CagriSema is the investigational once-weekly co-administration of cagrilintide 2.4 mg and semaglutide 2.4 mg. In REDEFINE 1 it reduced body weight by 20.4% versus 3.0% with placebo at 68 weeks.

Monograph in Incretin & amylin agonists

Cagrilintide

A long-acting amylin analog from Novo Nordisk, studied alone and — as CagriSema — together with semaglutide in phase 3.

Also called NN9838 · AM833 · CagriSema (with semaglutide)

Best evidence: Randomized human trials

Randomized phase 2 and phase 3 (REDEFINE) trials are published in The Lancet and NEJM; Drugs@FDA lists no approved application.

Investigational — not FDA-approved

Residue Editorial Team · updated Oct 19, 2026

What is Cagrilintide?

Cagrilintide is an investigational long-acting amylin analog given once weekly by injection. Alone, it reduced body weight by 6.0–10.8% versus 3.0% with placebo in a phase 2 trial11PubMedOnce-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 et al. Lancet. 2021.. Combined with semaglutide 2.4 mg as CagriSema, weight fell 20.4% versus 3.0% over 68 weeks in the phase 3 REDEFINE 1 trial22PubMedCoadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. Garvey WT et al. N Engl J Med. 2025.. It is not FDA-approved.

PubMed records: 12165 reviews
Trial publications: 1515 tagged RCT
Registered studies: 4418 active · 22 phase 3
Molecular weight: 4,409g/mol · PubChem
Evidence grade: BRandomized human trials

Key findings

Phase 2 (706 participants randomized to cagrilintide): weight reduction of 6.0–10.8% across 0.3–4.5 mg doses versus 3.0% with placebo; the 4.5 mg dose beat liraglutide 3.0 mg (10.8% vs 9.0%)1.
REDEFINE 1 (3,417 adults with overweight or obesity): cagrilintide–semaglutide produced −20.4% versus −3.0% at 68 weeks2.
REDEFINE 2 (1,206 adults with type 2 diabetes): −13.7% versus −3.4%, with 73.5% reaching HbA1c ≤6.5% versus 15.9%33PubMedCagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. Davies MJ et al. N Engl J Med. 2025..
Gastrointestinal adverse events affected 79.6% on cagrilintide–semaglutide versus 39.9% on placebo in REDEFINE 1, mainly transient and mild to moderate2.
Cagrilintide's half-life was 159–195 hours in the phase 1b trial, and it did not alter semaglutide exposure44PubMedSafety, 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 et al. Lancet. 2021..

Written by Residue Editorial Team

Reviewed by Residue Editorial Team · source-by-source check, Oct 19, 2026

First published October 19, 2026

Last updated October 19, 2026

Registry data October 19, 2026 · How we grade · Markdown + sources

What is Cagrilintide, chemically?

**Identifiers** retrieved from PubChem.
PubChem CID	171397054 “Cagrilintide”
Formula	C194H312N54O59S2
Molecular weight	4,409 g/mol
CAS (as listed)	1415456-99-3
InChIKey	LDERDVMBIYGIOI-IZVMHKDJSA-N
Length	38 residues
Half-life (reported)	159–195 hours in a phase 1b study4
Route in trials	Once-weekly subcutaneous injection
Originator	Novo Nordisk
Mechanism	Long-acting amylin receptor agonist (amylin analog)

Hydrophobic
Polar
Basic (+)
Acidic (−)
Gly / Pro / Cys
Non-standard

Figure 1. Residue sequence of Cagrilintide (38 positions) as recorded in PubChem CID 171397054. “X” marks 1 non-standard, D-form or chemically modified position; see the condensed notation.

How does Cagrilintide work?

Amylin is a peptide hormone co-secreted with insulin by pancreatic beta cells. Cagrilintide is a long-acting amylin analog designed for once-weekly dosing; its development rationale is a mechanism distinct from, and complementary to, GLP-1 receptor agonism1. The phase 1b trial showed cagrilintide exposure rose in proportion to dose without changing semaglutide's exposure or elimination, which is what made a fixed-dose combination feasible4.

How long does Cagrilintide last in the body?

In the phase 1b trial in 96 people with overweight or obesity, cagrilintide (0.16–4.5 mg) had a half-life of 159–195 hours and a median time to peak of 24–72 hours. Semaglutide 2.4 mg given alongside had a half-life of 145–165 hours4.

What did the clinical trials find?

Cagrilintide alone. A Lancet phase 2 dose-finding trial randomized 706 participants to five doses of cagrilintide (0.3–4.5 mg), 99 to liraglutide 3.0 mg and 101 to placebo. Weight fell 6.0–10.8% (6.4–11.5 kg) with cagrilintide against 3.0% with placebo, and the top dose produced more weight loss than liraglutide (10.8% versus 9.0%). Discontinuation was similar across groups, at 10% overall1.

CagriSema in type 2 diabetes (phase 2). In 92 participants over 32 weeks, weight fell 15.6% with CagriSema versus 5.1% with semaglutide and 8.1% with cagrilintide. HbA1c fell 2.2 points with CagriSema and 1.8 with semaglutide, a difference that did not reach statistical significance (p=0.075). Time in glucose range rose to 88.9% with CagriSema55PubMedEfficacy 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 et al. Lancet. 2023..

REDEFINE 1. In 3,417 adults with overweight or obesity, 2,108 were assigned to cagrilintide–semaglutide and 705 to placebo, with smaller single-agent arms. Mean weight change at 68 weeks was −20.4% versus −3.0% (difference −17.3 points)2.

REDEFINE 2. In 1,206 adults with obesity and type 2 diabetes, weight change was −13.7% versus −3.4%, and 73.5% versus 15.9% reached an HbA1c of 6.5% or less3.

What adverse events were reported in trials?

Gastrointestinal events dominate. With cagrilintide alone, 41–63% of participants had gastrointestinal events versus 32% with placebo, mostly nausea (20–47% versus 18%), and administration-site reactions were also common1. In REDEFINE 1, gastrointestinal events affected 79.6% on the combination versus 39.9% on placebo2; in REDEFINE 2 the figures were 72.5% versus 34.4%3. Most were transient and mild to moderate.

Is Cagrilintide FDA-approved?

**Table 1. Regulatory status of Cagrilintide in the United States** — from Drugs@FDA (openFDA) and FDA’s bulk-substance compounding categories, as fetched.
Record	Status	Source
FDA approval	No approved application Drugs@FDA returned no application for “cagrilintide”.	openFDA

Cagrilintide has no approved application in Drugs@FDA, alone or in combination, and does not appear on FDA's compounding category lists. Any product sold as "cagrilintide" outside a trial is not an approved drug.

What is still unknown?

Single-agent arms in phase 3. REDEFINE 1 included cagrilintide-only and semaglutide-only groups2; comparisons among them deserve close reading of the full paper.
Long-term safety and outcomes beyond 68 weeks are being studied in registered trials66TrialClinicalTrials.gov registry search: cagrilintide OR CagriSema. 44 registered studies at fetch..

What effects has Cagrilintide shown, by body system?

Each row is graded separately using the Residue evidence scale: a compound can carry an A for one use and a D for another.

**Table 2.** Research-observed effects of Cagrilintide by body system, with the strongest evidence available for each.
System	What was observed	Grade
Body weight (alone)	6.0–10.8% reduction at 26 weeks across doses versus 3.0% placebo1.	B
Body weight (with semaglutide)	−20.4% at 68 weeks in REDEFINE 12; −13.7% in type 2 diabetes3.	B
Glycemic control	In a 32-week phase 2 diabetes trial, CagriSema lowered HbA1c by 2.2 points versus 1.8 with semaglutide (difference not significant) and 0.9 with cagrilintide alone5.	B
Gastrointestinal (adverse)	GI events 41–63% versus 32% with placebo for cagrilintide alone, mainly nausea1.	B

How much research is there on Cagrilintide?

Figure 2. PubMed records per publication year matching (cagrilintide[tiab] OR CagriSema[tiab]) — 121 in total; peak 55 in 2026. The 2026 bar is year-to-date (hatched). Volume of literature is not evidence of efficacy. Run this query on PubMed.

Registered studies of Cagrilintide by phase and status
Phase	Studies	Breakdown
Phase 1	17	10 completed, 7 active or recruiting, 0 stopped, 0 other
Phase 2	5	4 completed, 0 active or recruiting, 1 stopped, 0 other
Phase 3	22	10 completed, 11 active or recruiting, 1 stopped, 0 other

Figure 3. 44 studies on ClinicalTrials.gov match the registry search cagrilintide OR CagriSema. Multi-phase studies are counted at their highest phase. Open the full trial feed

Compare and continue

Cagrilintide vs semaglutideComparison
SemaglutideIncretin & amylin agonists
TirzepatideIncretin & amylin agonists
RetatrutideIncretin & amylin agonists

Questions readers ask

What is CagriSema?

CagriSema is the investigational once-weekly co-administration of cagrilintide 2.4 mg and semaglutide 2.4 mg3. In REDEFINE 1 it reduced body weight by 20.4% versus 3.0% with placebo at 68 weeks2.

Is cagrilintide FDA-approved?

No. At our last fetch, openFDA Drugs@FDA returned no application for cagrilintide. Phase 3 trials are active or recruiting on ClinicalTrials.gov6.

What are the side effects of cagrilintide?

The most frequent were gastrointestinal (nausea, constipation, diarrhea) and injection-site reactions. Gastrointestinal events affected 41–63% on cagrilintide versus 32% on placebo, primarily nausea1.

How long does cagrilintide last in the body?

In a phase 1b study its half-life ranged from 159 to 195 hours (about 7–8 days), with peak levels 24–72 hours after injection4.

How does cagrilintide compare with semaglutide?

In a small phase 2 diabetes trial, cagrilintide alone reduced weight by 8.1% and semaglutide alone by 5.1% at 32 weeks, while the combination reduced it by 15.6%5. See our cagrilintide vs semaglutide comparison.

What is cagrilintide?

Cagrilintide is an investigational long-acting amylin analog given once weekly. Alone it reduced weight by 6.0–10.8% in phase 21; with semaglutide 2.4 mg as CagriSema it reduced weight by 20.4% in REDEFINE 12. It is not FDA-approved.

References

Every source below was retrieved from its official API or page and cached on the data-edition date. Numbers match the margin notes.

1 PubMed Lau DCW, Erichsen L, Francisco AM, et al. 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. Lancet 2021. PMID 34798060; doi:10.1016/S0140-6736(21)01751-7.
2 PubMed Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2025. PMID 40544433; doi:10.1056/NEJMoa2502081.
3 PubMed 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. PMID 40544432; doi:10.1056/NEJMoa2502082.
4 PubMed 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. PMID 33894838; doi:10.1016/S0140-6736(21)00845-X.
5 PubMed 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. PMID 37364590; doi:10.1016/S0140-6736(23)01163-7.
6 ClinicalTrials.gov ClinicalTrials.gov registry search: cagrilintide OR CagriSema. 44 registered studies at fetch.