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CagriSema is a fixed combination of cagrilintide (amylin analog) and semaglutide (GLP-1RA) studied in Phase 3 REDEFINE trials — 22.7% mean body weight reduction at 68 weeks, exceeding semaglutide-alone benchmarks.
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How it works
CagriSema activates two pharmacologically independent receptor systems: semaglutide engages GLP-1 receptors (satiety, gastric emptying, insulin secretion) and cagrilintide engages amylin receptors (area postrema/NTS satiety signaling, glucagon suppression, gastric motility). The mechanistic independence produces additive weight reduction beyond either receptor alone — confirmed in REDEFINE-1 Phase 3 data.
Compound profile
Product definition
CagriSema is a fixed combination of cagrilintide (amylin analog) and semaglutide (GLP-1RA) studied in Phase 3 REDEFINE trials — 22.7% mean body weight reduction at 68 weeks, exceeding semaglutide-alone benchmarks.
CagriSema is Novo Nordisk's investigational fixed-ratio combination product containing cagrilintide 2.4 mg and semaglutide 2.4 mg in a single weekly subcutaneous injection. It is designed for the obesity indication, with the REDEFINE Phase 3 program (REDEFINE-1, -2, -3) constituting the pivotal trial package. The pharmacological architecture exploits receptor system independence: GLP-1R and amylin receptor populations have distinct anatomical distributions, distinct signal transduction pathways (GLP-1R via cAMP/PKA/Epac; amylin receptor via cAMP + CGRP-related pathways), and distinct downstream physiological effects. Combining them is pharmacologically analogous to combining two independently validated mechanisms rather than compounding redundant effects at the same receptor. Retatrutide's Phase 2 results (24.2% at 48 weeks) and CagriSema's Phase 3 results (22.7% at 68 weeks) currently represent the frontier of pharmacological weight reduction — both operating through multi-receptor strategies that exceed the ceiling of single-pathway GLP-1R activation.
Research audience
CagriSema is used by researchers in combination incretin pharmacology, neuroendocrine satiety signaling, amylin receptor biology, obesity mechanisms, and multi-receptor metabolic research. It is relevant for any protocol studying how independent satiety pathways interact or stack when activated simultaneously.
Research context
The REDEFINE program was launched on the basis of pramlintide-semaglutide combination Phase 2 data from Dan Drucker's group and Novo Nordisk investigators, which showed that short-acting amylin + GLP-1RA combination produced additive weight reduction in Phase 2. Cagrilintide replaced pramlintide in the program as the long-acting component, enabling once-weekly fixed-ratio dosing. The mechanistic research question REDEFINE answers is fundamental to obesity pharmacology: does stacking independent satiety pathway activation produce additive outcomes? The answer from REDEFINE-1 appears to be yes — approximately 7–8 additional percentage points of body weight reduction versus semaglutide alone suggests substantial amylin pathway contribution. For preclinical research contexts, the CagriSema compound pair provides a model system for studying how hypothalamic and brainstem satiety circuits interact when both GLP-1R and amylin receptor pathways are activated simultaneously, as well as the relative contribution of glucagon suppression versus direct satiety signaling to the amylin component's weight effects.
Common questions
You might also want to check out these products.
Cagrilintide
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Cagrilintide is a long-acting amylin analog (~7-day half-life) developed for once-weekly combination dosing with semaglutide — the most clinically advanced amylin compound, with Phase 3 REDEFINE data published.
Semaglutide
$16.00
Semaglutide is a GLP-1 receptor agonist with ~7-day half-life via albumin-binding fatty acid modification — the most extensively studied GLP-1RA, anchoring the SUSTAIN and STEP clinical programs.
Retatrutide
$30.00
Retatrutide is a once-weekly triple GLP-1/GIP/glucagon receptor agonist — Phase 2 data showed 24.2% mean body weight reduction at 48 weeks, the highest result in obesity pharmacology Phase 2 trial history at publication.
Tirzepatide
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Tirzepatide is a dual GIP/GLP-1 receptor agonist — the first of its class, with Phase III data showing 22.5% mean body weight reduction at 72 weeks, the highest performance in obesity pharmacology trial history at publication.
Research Use Only
Sold for laboratory and research purposes only. Not approved for, nor intended for, human or veterinary consumption, diagnostic use, or therapeutic application. These products have not been evaluated by the Food and Drug Administration. Keep out of reach of children. For use by qualified researchers only.
Nothing on this page constitutes medical advice, a treatment recommendation, or a clinical protocol. Consult a qualified healthcare provider before making any health or treatment decisions.
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