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CagriSema

Cagrilintide + Semaglutide Fixed-Dose Combination

An investigational fixed-dose combination of cagrilintide and semaglutide from Novo Nordisk. It targets GLP-1 and amylin pathways and is under FDA review for weight management.

Reviewed May 16, 2026·12 min read·8 citations·NDA filedGLP-1 + amylin
On this page

At a glance

CagriSema is Novo Nordisk's investigational fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg. It is technically a combination product, not a single peptide, but it belongs in the metabolic peptide evidence universe because it pairs GLP-1 biology with amylin biology in one once-weekly injection. It is not FDA-approved; Novo Nordisk filed the US NDA in December 2025.

Animal studiesModerateMechanistic support

The individual components have strong mechanistic rationale, but CagriSema itself is primarily supported by human clinical trials rather than a large independent animal literature.

Human evidenceStrong4,700+ participants

Two published Phase 3 REDEFINE trials plus earlier Phase 1b and Phase 2 studies show clinically meaningful weight and glycemic effects. FDA review is still pending.

Safety dataModeratePhase 1-3 exposure

Safety is mostly gastrointestinal and broadly consistent with GLP-1/amylin pharmacology. Longer-term, post-marketing, and rare-event data are not available because the product is not approved.

How are these scores calculated?

CagriSema's strongest signal is simple: adding amylin agonism to semaglutide produced more weight loss than either component alone in REDEFINE 1. The caution is equally simple: NDA filing is not approval, and the full real-world safety picture does not exist yet.

New research, delivered clearly

When new studies publish or clinical trials report results, we'll break them down in plain language.

Quick facts

Components
Cagrilintide 2.4 mg + semaglutide 2.4 mg
Route
Once-weekly subcutaneous injection
Developer
Novo Nordisk
FDA status
NDA filed; not approved
Main program
REDEFINE / REIMAGINE
Mechanism
GLP-1 receptor + amylin receptor pathways

Amino acid sequence

Fixed-dose combination product: cagrilintide + semaglutide

What is CagriSema?

CagriSema is a once-weekly injectable combination being developed by Novo Nordisk for weight management and type 2 diabetes. The two active components are semaglutide, the GLP-1 receptor agonist used in Wegovy and Ozempic, and cagrilintide, a long-acting amylin analogue.[5]

That makes CagriSema different from drugs such as tirzepatide or retatrutide. Tirzepatide and retatrutide are single molecules that hit multiple incretin receptors. CagriSema is a fixed-dose product combining two separate peptide drugs in one injection.

The reason it matters is the amylin pathway. GLP-1 drugs already reduce appetite, slow gastric emptying, and improve glucose handling. Amylin adds a complementary satiety signal, and REDEFINE 1 directly tested whether the combination outperformed each component alone.[1]

Regulatory status: CagriSema is under FDA review for weight management after a December 2025 NDA filing. It is not an approved prescription medicine yet. Any commercial sale before approval should be treated as unapproved.

How it works

CagriSema tries to cover two appetite-regulation channels at once:

  • Semaglutide: activates GLP-1 receptors, increasing glucose-dependent insulin secretion, reducing glucagon, slowing gastric emptying, and reducing appetite.
  • Cagrilintide: mimics amylin, a pancreatic hormone co-secreted with insulin that promotes satiety and helps regulate post-meal glucagon.

In plain terms, CagriSema is built around the idea that GLP-1 and amylin send overlapping but not identical "stop eating" signals. The clinical question was whether the combination would do more than either signal alone. REDEFINE 1 supports that additive idea in adults without diabetes; REDEFINE 2 supports it in adults with type 2 diabetes and overweight or obesity.[1][2]

How CagriSema differs from amycretin

CagriSema and amycretin both sit in the GLP-1 + amylin trend, but they are not the same design.

  • CagriSema: two separate molecules, cagrilintide and semaglutide, co-formulated or co-administered as a fixed-dose treatment.
  • Amycretin / zenagamtide: one unimolecular drug designed to activate both GLP-1 and amylin receptor pathways.

This distinction matters for dosing, manufacturing, pharmacokinetics, and regulatory review. CagriSema is closer to market because it has completed pivotal Phase 3 obesity trials and has an FDA NDA filed. Amycretin has striking early data but still needs pivotal Phase 3 confirmation.

What the research says

CagriSema is the cleanest clinical proof so far that amylin agonism can add meaningful weight loss on top of GLP-1 therapy. The evidence is strong for weight loss, but still pre-approval and pre-real-world.

Peptide Garden evidence assessment, May 2026

Research timeline

  1. 2021Human study

    Phase 1b combination study

    Cagrilintide was co-administered with semaglutide 2.4 mg in a randomized Phase 1b study, establishing early safety, PK, and pharmacodynamic context.

  2. 2023Human study

    Phase 2 type 2 diabetes data

    A small active-controlled Phase 2 trial in T2D showed the combination produced greater weight and glycemic effects than either component alone.

  3. 2025Human study

    REDEFINE 1 and REDEFINE 2 published

    Two Phase 3a trials were published in the New England Journal of Medicine, establishing the pivotal obesity and T2D evidence base.

  4. 2025Regulatory

    FDA NDA filed

    Novo Nordisk submitted a US NDA for CagriSema for chronic weight management in December 2025.

  5. 2026Human study

    REIMAGINE diabetes readouts continue

    Novo reported additional Phase 3 diabetes results and said it would discuss the T2D regulatory path with authorities.

Key clinical trials

2025·Phase 3a, double-blind, randomized, placebo- and active-controlled·n=3417High quality

REDEFINE 1 — CagriSema for obesity without diabetes

Obesity or overweight with at least one comorbidity, without diabetes

At 68 weeks, CagriSema produced about 22.7% mean body-weight reduction under the trial-product estimand and was superior to semaglutide, cagrilintide, and placebo.

2025·Phase 3a, double-blind, randomized, placebo-controlled·n=1206High quality

REDEFINE 2 — CagriSema for overweight/obesity with type 2 diabetes

Type 2 diabetes with overweight or obesity

CagriSema produced clinically meaningful weight loss and glycemic improvement versus placebo over 68 weeks in a T2D population.

2023·Multicenter, randomized, double-blind, active-controlled·n=92Moderate quality

Phase 2 CagriSema in type 2 diabetes

Type 2 diabetes with overweight or obesity

The combination produced greater weight loss and glycemic improvement than either semaglutide or cagrilintide alone over 32 weeks.

What the evidence shows

Does CagriSema produce large weight loss?

Yes. REDEFINE 1 reported about 22.7% mean weight loss at 68 weeks under the trial-product estimand and showed superiority over semaglutide, cagrilintide, and placebo.

Well-supported

Is the amylin component meaningful?

Yes. Because REDEFINE 1 included both monotherapy arms, the trial directly supports that cagrilintide adds clinically meaningful weight loss on top of semaglutide.

Well-supported

Is CagriSema better than tirzepatide?

Unknown. Cross-trial comparisons place CagriSema in the same high-efficacy tier, but direct head-to-head superiority is not established.

More research needed

Is CagriSema FDA-approved?

No. The FDA NDA was filed in December 2025, but CagriSema remains investigational until FDA review is complete.

Not yet demonstrated

Safety & side effects

The main tolerability issue is gastrointestinal: nausea, vomiting, diarrhea, constipation, and appetite-related effects. That is expected from GLP-1 and amylin biology. REDEFINE 1 and REDEFINE 2 did not create a mature post-marketing safety dataset; they created a pre-approval trial dataset.[1][2]

Practical safety gaps:

  • No post-marketing pharmacovigilance.
  • No long-term real-world persistence data.
  • No completed cardiovascular outcomes trial specific to CagriSema.
  • Unknown rare-event profile in broader, less-selected populations.
  • Dose escalation and dose flexibility appear important for tolerability.

The safety question is not whether CagriSema has side effects. It does. The question is whether the additional weight loss from adding amylin is worth the added tolerability burden for a given patient population. That answer will depend on FDA labeling, payer coverage, and real-world use.

CagriSema is not FDA-approved as of this review. Novo Nordisk filed its US NDA for weight management on December 18, 2025.[5] The product remains investigational until FDA review is complete.

For sport, CagriSema should be treated conservatively. It is not listed by name on the WADA 2026 list, but non-approved pharmacological substances are prohibited under S0. Because CagriSema contains an investigational component, athletes should not treat it as permitted without formal anti-doping guidance.[8]

Comparisons

Profile Mechanism Regulatory status Evidence readout
Semaglutide GLP-1 receptor agonist FDA-approved Strongest approved GLP-1 evidence base
Tirzepatide GIP + GLP-1 agonist FDA-approved Approved high-efficacy dual incretin
CagriSema Semaglutide + cagrilintide NDA filed; not approved Phase 3 obesity and T2D evidence
Amycretin Single-molecule GLP-1 + amylin agonist Investigational Strong early oral and injectable signals
Retatrutide GIP + GLP-1 + glucagon agonist Investigational Phase 3 program ongoing

Related content

Peptide

Cagrilintide Profile

The long-acting amylin analogue half of CagriSema, now moving through a dedicated Phase 3 monotherapy program.

Peptide

Semaglutide Profile

The FDA-approved GLP-1 receptor agonist half of CagriSema.

Peptide

Amycretin Profile

Novo Nordisk's single-molecule GLP-1/amylin agonist, now called zenagamtide in newer pipeline materials.

Peptide

Tirzepatide Profile

The approved dual GIP/GLP-1 benchmark for high-efficacy metabolic peptide therapy.

References

  1. [1]
    Garvey WT, Blüher M, Osorto Contreras CK, et al.. “Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.” N Engl J Med. 2025. 393(7):635-647 DOI PubMedRCT

    REDEFINE 1. Large Phase 3a trial in adults without diabetes; compared CagriSema with semaglutide, cagrilintide, and placebo.

  2. [2]
    Davies MJ, Bajaj HS, Broholm C, et al.. “Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.” N Engl J Med. 2025. 393(7):648-659 DOI PubMedRCT

    REDEFINE 2. Phase 3a trial in adults with T2D and overweight or obesity; placebo-controlled with lifestyle intervention.

  3. [3]
    Frias JP, Deenadayalan S, Erichsen L, et al.. “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.” Lancet. 2023. 402:720-730 DOI PubMedRCT

    Small Phase 2 trial (n=92) comparing the combination with each component in people with T2D.

  4. [4]
    Enebo LB, Berthelsen KK, Kankam M, et al.. “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.” Lancet. 2021. 397(10286):1736-1748 DOI PubMedRCT

    Early combination safety and PK/PD trial. Short duration and small cohorts; useful for dose-escalation and tolerability context.

  5. [5]
    Novo Nordisk. “Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management.” 2025. LinkReview

    Company announcement of FDA NDA submission. Regulatory milestone, not an approval decision.

  6. [6]
    Novo Nordisk. “CagriSema demonstrated superior HbA1c reduction of 1.91%-points and weight loss of 14.2% in adults with type 2 diabetes in the REIMAGINE 2 trial.” 2026. LinkRCT

    Topline company announcement. Peer-reviewed publication pending.

  7. [7]
    Novo Nordisk. “Novo Nordisk Annual Report 2025 — Innovation and therapeutic focus.” 2026. LinkReview

    Corporate annual report summarizing CagriSema, cagrilintide, and zenagamtide program status.

  8. [8]
    World Anti-Doping Agency. “The 2026 Prohibited List.” 2026. LinkReview

    Used for S0 non-approved-substance regulatory context.

Medical disclaimer

Peptide Garden is an educational resource, not a medical provider. This page is informational and does not constitute medical advice. CagriSema is investigational and not FDA-approved; do not use unapproved products sold as CagriSema outside regulated clinical care or clinical trials.