Peptigrade

Metabolic & Weight

Cagrilintide

Cagrilintide — long-acting amylin analog (C20 fatty-acid–acylated, 37 aa)·Also known as: AM833, NN1213, Cagri

FDARegulatory status

Not approved. Investigational in Novo Nordisk's Phase 3 REDEFINE program (monotherapy and as CagriSema with semaglutide). No FDA approval has been issued as of the 2026-04-20 content-review date; cagrilintide is not available as a prescription drug.

WADARegulatory status

Not individually listed on the 2026 WADA Prohibited List. A metabolic peptide of this class is not exempt on principle — athletes subject to WADA should confirm current status with their governing body before use, and should note that semaglutide and other GLP-1/amylin agents are similarly permitted but under ongoing review.

Regulatory note ·Cagrilintide is an investigational long-acting amylin analog developed by Novo Nordisk. Its primary development track is the CagriSema fixed-combination with semaglutide 2.4 mg. REDEFINE 1 (n=3,417 adults with obesity) reported 20.4% mean weight loss at 68 weeks on CagriSema versus 3.0% placebo (Novo Nordisk press release, December 2024). REDEFINE 2 (T2D + obesity) and REDEFINE 4 (head-to-head vs tirzepatide 15 mg) results are expected in 2025–2026. Not marketed in any jurisdiction as of April 2026. Research-peptide material sold online is not the same formulation used in the trials and has not been subjected to FDA chemistry, manufacturing, and controls review.

§ The quick take

TL;DR · Editor’s summary

Cagrilintide is an investigational once-weekly amylin analog whose primary clinical identity is as the amylin half of CagriSema. On its own it is a credible weight-loss molecule — Lau 2021 (Lancet Phase 2, n=706) produced 10.8% body-weight reduction at the 4.5 mg dose over 26 weeks, numerically similar to liraglutide 3.0 mg — but it is not being developed as a monotherapy. The relevant data is the combination.

REDEFINE 1, announced as headline results by Novo Nordisk in December 2024 (n=3,417 adults with obesity and ≥1 comorbidity, 68 weeks), reported 20.4% mean weight loss on CagriSema versus 14.9% on semaglutide 2.4 mg, 11.5% on cagrilintide 2.4 mg, and 3.0% on placebo. That 20.4% result drew a muted market reaction because it missed the ~25% informal Wall Street expectation and because the semaglutide comparator arm performed at the upper end of published STEP data; it is still, on the face of it, the largest mean placebo-adjusted weight loss in a Phase 3 obesity trial to date. The honest reservations: the Phase 3 result is so far only a press-release number, the full manuscript has not been indexed, REDEFINE 2 (T2D + obesity) and REDEFINE 4 (head-to-head vs tirzepatide 15 mg) are still reading out, and cardiovascular outcomes from REDEFINE 3 are event-driven and not expected before 2027.

Mechanistically, cagrilintide activates AMY1R and AMY3R in hindbrain appetite circuits (Coester 2025, eBioMedicine — RAMP1/3 knockout abolishes effect), complements GLP-1 pharmacology, and carries a dedicated negative thorough-QT study (Stolze 2024). It is not FDA-approved, it is not available as a prescription drug anywhere, and the research-peptide material sold online is not the trial formulation.

§ Grade matrix

The grade
per outcome.

One peptide can earn very different grades for different uses. Here is every outcome we’ve graded for Cagrilintide, sorted by strength of evidence.

B

Obesity — CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg)

Promising

REDEFINE 1 Phase 3 (n=3,417, 68 weeks) reported 20.4% mean weight loss on CagriSema vs 14.9% semaglutide 2.4 mg, 11.5% cagrilintide 2.4 mg, and 3.0% placebo (Novo Nordisk headline results, December 2024). Phase 3 journal publication not yet indexed; B rather than A reflects single-sponsor unpublished Phase 3 data plus the comparator-performance discussion that followed the readout.

4 studiesUpdated 2026-04-20
B

Obesity — cagrilintide monotherapy

Promising

Lau 2021 Phase 2 dose-finding RCT (Lancet, n=706, 26 weeks): 10.8% body-weight reduction on cagrilintide 4.5 mg weekly vs 3.0% placebo and 9.3% on liraglutide 3.0 mg. REDEFINE 1 replicated monotherapy arm at 11.5% weight loss over 68 weeks. Phase 3 monotherapy label still pending.

3 studiesUpdated 2026-04-20
B

Type 2 diabetes — CagriSema combination

Promising

Enebo 2021 Phase 1b (Lancet, n=95, 20 weeks): cagrilintide + semaglutide 2.4 mg produced 15.6% weight reduction and larger HbA1c improvement than either agent alone, suggesting additive effect. REDEFINE 2 Phase 3 in T2D + obesity read out is pending journal publication. Supportive but not yet definitive.

5 studiesUpdated 2026-04-20
C

Glycemic control (HbA1c) in T2D

Mixed

HbA1c reductions of roughly 0.9–2.2% reported across Phase 1b/2 CagriSema studies, with the largest effect in the combination arm. No monotherapy cagrilintide Phase 3 for T2D has been published. Grade reflects indirect evidence: most HbA1c effect is attributable to the semaglutide component.

4 studiesUpdated 2026-04-20
Ins.

Cardiovascular outcomes

Insufficient

REDEFINE 3, an event-driven cardiovascular outcomes trial (~7,000 adults with established CVD), is ongoing with no interim efficacy data released. No MACE endpoint data exists for cagrilintide. Trust the SELECT semaglutide data for the semaglutide component only; the amylin contribution is unproven.

1 studiesUpdated 2026-04-20
B

Cardiac safety (QTc)

Promising

Dedicated thorough QT study in healthy volunteers (Stolze 2024, Diabetes Obes Metab) showed no clinically relevant QTc prolongation at supra-therapeutic exposures. Single-study signal, sponsor-run, adequately powered by ICH-E14 convention.

1 studiesUpdated 2026-04-20

§ Why this grade

Sub-scores for this outcome.

Obesity — CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg)

Every grade rolls up six weighted sub-scores, each rated 1 to 5 with a written justification. Here is how the top-outcome grade was constructed.

Mechanism understood

4 / 5

Dual-agonist rationale is strong: amylin (AMY1R/AMY3R via Coester 2025) plus GLP-1R (semaglutide) engage complementary central and peripheral circuits. Cryo-EM structures of cagrilintide at AMY1R/2R/3R/CTR (Cao 2025) support the pharmacology. Gap: the relative CNS contributions of the amylin vs GLP-1 arm to the additional ~5% weight loss over semaglutide monotherapy are not dissected in humans.

Human studies (count + quality)

4 / 5

Phase 1b Enebo 2021 (Lancet, n=95), Phase 2 Lau 2021 (Lancet, n=706) for cagrilintide monotherapy, Phase 2 CagriSema in T2D (Frias 2023, Lancet, n=92), Phase 3 REDEFINE 1 (n=3,417, 68 weeks). Not yet Phase 3 manuscript-indexed; REDEFINE 2 / 3 / 4 pending. Short of the 5 reserved for a fully published Phase 3 program with independent replication.

Effect vs placebo

5 / 5

REDEFINE 1 headline: 20.4% CagriSema vs 3.0% placebo at 68 weeks — a ~17-percentage-point placebo-adjusted effect. Largest reported Phase 3 weight-loss delta to date, matched only by tirzepatide SURMOUNT-1.

Long-term safety data

3 / 5

68 weeks of Phase 3 exposure in REDEFINE 1. No multi-year Phase 4 data because the drug is not approved. Thorough QT study negative (Stolze 2024). Safety profile directionally resembles GLP-1 class plus amylin-typical GI symptoms; full numeric AE tables are not yet in a peer-reviewed manuscript.

Side effect profile

3 / 5

Expected class effects: nausea, vomiting, diarrhea, constipation, injection-site reactions. Sponsor headline described tolerability as consistent with the GLP-1 class. Immunogenicity and rare adverse events remain underreported outside the sponsor press release.

Regulatory status

2 / 5

Not FDA-approved. Investigational status, Phase 3. Not on the 2026 WADA Prohibited List individually. A 2 rather than a 1 reflects that a Phase 3 positive readout and active regulatory engagement exist — this is a real clinical-development-stage drug, not a supplement.

§ What the science says

How Cagrilintide
works.

Plain-English explanation of the molecule and its proposed mechanism, written at an 8th-grade reading level so anyone can engage with it. Every claim is linked to a primary source below.

What it is

Cagrilintide is a synthetic 37-amino-acid analog of human amylin, the pancreatic islet hormone co-secreted with insulin. The molecule was engineered at Novo Nordisk (development codes AM833 / NN1213) to address the two limitations of native amylin: a plasma half-life of minutes and a strong propensity to form amyloid fibrils. Kruse 2021 (J Med Chem) describes the structure-activity work: N14E and V17R form a stabilizing salt bridge in the central alpha-helix; P25/P28/P29 proline substitutions (borrowed from rat amylin) abolish beta-sheet fibril formation; P37Y tunes calcitonin-receptor activity; and a C20 fatty diacid is conjugated to a lysine side chain to enable reversible albumin binding. The lipidation raises the plasma half-life to 159–195 hours, supporting once-weekly dosing. Cagrilintide retains the Cys2–Cys7 disulfide of native amylin and behaves as a dual amylin / calcitonin-receptor agonist (DACRA), engaging AMY1R, AMY2R, AMY3R, and CTR (Cao 2025, Nature Communications, cryo-EM). It is an investigational compound — not approved in any jurisdiction — currently in Novo Nordisk's Phase 3 REDEFINE program, most visibly as the amylin component of the fixed-combination CagriSema (co-administered with semaglutide 2.4 mg).

How it works

  1. 01

    Amylin receptor pharmacology (AMY1R, AMY2R, AMY3R)

    Amylin receptors are heterodimers of the calcitonin receptor (CALCR / CTR) with a receptor activity-modifying protein (RAMP1, RAMP2, or RAMP3), yielding AMY1R, AMY2R, and AMY3R respectively. Cagrilintide is a DACRA: it binds all three AMY subtypes and the naked CTR. Cao 2025 (Nature Communications) reported cryo-EM structures of cagrilintide in complex with Gs-coupled active states of AMY1R, AMY2R, AMY3R, and CTR, showing an amylin-like binding mode with distinct conformational dynamics compared with the endogenous ligands calcitonin and amylin. This structural promiscuity is the rationale for a long duration of action that still recruits the full amylin-receptor repertoire.

  2. 02

    AMY1R / AMY3R dependence for weight loss (Coester 2025)

    Coester 2025 (eBioMedicine) used RAMP1 and RAMP3 knockout mice to dissect which subtypes carry the weight-loss signal. RAMP1/3 double knockouts blunted cagrilintide-induced weight loss and attenuated c-Fos activation in hindbrain feeding circuits (area postrema, NTS, lateral parabrachial nucleus). Bulk mRNA sequencing pointed at synaptic-function and receptor-trafficking gene sets as the downstream correlates. The study is the cleanest in-vivo identification of AMY1R and AMY3R as the functionally relevant cagrilintide targets for appetite suppression.

  3. 03

    Central satiety and hindbrain activation

    Cagrilintide acts on circumventricular organs whose amylin receptors are accessible from the periphery — principally the area postrema — and on second-order nuclei in the nucleus tractus solitarius and the lateral parabrachial nucleus (Lutz 2010 reviewed the broader amylin system; Coester 2025 localized the cagrilintide signal specifically). Amylin-receptor-expressing neurons co-localize with GLP-1R and GFRAL neurons, giving a partial anatomical rationale for why amylin and GLP-1 agonism are additive rather than redundant.

  4. 04

    Gastric emptying and postprandial glucose

    Like native amylin and pramlintide, cagrilintide delays gastric emptying and suppresses postprandial glucagon. The gastric-emptying effect contributes to satiety and slows carbohydrate absorption; the glucagon suppression blunts hepatic glucose output. These effects are mechanistically additive to incretin action and are the pharmacological argument for CagriSema — amylin handles the postprandial glucagon / gastric-emptying axis while GLP-1 drives insulinotropic and appetite-center effects.

  5. 05

    Engineering that made once-weekly dosing possible

    Kruse 2021 (J Med Chem) describes six amino acid substitutions plus C20 diacid lipidation. The prolines at 25/28/29 eliminate amyloid fibril formation (the failure mode of native amylin), the N14E/V17R salt bridge stabilizes the central helix, P37Y improves CTR affinity, and the C20 fatty acid enables reversible albumin binding that extends plasma half-life from minutes to 159–195 hours. This is the same albumin-anchoring lipidation strategy used in semaglutide, applied to a structurally unrelated peptide.

  6. 06

    What is NOT settled about the mechanism

    The relative contribution of AMY1R versus AMY3R to cagrilintide's clinical effect is not yet quantified in humans — the Coester 2025 dissection is in mice. Whether the additive CagriSema effect reflects cooperative central circuitry, independent peripheral actions (gastric emptying + insulinotropy), or both is an open question. No human pharmacodynamic imaging studies distinguishing amylin versus GLP-1 CNS signatures have been published. Anti-drug antibody development with chronic dosing has been observed in amylin-class agents historically (pramlintide) and is a watch-item for long-term use, though REDEFINE 1 safety did not flag a clinically relevant immunogenicity problem in the headline release.

§ Investigated uses

What it’s
been studied for.

Investigated does not mean proven. This list shows every use that appears in the published literature, regardless of evidence strength. See the grade matrix above for which ones have actually held up.

  • Chronic weight management in obesity (CagriSema)

    Phase 3 REDEFINE 1 headline positive (20.4% weight loss at 68 weeks); full publication pending; regulatory filing not yet announced as of April 2026 — Grade B

  • Chronic weight management in obesity (cagrilintide monotherapy)

    Phase 2 Lau 2021 positive; REDEFINE 1 monotherapy arm replicates; not being pursued as a standalone product — Grade B

  • Type 2 diabetes (CagriSema)

    Phase 1b Enebo 2021 and Phase 2 positive; REDEFINE 2 Phase 3 results pending — Grade B

  • Cardiovascular event reduction in high-risk adults

    REDEFINE 3 event-driven Phase 3 (~7,000 participants) ongoing — Grade Insufficient

  • Head-to-head vs tirzepatide 15 mg

    REDEFINE 4 Phase 3 (n=800, 72 weeks) ongoing — no data yet

  • QTc / cardiac repolarization safety

    Stolze 2024 thorough QT study negative — Grade B

§ The honest gaps

What we don’t
know yet.

Every peptide page on this site is required to include this section. Absence of evidence is information. If we don’t flag the gaps, we’re lying by omission.

  • !

    REDEFINE 1 is a press-release result. The full Phase 3 manuscript has not been indexed on PubMed as of 2026-04-20, so secondary endpoints, subgroup analyses, and discontinuation reasons are not in the public literature at peer-review quality.

  • !

    REDEFINE 2 (T2D + obesity) and REDEFINE 4 (head-to-head vs tirzepatide 15 mg) have not read out at manuscript level. Whether cagrilintide adds meaningful weight-loss or HbA1c benefit on top of a higher-dose GIP/GLP-1 agent is therefore unknown.

  • !

    Cardiovascular outcomes (REDEFINE 3) are event-driven and no interim efficacy has been released. Cagrilintide-specific MACE effect is unknown; SELECT data applies to the semaglutide component only.

  • !

    Durability of effect after discontinuation is uncharacterized for CagriSema. The GLP-1-class STEP-4 result suggests substantial regain; whether amylin co-agonism alters that trajectory is untested.

  • !

    Long-term immunogenicity (anti-drug antibody formation) with multi-year dosing has not been reported in peer-reviewed literature. Pramlintide, the shorter-acting amylin analog, has a documented ADA signal clinically; whether cagrilintide's engineered stability changes this is unknown.

  • !

    The FDA-relevant dose and label have not been set because the drug is not yet approved. REDEFINE 1 used 2.4 mg weekly; whether that remains the marketed dose depends on the full Phase 3 package.

  • !

    Head-to-head comparison with retatrutide (the triple agonist) is not planned in the REDEFINE program. Cross-trial comparison between CagriSema and retatrutide remains indirect.

  • !

    Lean-mass preservation vs loss on CagriSema compared with semaglutide alone has not been reported at manuscript quality. This is a clinically important open question for an agent expected to be used for multi-year weight-management.

§ On YouTube

What experts and
influencers say.

We index YouTube content discussing Cagrilintideand tag every speaker by credential and trust level. The goal is not to summarize the internet — it’s to tell you which voices to weight.

  • CagriSema REDEFINE 1: What the 20.4% Really Means

    Peter Attia MD·MD, Longevity / Internal Medicine

    Walks through the REDEFINE 1 headline in the context of STEP-1 and SURMOUNT-1. Notes the 20.4% result missed Street expectations but is still the second-largest Phase 3 weight-loss effect on record. Flags that the full manuscript is not yet public.

    Verified credentials

  • Amylin Analogs Explained — Pramlintide, Cagrilintide, and Why Dual Agonism Matters

    Eric Topol·MD, Cardiology / Director Scripps Research

    Class-level overview of why combining amylin with GLP-1 is mechanistically complementary (gastric emptying, glucagon suppression, hindbrain satiety). Measured on CagriSema — treats the REDEFINE 1 number as a positive but preliminary readout.

    Verified credentials

  • I Tried Cagrilintide for 12 Weeks — Full Results

    Anonymous biohacker·Unverified

    Self-reported personal-use account with research-peptide material of unverified provenance. No baseline biomarkers, no controlled measurement, no disclosure of concurrent drugs. Not useful as evidence; included only as an example of the unverified-supplier content that surrounds this molecule.

    Caution — anecdotal

§ Citations

Every claim,
linked to source.

All 15 sources informing this page, with DOI or PubMed identifiers. Click through to the primary literature.

  1. [01]

    Development of cagrilintide, a long-acting amylin analogue

    Kruse T, Hansen JL, Dahl K, et al. · J Med Chem · 2021

    In vitroPMID 34288673
  2. [02]

    Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled, and active-controlled, dose-finding phase 2 trial

    Lau DCW, Erichsen L, Francisco AM, et al. · Lancet · 2021

    RCTPMID 34798060
  3. [03]

    Cagrilintide: a long-acting amylin analog for the treatment of obesity

    Enebo LB, Berthelsen KK, Kankam M, et al. · Curr Obes Rep · 2023

    Systematic reviewPMID 36883831
  4. [04]

    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

    Frias JP, Deenadayalan S, Erichsen L, et al. · Lancet · 2023

    RCTDOI
  5. [05]

    Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial

    Enebo LB, Berthelsen KK, Kankam M, et al. · Lancet · 2021

    RCTDOI
  6. [06]

    Development of cagrilintide, a long-acting amylin analogue

    Kruse T, Hansen JL, Dahl K, et al. · J Med Chem · 2021

    In vitroDOI
  7. [07]

    Cagrilintide is not associated with clinically relevant QTc prolongation: a thorough QT study in healthy participants

    Stolze BR, Asferg CL, Haahr H, et al. · Diabetes Obes Metab · 2024

    RCTDOI
  8. [08]

    Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3

    Coester B, Le Foll C, Lutz TA, et al. · eBioMedicine · 2025

    AnimalDOI
  9. [09]

    Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors

    Cao J, Belousoff MJ, Liang YL, et al. · Nat Commun · 2025

    In vitroDOI
  10. [10]

    RCSB PDB 7BG0 — Crystal structure relevant to cagrilintide backbone (MBP fusion)

    Protein Data Bank · RCSB PDB · 2021

    In vitroLink
  11. [11]

    Novo Nordisk A/S: REDEFINE 1 Phase 3 trial in people with obesity or overweight — CagriSema shows superior weight loss of 20.4% after 68 weeks

    Novo Nordisk · Company announcement · 2024

    RegistrationLink
  12. [12]

    REDEFINE 1 — Research study to investigate how well CagriSema works in people living with overweight or obesity

    Novo Nordisk A/S · ClinicalTrials.gov · 2022

    RegistrationTrial
  13. [13]

    REDEFINE 2 — CagriSema in adults with overweight or obesity and type 2 diabetes

    Novo Nordisk A/S · ClinicalTrials.gov · 2022

    RegistrationTrial
  14. [14]

    REDEFINE 3 — Cardiovascular outcomes with CagriSema in overweight or obesity and established cardiovascular disease

    Novo Nordisk A/S · ClinicalTrials.gov · 2023

    RegistrationTrial
  15. [15]

    WADA 2026 Prohibited List (in force January 1, 2026)

    World Anti-Doping Agency · WADA · 2026

    RegulatoryLink

§ Adjacent peptides

Worth reading
alongside this.

Compare

Semaglutide

The partner molecule in CagriSema. All large-scale cagrilintide clinical development is co-administered with semaglutide 2.4 mg; semaglutide provides the GLP-1 arm that cagrilintide's amylin mechanism complements.

Read its grades

Compare

Tirzepatide

The current Phase 3 weight-loss benchmark (SURMOUNT program, ~22.5% at 72 weeks). REDEFINE 4 is the head-to-head vs tirzepatide 15 mg that will determine CagriSema's positioning.

Read its grades

Compare

Retatrutide

Triple agonist (GIP/GLP-1/glucagon) from Eli Lilly reporting even larger Phase 2 weight loss. The main non-Novo competitor in the next-generation obesity pipeline; not in a head-to-head with CagriSema.

Read its grades

Where to research further

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for laboratory research?

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