CagriSema

Cagrilintide 2.4 mg + Semaglutide 2.4 mg · Fixed-Dose Combination · Novo Nordisk

"Novo Nordisk's answer to retatrutide — co-formulated cagrilintide (long-acting amylin analogue) plus semaglutide 2.4mg in a single weekly injection. The REDEFINE Phase 3 programme has completed. Where tirzepatide added GIP to GLP-1, CagriSema adds amylin — a different complementary mechanism with its own additive weight loss data."

Components

Cagrilintide 2.4 mg + Semaglutide 2.4 mg weekly

Phase 3 (REDEFINE 1)

~22–23% weight loss · 68 weeks

Status

UK: would be prescription only medicine once approved (POM) · WADA: not specifically listed · US FDA: NDA submission · MHRA: not yet licensed · REDEFINE Phase III complete

vs Semaglutide alone

~7% additional weight loss vs Wegovy

Protocol summary

Clinical status

Phase III complete · NDA filed

Trial dose

2.4 mg / 2.4 mg weekly SubQ

Availability

Not commercially available yet

Trial-stage

Cagrilintide 2.4 mg + Semaglutide 2.4 mg weekly SubQ (REDEFINE Phase 3 protocol)

Not commercially available yet · regulatory approval pending

How we read the evidence

Phase 3 complete · NEJM-published · NDA filed with FDA · not commercially available

Animal evidence

Standard preclinical pathway combining established science of two compounds: semaglutide (GLP-1 agonist with proven obesity outcomes) and cagrilintide (long-acting amylin analog, Phase 1/2 weight loss data). The mechanism stack — appetite regulation via GLP-1 + satiety via amylin — was validated in animal models before human trials.

Community & clinical practice

None. CagriSema is not commercially available. Anyone selling this as a research compound is selling either an unverified product, a counterfeit, or DIY-mixing semaglutide with cagrilintide (which is itself not commercially available). There is no legitimate community access; protocols matching the trial dosing exist only inside the trials.

Human trial data

Strong. Two Phase 3 trials published in NEJM (June 2025): REDEFINE 1 enrolled 3,417 adults without diabetes; REDEFINE 2 enrolled 1,206 adults with type 2 diabetes — both 68 weeks. REDEFINE 1 results: 20.4% mean weight loss with CagriSema vs 14.9% semaglutide alone, 11.5% cagrilintide alone, 3% placebo. With full adherence, weight loss reached 22.7%, with 60% of participants achieving ≥20% loss and 23% achieving ≥30%. 88% of participants with prediabetes returned to normoglycemia. The 2.4mg/2.4mg weekly dose did not hit the 25% target some analysts had projected, but the data clearly supports approval.

Regulatory status

Investigational. NDA filed with FDA (2026) for chronic weight management. Not approved by FDA, EMA, or MHRA. Pep IQ does not endorse use outside of approved clinical trials.

Convergence

CagriSema produced the highest mean weight loss seen in any large-scale obesity Phase 3 to date — 20.4% over 68 weeks, with majority of patients achieving ≥20% loss. Approval likely. But until FDA/EMA approval, this is not a community-use compound. The well-evidenced GLP-1s already approved (semaglutide, tirzepatide) cover most of the same mechanism with established access. Pep IQ's stance: wait for approval, do not source CagriSema as a research compound.

What It Is

Amylin + GLP-1 — two drugs doing what amycretin does in one

CagriSema is a fixed-dose co-formulation of cagrilintide (a long-acting amylin receptor agonist developed by Novo Nordisk) and semaglutide 2.4mg (the GLP-1 receptor agonist behind Wegovy). Both components are administered as a single weekly subcutaneous injection from a co-formulated pen. The rationale: amylin and GLP-1 work through complementary but distinct mechanisms — together producing greater weight loss than either alone.

Cagrilintide is a modified amylin analogue with fatty acid side chains that extend its half-life to enable weekly dosing — engineered the same way semaglutide was engineered from GLP-1. Amylin is co-secreted with insulin from pancreatic beta cells; it reduces postprandial glucagon, slows gastric emptying through separate pathways from GLP-1, and produces satiety through distinct neural circuits. The combination exploits both pathways simultaneously.

The key comparison: CagriSema does with two co-administered drugs what amycretin aims to do with one molecule. Both combinations target GLP-1 and amylin receptors. CagriSema is more advanced in development (Phase 3 complete); amycretin is cleaner conceptually (single molecule, potentially better pharmacokinetics) but earlier stage.

Phase 1

Safety

✅ Complete

Phase 2

Efficacy

✅ ~15–17% loss

Phase 3

REDEFINE

✅ ~22–23% loss

NDA

Submission

🔄 Anticipated

Mechanism — Why Amylin Adds to GLP-1

Complementary satiety — different circuits, additive effect

How the Two Components Work Together

Semaglutide (GLP-1R): Hypothalamic appetite suppression, glucose-dependent insulin secretion, gastric emptying delay via GLP-1R. The proven mechanism behind 15% weight loss in STEP 1. Acts primarily on central neural circuits and pancreatic beta cells.

Cagrilintide (amylin/calcitonin receptors): Amylin receptors in the area postrema and nucleus tractus solitarius (brainstem satiety centres) — distinct from hypothalamic GLP-1 receptor circuits. Reduces postprandial glucagon. Delays gastric emptying through vagal pathways separate from GLP-1's mechanism. These non-overlapping neural circuits are why the combination produces additive weight loss.

Additive effect in Phase 2: Cagrilintide alone produced approximately 10% weight loss. Semaglutide alone produced approximately 15%. CagriSema produced approximately 17–20% — greater than either alone but not fully additive. The non-full-additivity suggests some pathway overlap or compensation, but the net effect is meaningfully superior to GLP-1 monotherapy.

REDEFINE Phase 3 data: the REDEFINE 1 trial (obesity without diabetes) reported approximately 22–23% weight loss over 68 weeks — placing CagriSema between tirzepatide (~20%) and retatrutide (~28.7%) in efficacy. The comparison to semaglutide 2.4mg (Wegovy) is approximately 7 percentage points of additional weight loss from adding cagrilintide. Whether that additive benefit justifies the additional compound and formulation complexity will be a pricing and access question as much as a clinical one. REDEFINE 2 (T2D) and cardiovascular outcomes data are expected.

Benefits & Evidence

What the data shows

⚖️

Weight loss — 22–23% at 68 weeks

REDEFINE Phase 3: approximately 22–23% weight loss over 68 weeks in adults with obesity. ~7 percentage points greater than semaglutide 2.4mg alone. Additive effect of amylin component confirmed across Phase 2 and 3.

● Strong — Phase 3 RCT data

🩸

Glycaemic control

Phase 2 T2D data shows HbA1c improvements consistent with and beyond semaglutide alone. Phase 3 T2D REDEFINE 2 results pending.