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Cagrilintide

An investigational long-acting amylin analogue from Novo Nordisk, studied alone and combined with semaglutide as CagriSema, which is under FDA review. Not yet approved.

Data refreshed 2026-09-24 · Based on 8 published references

Names

Generic: cagrilintide

Also called: NNC0174-0833, CagriSema (with semaglutide), cagri

Regulatory (US)

FDA approval: investigational

503A compounding: restricted

Molecule

Formula: C194H312N54O59S2

MW: 4409 g/mol

CAS: 1415456-99-3

PubChem entry

Origin

Discovered by: Novo Nordisk research

Developer: Novo Nordisk

What it is

Cagrilintide is a lab-made copy of amylin, a hormone the pancreas releases alongside insulin after meals. Amylin slows the stomach and signals fullness to the brain through a different route than GLP-1. Novo Nordisk engineered cagrilintide to last a week and to avoid clumping, a known problem with natural amylin.

On its own it produced slightly more weight loss than liraglutide in a mid-stage trial. Combined with semaglutide in one pen, called CagriSema, it produced about 20% weight loss in the main Phase 3 trial. Neither cagrilintide nor CagriSema is approved yet; CagriSema is under FDA review.

Cagrilintide (NNC0174-0833) is a 37-residue amylin analogue with substitutions at residues prone to β-sheet aggregation and a C20 fatty diacid attached through a linker for albumin binding. It is a dual amylin and calcitonin receptor agonist (DACRA), acting on calcitonin receptor and RAMP-associated amylin receptor complexes in the area postrema and hypothalamus. In a Phase 1b study its half-life was 159–195 hours, against 145–165 hours for co-administered semaglutide. The combination rationale is additive appetite suppression through non-overlapping central pathways, with the amylin component possibly offsetting some GLP-1 receptor agonist tolerance.

Who made it and when

Novo Nordisk developed it in the mid-2010s and published the chemistry in 2021. The company then ran it alone and with semaglutide. The Phase 3 program, REDEFINE, started in 2022 and reported its first results in December 2024. Novo Nordisk filed CagriSema with the FDA in December 2025, and a decision was expected in 2026.

Kruse and colleagues at Novo Nordisk described the medicinal chemistry in 2021. Phase 2 monotherapy (n=706) reported in 2021; Phase 2 CagriSema in T2D reported in 2023. The REDEFINE program includes REDEFINE 1 (obesity), REDEFINE 2 (obesity with T2D), REDEFINE 3 (cardiovascular outcomes, event-driven) and REDEFINE 4 (head-to-head vs tirzepatide). Novo Nordisk announced on 2025-12-18 that it had submitted a New Drug Application for once-weekly CagriSema (cagrilintide 2.4 mg and semaglutide 2.4 mg) for weight management in adults with obesity, or overweight with comorbidities. No FDA approval appears in Drugs@FDA as of September 2026. Patents are held by Novo Nordisk.

What the data say

Alone, the highest dose of cagrilintide produced about 11% weight loss in 26 weeks, slightly more than liraglutide. With semaglutide, the Phase 3 REDEFINE 1 trial showed about 20% loss over 68 weeks, compared with 15% for semaglutide alone and 3% for placebo; the figure was about 23% if everyone had stayed on treatment. Many participants did not stay on the full dose. In people with diabetes, CagriSema produced about 14% loss. In a direct comparison, it did not match tirzepatide.

Phase 2 monotherapy: 4.5 mg gave −10.8% at 26 weeks vs −3.0% placebo. REDEFINE 1 (n=3,417): CagriSema −20.4% vs semaglutide 2.4 mg −14.9%, cagrilintide 2.4 mg −11.5%, placebo −3.0% at 68 weeks (treatment-policy); −22.7% vs −2.3% by trial-product estimand. The flexible-dosing protocol meant only 57.3% of CagriSema participants were on the full 2.4/2.4 mg dose at the end of treatment. REDEFINE 2 (T2D, n=1,206): −13.7% vs −3.4%. REDEFINE 4 (n=809, open-label, 84 weeks) did not show non-inferiority to tirzepatide 15 mg (−23.0% vs −25.5% if all adhered). Gastrointestinal adverse events were the main tolerability issue, reported in 79.6% vs 39.9% on placebo in REDEFINE 1.

Regulatory picture

Cagrilintide has no approval anywhere. CagriSema, the combination with semaglutide, was submitted to the FDA in December 2025 and was still under review in September 2026. The FDA states that cagrilintide cannot legally be used in compounding in the United States and is not part of any FDA-approved drug. Anything sold online under this name is an unapproved drug.

Cagrilintide is investigational under IND. It is not a component of an approved product and has no USP monograph. FDA’s guidance page on unapproved GLP-1 drugs states that cagrilintide cannot be used in compounding under federal law, so neither the 503A nor the 503B pathway is available. The CagriSema NDA was submitted to the FDA in December 2025; Novo Nordisk guided to a US decision in 2026, and no approval is listed in Drugs@FDA as of September 2026. Any approval would cover the fixed-dose combination product, not cagrilintide as a stand-alone drug.

Doses reported in trials

Doses reported in studies, exactly as the cited trial reported them. They are not personal dosing instructions. Population, route and schedule matter more than the number.

TrialPhaseStatusPopulationDoseResult
Phase 2 monotherapy study
NCT03856047
2Completed706 adults with obesity or overweight plus hypertension or dyslipidaemia, no diabetes0.3, 0.6, 1.2, 2.4 or 4.5 mg subcutaneous once weekly vs placebo and liraglutide 3 mg daily, 26 weeks−10.8% body weight at 4.5 mg vs −3.0% placebo and −9.0% liraglutide at 26 weeks (Lau et al., Lancet 2021)
Phase 2 CagriSema in type 2 diabetes
NCT04982575
2Completed92 adults with type 2 diabetes and overweight or obesityCagrilintide 2.4 mg plus semaglutide 2.4 mg once weekly vs each alone, 32 weeks−15.6% body weight with CagriSema vs −5.1% semaglutide and −8.1% cagrilintide; HbA1c −2.2 points (Frias et al., Lancet 2023)
REDEFINE 1
NCT05567796
3Active, not recruiting (primary 68-week results published)3,417 adults with obesity or overweight plus comorbidity, no diabetesCagrilintide 2.4 mg plus semaglutide 2.4 mg once weekly (CagriSema) vs each alone vs placebo, 68 weeks−20.4% body weight with CagriSema vs −14.9% semaglutide, −11.5% cagrilintide and −3.0% placebo, treatment-policy estimand (Garvey et al., NEJM 2025)
REDEFINE 2
NCT05394519
3Completed1,206 adults with obesity or overweight and type 2 diabetesCagriSema 2.4 mg / 2.4 mg once weekly vs placebo, 68 weeks−13.7% body weight vs −3.4% placebo, treatment-policy estimand (Davies et al., NEJM 2025)
REDEFINE 4
NCT06131437
3Completed809 adults with obesity (BMI 30 or higher) and at least one comorbidity, no diabetesCagriSema 2.4 mg / 2.4 mg once weekly vs tirzepatide 15 mg once weekly, open-label, 84 weeksDid not meet its primary endpoint of non-inferiority to tirzepatide: −23.0% vs −25.5% if all participants adhered, −20.2% vs −23.6% by treatment-regimen estimand (Novo Nordisk, February 2026)

Enforcement history

Reported side effects

Interactions

Contraindications

Storage

No approved product exists, so there is no label storage guidance. Supplier claims for research-grade material are not label data.

Product characteristics

Form: Investigational solution for subcutaneous injection; in CagriSema, co-formulated with semaglutide in one pen

Stability: Lipidated with a C20 fatty diacid; half-life of 159–195 hours (about 7–8 days) in a Phase 1b study supports once-weekly dosing

Compound information

Synthetic 37-residue amylin analogue with substitutions to prevent fibrillation and a C20 diacid for albumin binding. It is a dual amylin and calcitonin receptor agonist. PubChem lists the formula as C194H312N54O59S2 (CID 171397054).

References

This page summarises the published sources below. PeptideBasics101 does no original research. Trial doses and results are reported as the cited study or label reported them. Sources can themselves be wrong or superseded; if you find a statement here that does not match its source, please tell us through our corrections process. Sources were last checked on 2026-09-24.

  1. Lau DCW et al. Once-weekly cagrilintide for weight management in people with overweight and obesity. Lancet 2021 (doi.org)
  2. Frias JP 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. Lancet 2023 (doi.org)
  3. Garvey WT et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1). NEJM 2025 (nejm.org)
  4. Davies MJ et al. Cagrilintide–semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2). NEJM 2025 (nejm.org)
  5. Kruse T et al. Development of cagrilintide, a long-acting amylin analogue. J Med Chem 2021 (doi.org)
  6. Novo Nordisk: CagriSema submitted to the FDA (press release, 2025-12-18) (prnewswire.com)
  7. Novo Nordisk: REDEFINE 4 headline results (company announcement, 2026-02-23) (globenewswire.com)
  8. PubChem: cagrilintide (pubchem.ncbi.nlm.nih.gov)

Clinical trial entries in the table above link to their ClinicalTrials.gov registry records. Spotted an error? See corrections.

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