COMPOUND

Compounds / GLP-1 agonists

CagriSema

CagriSema (cagrilintide 2.4mg + semaglutide 2.4mg fixed-dose combination)

GLP-1 agonists SubQ Investigational

Investigational once-weekly fixed-dose combination of cagrilintide (amylin analog) and semaglutide (GLP-1 RA): first multi-receptor obesity drug combining a non-incretin satiety mechanism with GLP-1 agonism. REDEFINE-1 phase 3: -20.4% weight loss at 68 weeks. NDA filed late 2025; PDUFA expected H2 2026. Originally trialed against an ambitious 25% weight loss target which it narrowly missed (significantly more patients achieved ≥20% loss vs placebo but mean fell short of the 25% bar). Novo stock fell ~20% on the readout but the FDA application proceeded.

At a glance

Half-life
~7 days Both components ~7 day t½ (sema 168h, cagri 159-195h). Aligned for once-weekly dosing. Sema bioavailability ~89% SC; cagri not publicly reported.
Routes
SubQ
Evidence base
2 studies 2 human

Mechanism

Combination of two distinct mechanisms in a single weekly SC injection. Semaglutide (GLP-1 RA): glucose-dependent insulin secretion, glucagon suppression, gastric emptying delay, hypothalamic appetite suppression. Cagrilintide (amylin analog): hindbrain area postrema satiety, additional gastric emptying delay (independent mechanism), enhanced postprandial satiety. Two satiety mechanisms acting on different brain circuits + dual gastric emptying mechanisms + dual postprandial signaling. REDEFINE 1: -20.4% weight loss vs -3.0% placebo at 68 weeks in adults with obesity; REDEFINE 2: -13.7% vs -3.4% in T2D patients, with 73.5% reaching HbA1c ≤6.5%. Designed to overcome semaglutide weight loss plateau.

Dosing

Any amounts shown here are reported from published studies only. 2 of 2 catalogued studies involved human subjects. COMPOUND does not publish its own dosing guidance.

Where a study reports an amount, it appears in that study's entry below, attributed to the source.

Published evidence

  1. Human RCT 2025

    Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)

    Garvey WT, Blüher M, Osorto CK, et al. NEJM

    Phase 3a, n=3,417, 68 weeks: CagriSema -20.4% vs placebo -3.0% (p<0.001). Significantly more participants achieved ≥20%, ≥25%, and ≥30% weight loss vs placebo (exact thresholds in supplementary data). Separate monotherapy arms in trial: semaglutide 2.4mg ~-14.9%, cagrilintide 2.4mg ~-11.5%.

    PMID 40544432

  2. Human RCT 2025

    Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2)

    Davies M, Pieber TR, Hartoft-Nielsen ML, et al. NEJM

    Phase 3a, n=1,206, 68 weeks: CagriSema -13.7% vs placebo -3.4% (T2D cohort). 73.5% reached HbA1c ≤6.5% vs 15.9% placebo.

    PMID 40544433

Reported side effects

Nausea
Very common Moderate · REDEFINE-1: 79.6% of CagriSema pts had GI AEs vs 39.9% placebo. Mostly mild-mod, transient, escalation-related.
Vomiting
Common Moderate · Higher rate than semaglutide alone.
Diarrhea
Common Mild · Class effect.
Constipation
Common Mild · Amylin component contributes; longer duration than diarrhea.
Decreased appetite
Very common Mild · Wanted effect.
Injection site reactions
Common Mild · Pruritus, erythema, induration. Higher than sema alone (cagrilintide adds reactivity).
Hypoglycemia (T2D w/ insulin/SU)
Common Serious · REDEFINE-2: T2D patients on insulin/SU showed hypoglycemia.
Discontinuation due to AE
Common Moderate · ~7% in REDEFINE-1, comparable to semaglutide monotherapy.
Pancreatitis
Rare Serious · Class warning.
Thyroid C-cell tumors
Rare Serious · BOXED WARNING expected at approval (semaglutide component).

Interactions

  • Oral medications (general) Absorption interference

    Combined GLP-1 + amylin gastric emptying delay, likely greater than either alone. Oral medication absorption may be more affected.

  • Insulin or sulfonylurea Synergy

    GLP-1 incretin + amylin satiety + insulin/SU = additive hypoglycemia. High hypoglycemia risk in T2D patients.

  • Semaglutide (SC) Redundant

    CagriSema contains semaglutide. Taken alongside another semaglutide-containing product it produces additive semaglutide exposure.

  • Tirzepatide Redundant

    Overlapping GLP-1 agonism. Concurrent GLP-1 RA use not recommended.

Reconstitution and storage

N/A pre-approval. Single SC pen expected.

N/A pre-approval; expect refrigerated unused, room temp in-use (sema standard).

Open the reconstitution calculator for CagriSema