, non-responder, and a sensible starting dose — in minutes.
Analyze my DNA — $99