Library / Peptides / Weight Management / CagriSema
Emerging evidence · Grade B

CagriSema

CagriSema (Cagrilintide / Semaglutide)
Score
68 / 100
Class
Amylin + GLP-1 combo
Route
Once weekly (SC)
Status
Phase 3, under review
TL;DR
01
A fixed-dose, once-weekly injectable combination of two peptides — cagrilintide (an amylin analog) plus semaglutide (a GLP-1) — from Novo Nordisk.
02
In its phase 3 obesity trial (REDEFINE 1), it produced about 20.4% weight loss at 68 weeks versus ~3% placebo.
03
That's a strong result — but it landed below Novo Nordisk's own ~25% pre-trial projection, which disappointed expectations.
04
In type 2 diabetes (REDEFINE 2) it delivered ~13.7% weight loss plus strong glycemic control.
05
It is investigational and under regulatory review, not yet approved; it pairs two mechanisms (amylin + GLP-1) covered individually elsewhere in this library.
Wt loss (REDEFINE 1)
−20.4%
NEJM 2025 · 68 wk
vs Novo projection
Below ~25%
undershot expectations
Wt loss in T2D (REDEFINE 2)
−13.7%
68 wk
Components
Cagrilintide + sema
amylin + GLP-1
Status
Under review
not yet approved
Part 01 · How it works

Mechanism.

CagriSema stacks two different appetite mechanisms in one weekly shot: semaglutide (the familiar GLP-1 that curbs hunger) plus cagrilintide (an amylin analog that boosts the sense of fullness). Because the two work through separate pathways, combining them adds up to more weight loss than either alone — about 20% in the big phase 3 trial. The wrinkle is expectations: Novo Nordisk had signaled it might reach ~25%, so 20% read as a mild disappointment to the market, even though it's clinically strong. It's not approved yet.

Two appetite dials — GLP-1 and amylin — turned at once in a single weekly injection. Strong, but it came in a notch below the number people were hoping for.

Dual mechanism
Combines GLP-1 receptor agonism (semaglutide) with amylin receptor agonism (cagrilintide) — non-overlapping appetite pathways.
Additive weight loss
~20.4% at 68 weeks (REDEFINE 1), exceeding either component alone.
Glycemic effect
In T2D (REDEFINE 2), ~13.7% weight loss with strong HbA1c control.
Evidence stage
Positive phase 3 (REDEFINE), but below sponsor projection and not yet approved.
Part 02 · Dosing & administration

How it's taken.

Clinical · trial-validated

Values below describe how CagriSema has been administered in human clinical trials and/or approved labeling. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.

Trial
2.4 mg + 2.4 mg
Cagrilintide 2.4 mg co-formulated with semaglutide 2.4 mg, once weekly (REDEFINE dosing).
·
Doses below are from clinical trials, not instructions. CagriSema is not approved.
·
Once-weekly subcutaneous, co-titrated to limit GI effects.
·
Combines two mechanisms profiled separately (cagrilintide, semaglutide).
Need help with reconstitution?

Use the free peptide calculator for dilution, unit conversion, and injection volume.

Open calculator
Part 03 · Safety

Side effects, rare serious events, who shouldn't.

Common
Nausea
Part of the ~80% GI-event rate; mostly transient.
Common
Vomiting / diarrhea / constipation
Dual-mechanism GI burden.
Common
Injection-site reactions
Generally mild.
Common
Serious · rare
GI-related discontinuation
The main tolerability limit of the combination.
Notable
Class cautions
GLP-1/amylin class cautions (pancreatitis, gallbladder) pending full data.
Apply
Absolute · do not use
×
Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN-2) — a contraindication for the GLP-1 component
×
Known serious hypersensitivity to semaglutide, cagrilintide, or any formulation component
×
Pregnancy, breastfeeding, or active attempts to conceive (not studied; weight loss is discouraged in pregnancy)
×
History of pancreatitis or significant gallbladder disease, which warrant caution with GLP-1-based therapy
×
Severe gastrointestinal disease such as gastroparesis, where further delayed gastric emptying may be harmful
×
Use outside an approved clinical trial, given that CagriSema is investigational and unapproved
Relative · discuss first
!
History of pancreatitis — class caution
!
Personal/family history of MTC or MEN2 — GLP-1 component caution
!
Severe GI disease — delayed emptying
!
Pregnancy or breastfeeding — insufficient data
Interactions
Insulin
Combining with insulin can increase the risk of hypoglycemia; insulin dose reduction is often needed when adding GLP-1-based therapy
Major
Sulfonylureas (e.g., glipizide, glyburide)
Additive glucose-lowering raises hypoglycemia risk; dose reduction of the sulfonylurea may be warranted
Major
Oral medications generally (including oral contraceptives)
Delayed gastric emptying can alter the rate or extent of absorption of co-administered oral drugs
Moderate
Other GLP-1 receptor agonists or amylin analogs (e.g., tirzepatide, separate semaglutide)
Overlapping mechanisms with the components offer no added benefit and increase gastrointestinal and other class-related risks
Major
Alcohol
May compound gastrointestinal upset and, in those on other glucose-lowering agents, affect blood-sugar control
Moderate
Labs to monitor
HbA1c
Baseline and roughly every 3 months in study settings
Primary glycemic marker tracked in the diabetes trials; relevant if used in people with type 2 diabetes
Body weight / BMI and waist circumference
Baseline and at regular follow-up visits
Primary efficacy measure for the weight-management indication being studied
Blood pressure
Baseline and at routine visits
Notable reductions were seen with weight loss in trials; antihypertensive doses may need adjustment
Fasting glucose
Baseline and periodically, especially during dose titration
Secondary glycemic measure; helps assess response and hypoglycemia risk when combined with other glucose-lowering drugs
Lipid panel
Baseline and periodically
Cardiometabolic parameter commonly tracked alongside significant weight change
Part 04 · Evidence

How strong is the evidence?

68
Grade B
Grade B, Emerging. Large phase 3 data with ~20% weight loss make CagriSema a genuine high-efficacy contender, but it undershot its own projected target, remains unapproved, and its incremental value over a strong GLP-1 alone is still being debated (see cagrilintide).
Mechanistic plausibility
Rational dual GLP-1 + amylin mechanism.
82
Human evidence
Two large phase 3 trials (REDEFINE 1 & 2).
78
Efficacy vs expectation
~20.4% is strong but below the ~25% Novo signaled; near tirzepatide monotherapy.
60
Safety & tolerability
GI-dominant (79.6% in REDEFINE 1), mostly transient.
66
Independence
All pivotal trials Novo Nordisk-sponsored.
60
Part 05 · Research log

Every study we cite.

We list each study with its methodology, funding source, and our quality grade. Flagged studies aren't dismissed — they're tagged so you can weigh them.

01
2025
New England Journal of Medicine Industry funded
REDEFINE 1 — cagrilintide-semaglutide in overweight/obesity (phase 3)
−20.4% weight loss vs −3.0% placebo; GI adverse events 79.6% vs 39.9%, mostly transient. Fell below the ~25% pre-trial projection.
Phase 3a RCT, 68 wk, placebo- and active-controlled · n = 3,417 · Novo-sponsored; strong result, but below sponsor expectation.
PMID 40544433 ↗
High
02
2025
New England Journal of Medicine Industry funded
REDEFINE 2 — cagrilintide-semaglutide in overweight/obesity with T2D (phase 3)
−13.7% weight loss vs −3.4% placebo; 73.5% reached HbA1c ≤6.5%. GI events 72.5% vs 34.4%.
Phase 3a RCT, 68 wk, placebo-controlled · n = 1,206 · Novo-sponsored; smaller weight effect in T2D, as expected for the class.
PMID 40544432 ↗
High
Evidence against

What didn't work, and where the evidence is thin.

Every publication is incentivized to tell you a peptide works. We catalogue the null results, failed trials, and mechanism limits we found in the same literature — so you can weigh them against the upside, with your provider.

01
Strong — but it undershot its own target
Mechanism limit
NEJM (REDEFINE 1) · 2025
REDEFINE 1's −20.4% fell short of Novo Nordisk's ~25% pre-trial guidance and lands near tirzepatide monotherapy, raising the question of how much the amylin partner adds over a strong GLP-1 alone.
What this means: CagriSema is effective, but its incremental value over simpler regimens — and whether the added complexity is worth it — is not yet settled.
PMID 40544433 ↗
02
GI-heavy and not yet approved
Safety signal
NEJM (REDEFINE 2) · 2025
Gastrointestinal adverse events affected the large majority of participants (though mostly transient), and CagriSema remains under regulatory review without approval.
What this means: The tolerability tax is real, and no regulator has yet cleared it — treat it as promising late-stage, not established.
PMID 40544432 ↗
Part 06 · Cost & access

Where it's available, at what price.

United States
Investigational
Not approved; phase 3 complete and under regulatory review.
N/A pending approval
European Union
Investigational
Under review; not approved.
N/A
United Kingdom
Investigational
Not approved.
N/A
Canada
Investigational
Not approved.
N/A
The Peptide Column takes no affiliate commission from any source. CagriSema is an investigational combination under regulatory review with no approval; any product sold as 'CagriSema' now is unregulated. We link only to clinician-directed care, never to sellers.
Part 07 · Your appointment

Questions to bring.

01
CagriSema is not FDA-approved yet — is there an open clinical trial I might be eligible for, rather than a compounded or unapproved source?
02
How does the expected weight change and side-effect profile compare with approved options like semaglutide (Wegovy) or tirzepatide (Zepbound) that I could use now?
03
Gastrointestinal side effects were very common in the trials — how would we titrate the dose and manage nausea, vomiting, or diarrhea if I started a GLP-1-based therapy?
04
Given my personal and family history (including any thyroid cancer, MEN-2, pancreatitis, or gallbladder disease), is a GLP-1/amylin combination appropriate for me?
References

Every citation, numbered.

Citation list. For our editorial read of each study — including bias flags and quality grades — see the Research log above.

  1. 01.
    REDEFINE 1 — cagrilintide-semaglutide in overweight/obesity (phase 3) · New England Journal of Medicine, 2025 · PMID 40544433 ↗
  2. 02.
    REDEFINE 2 — cagrilintide-semaglutide in overweight/obesity with T2D (phase 3) · New England Journal of Medicine, 2025 · PMID 40544432 ↗
  3. 03.
    ClinicalTrials.gov. REDEFINE 1 (NCT05567796), REDEFINE 2 (NCT05394519) · Source ↗