Cagrilintide

Research Reagent · Laboratory Use Only

What does clinical research show about cagrilintide's mechanism and efficacy when combined with semaglutide?

Cagrilintide is a long-acting amylin analogue that activates amylin receptor subtypes AMY1R, AMY2R, and AMY3R in central satiety pathways. In the Phase 3 REDEFINE 1 trial published in the New England Journal of Medicine (2025–2026), once-weekly cagrilintide 2.4 mg co-administered with semaglutide 2.4 mg (CagriSema) produced 20.4% mean body weight reduction at 68 weeks in adults with obesity, with 60% achieving ≥20% weight loss. A New Drug Application was submitted to the FDA in December 2025.

Scientific AbstractPMID 40544432 · 2026

Background

Cagrilintide is a long-acting amylin analogue that, when combined with semaglutide as CagriSema, addresses complementary satiety pathways. REDEFINE 1 is a Phase 3 randomised, double-blind, placebo-controlled trial evaluating once-weekly cagrilintide 2.4 mg + semaglutide 2.4 mg in adults with overweight or obesity without type 2 diabetes.

Results

At 68 weeks, CagriSema produced a mean body weight reduction of 20.4% versus 3.0% with placebo. 60% of participants achieved ≥20% weight loss and 23% lost ≥30%. 88% of participants with prediabetes returned to normoglycemia. Gastrointestinal adverse events occurred in 79.6% of the CagriSema group (vs 39.9% placebo), predominantly mild-to-moderate and transient. Novo Nordisk submitted a New Drug Application for CagriSema in December 2025; regulatory decision expected late 2026.

Mechanistic Research SummaryCurated from PubMed

This data is for laboratory research purposes only. Not for human or animal consumption.

What is Cagrilintide?

Cagrilintide is a long-acting synthetic amylin analogue developed by Novo Nordisk. Amylin is a peptide co-secreted with insulin from pancreatic beta cells that regulates satiety through central amylin receptors. Cagrilintide is the amylin component of the combination drug CagriSema (cagrilintide + semaglutide), which is under FDA regulatory review as of 2026.

Mechanism of Action

Cagrilintide binds to amylin receptor subtypes AMY1R, AMY2R, and AMY3R — heteromeric complexes of the calcitonin receptor (CTR) and receptor activity-modifying proteins (RAMPs 1–3). Receptor activation engages both homeostatic (hypothalamic) and hedonic (mesolimbic) satiety pathways to reduce food intake. Structurally, cagrilintide contains 14E/17R mutations to stabilize the central helix via a salt bridge; 25P/28P/29P mutations (as in rat amylin) to prevent fibril formation; a C-terminal proline for enhanced CTR potency; and an N-terminally linked C20 fatty acid for extended half-life (~159–195 hours), enabling once-weekly dosing. When combined with semaglutide (GLP-1R agonist), the complementary amylin and incretin pathways produce synergistic weight reduction.

Observed Laboratory Results

  • Phase 3 REDEFINE 1: CagriSema produced 20.4% mean body weight reduction at 68 weeks versus 3.0% with placebo in adults with obesity without type 2 diabetes.
  • ≥20% weight loss: Achieved by 60% of CagriSema-treated participants; ≥30% achieved by 23%.
  • Prediabetes reversal: 88% of participants with prediabetes returned to normoglycemia in the CagriSema arm.
  • Phase 3 REDEFINE 2 (type 2 diabetes): 15.7% weight loss with significantly improved HbA1c versus comparators.
  • Phase 2 dose-escalation: Cagrilintide monotherapy demonstrated dose-dependent weight reduction; combined with semaglutide 2.4 mg, weight loss reached 17.1% versus 9.8% for semaglutide monotherapy at week 20.
Clinical Research Parameters
2 trials4 human studies

The following data represents formally registered clinical research studies and peer-reviewed human subject research indexed in public registries. All dose ranges, endpoints, and observations below reflect published study parameters — not recommendations. For research reference only.

ClinicalTrials.gov ↗
NCT05567796
COMPLETEDPhase IIIn=3,417

A Research Study to See How Well Cagrilintide and Semaglutide Together Help Adults With Overweight or Obesity Lose Weight (REDEFINE 1)

REDEFINE 1 is a Phase 3a randomised, double-blind, placebo-controlled trial evaluating once-weekly CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg) versus placebo in adults with overweight or obesity without type 2 diabetes. At 68 weeks, CagriSema produced a mean body weight reduction of 20.4% versus 3.0% with placebo. 60% of participants achieved ≥20% weight loss; 23% achieved ≥30% weight loss. 88% of participants with prediabetes returned to normoglycemia. Results published in NEJM (2025) and formed the basis for a New Drug Application submitted to the FDA in December 2025.

Study Interventions
Cagrilintide + Semaglutide (CagriSema), Placebo
Primary Endpoints
Percent change in body weight from baseline to week 68; Proportion of participants achieving ≥5% body weight reduction
Study Period
2022-10 → 2024-12
NCT06131437
COMPLETEDPhase IIIn=1,000

A Research Study to Compare How Well CagriSema and Tirzepatide Help Adults With Overweight or Obesity Lose Weight (REDEFINE 4)

REDEFINE 4 is an open-label Phase 3 trial comparing CagriSema (cagrilintide + semaglutide) head-to-head against tirzepatide in adults with obesity. CagriSema achieved 23% weight loss. The trial did not meet the non-inferiority threshold versus tirzepatide.

Study Interventions
Cagrilintide + Semaglutide (CagriSema), Tirzepatide
Primary Endpoints
Percent change in body weight from baseline
Study Period
2023-11 → 2025-09

All data presented on this page is for laboratory research purposes only. Cagrilintide is referenced here as a research reagent. This page does not constitute medical advice, clinical guidance, or endorsement of any compound for human or animal use. All referenced studies are available via PubMed (PMID: 40544432) and the DOI-linked journal publication. Researchers must consult applicable institutional and regulatory frameworks before conducting any protocols.