Name: Cagri/Sema
Brand: Peptific
SKU: CAGRI-SEMA-5-MG
Price: 2700 USD
Availability: InStock

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.

GLP-1 Peptides

Cagri/Sema

CagriSema is Novo Nordisk's fixed-combination formulation of cagrilintide (a long-acting amylin analog) and semaglutide (GLP-1 receptor agonist), developed specifically for the REDEFINE Phase 3 obesity program. The combination's pharmacological rationale is mechanistic complementarity: the two agents activate completely distinct receptor systems with different anatomical distributions and non-overlapping downstream signaling profiles. GLP-1 receptor agonists reduce appetite and food intake primarily via gastric emptying delay and hypothalamic satiety signaling through GLP-1Rs in the arcuate nucleus and area postrema. Amylin receptor activation (via RAMP1/2/3 + calcitonin receptor complexes) produces additional satiety signals, glucagon suppression, and slowed gastric motility through receptor populations concentrated in the area postrema and nucleus tractus solitarius — structures distinct from the primary GLP-1R distribution. These are parallel satiety circuits, not redundant ones. REDEFINE-1 Phase 3 data (N=3,415, 68 weeks) published the result: 22.7% mean body weight reduction for CagriSema versus 8.0% placebo. This significantly exceeded the STEP-1 semaglutide alone benchmark of 14.9%, suggesting approximately 7–8 additional percentage points attributable to the amylin receptor pathway alongside GLP-1R activation. For researchers studying combination receptor pharmacology, independent satiety pathway stacking, or the mechanistic architecture of dual-system weight reduction, CagriSema is the defining research compound for amylin-plus-GLP-1 biology. This listing is for laboratory and preclinical research purposes only. Not for human or veterinary use.

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Product definition

What is Cagri/Sema?

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 context

How is Cagri/Sema described in the research literature?

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

Key facts about Cagri/Sema

Components: Cagrilintide (amylin analog) + Semaglutide (GLP-1RA)
Phase 3 result: 22.7% mean body weight reduction at 68 weeks (REDEFINE-1)
Developer: Novo Nordisk
Dosing: Fixed ratio, once-weekly subcutaneous
Half-life: ~7 days (both components via fatty acid modification)
Clinical status: Phase 3 REDEFINE program complete (NDA filing anticipated)
Research category: Combination incretin + amylin pharmacology, obesity, satiety neuroscience
Storage: Lyophilized components: −20°C. Reconstituted: 2–8°C, use within 30 days

Research areas

What research areas is Cagri/Sema associated with?

REDEFINE-1 Phase 3: 22.7% mean body weight reduction at 68 weeks — exceeds semaglutide-alone STEP-1 benchmark by ~8 percentage points
Two pharmacologically independent receptor systems: GLP-1R + amylin receptor (not redundant mechanisms)
Fixed-ratio single-injection weekly convenience for combination protocol research
Cagrilintide component adds glucagon suppression and area postrema/NTS satiety signaling not present in GLP-1RA alone
Amylin pathway research reference: largest Phase 3 dataset for amylin + GLP-1RA combination in literature
Mechanistically distinct from tirzepatide (GIP/GLP-1) and retatrutide (GLP-1/GIP/glucagon) — different receptor combination profile

Research audience

Who researches Cagri/Sema?

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.

Preclinical research overview

What does the preclinical literature say about Cagri/Sema?

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

Frequently asked about Cagri/Sema

How is CagriSema different from tirzepatide pharmacologically?

CagriSema combines a GLP-1RA (semaglutide) with an amylin analog (cagrilintide). Tirzepatide is a dual GLP-1/GIP receptor agonist. The receptor systems are entirely different: CagriSema adds the amylin pathway (calcitonin receptor + RAMP complexes, concentrated in brainstem); tirzepatide adds the GIP pathway (adipose tissue, pancreas, bone). Neither is definitively superior — they address different mechanistic questions about satiety biology.

Has CagriSema been submitted for regulatory approval?

As of the time of this writing, REDEFINE Phase 3 data is complete and an NDA filing is anticipated. The compound is available as a research reference for investigators studying combination amylin+GLP-1 pharmacology before commercial availability of the approved product.

Can CagriSema components be studied separately for mechanistic research?

Yes — cagrilintide and semaglutide are available separately. Studying each compound individually alongside the combination allows researchers to attribute observed effects to the amylin pathway versus the GLP-1R pathway — the standard mechanistic dissection approach for combination pharmacology research.