Cagrilintide
An investigational amylin analogue studied alone and combined with semaglutide as CagriSema. Phase 2 complete; phase 3 REDEFINE programme reporting.
Metabolic & Weight
CagriSema
Cagrilintide and semaglutide in one weekly injection. Phase 3 trials completed with roughly 20-23% mean weight loss, below the headline figure the programme was expected to hit.
Overview
Two appetite pathways in one shot. Semaglutide acts on the GLP-1 receptor, which slows stomach emptying and signals fullness after eating. Cagrilintide mimics amylin, a second hormone released alongside insulin that reduces meal size and dampens food-seeking behaviour. Because they work through different receptors, the effects add rather than overlap, which is the whole rationale for combining them.
A fixed-ratio co-formulation of cagrilintide, a long-acting acylated amylin analogue with activity at calcitonin and amylin receptor complexes (AMY1-3), and semaglutide, an acylated GLP-1 receptor agonist. Amylin agonism reduces gastric emptying and acts on area postrema and hypothalamic circuits to reduce meal size; GLP-1 agonism acts on hindbrain and hypothalamic POMC/CART neurons and delays gastric emptying. Both components are albumin-bound via C18/C20 fatty-diacid side chains giving once-weekly kinetics. The combination produced greater weight reduction than either component alone in phase 2, with the phase 3 REDEFINE programme reporting mean weight loss in the low twenties percent.
Research areas
ObesityType 2 diabetesAppetite regulation
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| Cagrilintide 2.4 mg with semaglutide 2.4 mg once weekly, titrated over 16–20 weeksTitration exists to limit gastrointestinal adverse effects, which are dose-dependent. | REDEFINE phase 3 programme |
| Escalating combination doses up to 2.4/2.4 mg weekly over 20 weeks in phase 2Phase 2 dose-finding in type 2 diabetes. | Frias et al., The Lancet 2023 |
Trial status
Phase 3 REDEFINE programme completed in obesity and in type 2 diabetes. Phase 2 results published in The Lancet.
Reported safety signals
- Nausea, vomiting, constipation and diarrhoea are the dominant adverse effects, as with all incretin-based therapy.
- Carries the same rodent thyroid C-cell tumour signal and contraindication in medullary thyroid carcinoma or MEN2 as other GLP-1 agonists.
- Combination therapy raises the rate of gastrointestinal adverse events relative to semaglutide alone.
- Compounded or research-sourced "CagriSema" is not the trial formulation and its ratio and content are unverified.
Common questions
Is CagriSema better than tirzepatide?
No head-to-head trial has been published. CagriSema reported mean weight loss in the low twenties percent in phase 3, broadly in the same range as tirzepatide at its highest dose, but comparing across separate trials with different populations and durations is not a valid substitute for a direct comparison.
Primary sources
- 01
Efficacy 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 trial
- 02
REDEFINE 1: cagrilintide/semaglutide in adults with overweight or obesity
- 03
Amylin analogues in the treatment of obesity
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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