CagriSema
Cagrilintide and semaglutide together in one weekly injection.
In the phase 3 REDEFINE 1 trial, people lost 20.4% of body weight over 68 weeks against 3.0% on placebo — 22.7% among those who stayed on treatment [1]. Submitted to the US FDA in December 2025; not approved anywhere yet [9].
Written by Michael Carroll — Owner, Director of Research · Reviewed by the Peptide Initiative Research Team
Suggested dose
0.25 – 2.4 mg
0.25 mg each
Weeks 1-4 — escalation step 1
0.5 mg each
Weeks 5-8 — escalation step 2
1.0 mg each
Weeks 9-12 — escalation step 3
1.7 mg each
Weeks 13-16 — escalation step 4
2.4 mg each
Week 17 on — maintenance (52 weeks in phase 3)
Compound profile
Scientific & efficacy data
Weight Management
Peptide profile
Strong human trials
CagriSema
2.4 mg each · Once weekly
Molecular formula
Cagrilintide C194H312N54O59S2 · Semaglutide C187H291N45O59
- Mol. weight
- Two peptides in one pen: ~4409 Da (cagrilintide) + ~4114 Da (semaglutide)
- CAS number
- 1415456-99-3 (cagrilintide) · 910463-68-2 (semaglutide)
- PubChem
- 171397054 (cagrilintide) · 56843331 (semaglutide)
- Developed · 2018-2019 (first combination trial)
- Novo Nordisk
Novo Nordisk A/S
Weight Management
The largest weight reduction documented in this library: 20.4% at week 68 vs 3.0% on placebo in 3,417 adults (22.7% among those treated as intended); more than half (53.6%) lost at least 20% of body weight vs 1.9% on placebo [1].
Blood Sugar Control
HbA1c fell 1.91 percentage points vs 1.75 on semaglutide 2.4 mg in 2,713 people with type 2 diabetes [5]; about 3 in 4 (73.5%) reached HbA1c 6.5% or less vs 15.9% on placebo in 1,206 adults [2].
Appetite Control
Two complementary satiety hormones — amylin through homeostatic and hedonic brain regions, GLP-1 through the hypothalamus — with an apparently additive effect on appetite reduction [6].
Dosing
How much do I take?
0.25 mg each, titrated to 2.4 mg each · once weekly
2.4 mg each
Once weekly
Covers all 5 dosing tiers · timing · dose-adjustment guidance.
Suitability
Is this right for me?
Best for weight loss & blood sugar control
Best for
Weight management
About 1 in 5 pounds of body weight lost (20.4%) over 68 weeks against 3.0% on placebo, and 22.7% among people treated as intended — shown in 3,417 adults without diabetes [1].
Type 2 diabetes with excess weight
13.7% weight loss against 3.4% on placebo at 68 weeks, and about 3 in 4 people (73.5%) reached an HbA1c of 6.5% or less against 15.9% on placebo — shown in 1,206 adults [2].
When semaglutide alone is not enough
Head-to-head at the same dose, the combination lost 5.5 percentage points more weight than semaglutide alone and 8.9 more than cagrilintide alone [1]; in 2,713 people with type 2 diabetes it also beat semaglutide 2.4 mg on HbA1c [5].
Consider alternatives if
Do not use if
Use with caution if
Not sure?
Compare CagriSema with similar peptides to find the best fit for your goals.
Administration
How do I use it?
Subcutaneous injection
Route
Subcutaneous injection
Best sites
Covers step-by-step technique.
Safety
Is it safe?
5 common side effects · 3 serious
The safety picture comes from randomised trials with over 4,000 participants exposed to the combination [1][2][3][5].
In REDEFINE 1 (3,417 adults without diabetes), about 4 in 5 people on CagriSema (79.6%) had gastrointestinal events — nausea, vomiting, diarrhoea, constipation or abdominal pain — against about 2 in 5 on placebo (39.9%); most were transient and mild to moderate, peaked during dose escalation, and eased once escalation ended [1].
Any adverse event: 92.3% vs 82.3% on placebo; serious adverse events: about 1 in 10 (9.8%) vs 6.1% on placebo, most commonly hepatobiliary and gastrointestinal disorders; discontinuation of an active drug for adverse events: 5.9% vs 3.5% [1].
Two deaths occurred among the 2,108 people in the combination group; the adjudicated causes were suicide and cancer, and mental-health scores (C-SSRS, PHQ-9) were similar across all four groups throughout the trial [1].
In type 2 diabetes the pattern held: gastrointestinal events 72.5% vs 34.4% on placebo (REDEFINE 2, 1,206 adults) [2]; adverse events 86.9% on the full dose vs 81.2% on semaglutide 2.4 mg alone and 70.5% on placebo (REIMAGINE 2, 2,713 adults) [5].
Heart rate rose slightly (+0.94 beats per minute at week 68, vs +1.17 on semaglutide, -3.31 on cagrilintide and -0.58 on placebo) [1]. In the 32-week phase 2 diabetes trial no level 2 or 3 hypoglycaemia and no fatal events were reported [3].
Phase 3 evidence across REDEFINE 1 [1], REDEFINE 2 [2] and REIMAGINE 2 [5], plus the phase 2 [3] and phase 1b [4] trials. CagriSema is not approved anywhere; the US FDA weight-management filing was submitted in December 2025 [9].
Because no CagriSema label exists, the contraindication and interaction statements on this page rest on the semaglutide component's approved label [8] and the trial protocol rules [7].
Common side effects · experienced by some users
Nausea
The most common class of events: gastrointestinal complaints affected 79.6% on CagriSema vs 39.9% on placebo in REDEFINE 1; prevalence peaked during dose escalation and decreased after it [1].
Management: Trial investigators could hold a dose step longer or step down rather than stop [1][7].
Vomiting
Part of the gastrointestinal cluster (79.6% vs 39.9% on placebo), mostly mild to moderate and transient [1].
Management: Same trial approach: delay escalation or reduce the dose [1].
Diarrhea
Part of the gastrointestinal cluster in every trial; in type 2 diabetes GI events hit 72.5% vs 34.4% on placebo [2].
Management: Usually transient; trials managed it through the escalation rules [1].
Constipation
Unlike nausea, its prevalence stayed relatively constant after dose escalation rather than fading [1].
Management: Persisted longer than other GI effects in the trial data — worth tracking across the whole treatment period [1].
Injection site reactions
Reported more often with CagriSema than placebo in REDEFINE 1 [1].
Management: The semaglutide label uses abdomen, thigh, or upper arm as injection sites [8].
Less common
These typically resolve with continued use or dose adjustment.
Stop and seek help if
- Suspicion of acute pancreatitis — the trial rule was to stop, measure amylase and lipase, and resume only if not confirmed [7]
- Pregnancy [7]
- A serious hypersensitivity reaction [8]
- Any safety concern where your clinician judges continuing unsafe [7]
CagriSema is an investigational combination with no approved label anywhere. These stop rules are the ones its own trials used, plus the semaglutide component label — they are not medical advice. Decisions about starting, changing, or stopping belong with a qualified clinician.
With other peptides
- Caution:
With medications
- Caution:
- Caution:
With supplements
Effectiveness
How do I know it's working?
Strong human trials · first signs weeks 1-16
Evidence level
Strong human trials
(Phase 3 or FDA approved)
Regulatory status
Not approved anywhere
Submitted to the US FDA for weight management in December 2025 on the REDEFINE 1 and 2 trials; the type 2 diabetes pathway is still being discussed with regulators.
Onset of effects
Gradual — the full dose is only reached at week 16
How it works
CagriSema is two appetite signals in one weekly shot.
Semaglutide copies GLP-1, a gut hormone that tells your brain you are full, slows your stomach, raises insulin and lowers glucagon [6]. Cagrilintide copies amylin, a hormone released with insulin, which creates fullness through both the energy-balance and the reward regions of the brain [6].
Together the two signals cut appetite more than either does alone — in the first combination trial, adding cagrilintide 2.4 mg to semaglutide meant 17.1% weight loss at 20 weeks against 9.8% on semaglutide alone [4].
The deeper mechanism
Semaglutide is a GLP-1 receptor agonist acting on hypothalamic appetite centres, pancreatic beta cells (glucose-dependent insulin secretion), alpha cells (glucagon suppression) and gastric motility [6].
Cagrilintide is a lipidated long-acting amylin analogue with activity at amylin receptors, signalling satiety through homeostatic and hedonic brain regions [6]; the REDEFINE 1 investigators attribute the combination's effect to complementary direct actions in the hypothalamus, hindbrain and septum [1].
Pharmacokinetically the two do not interfere: cagrilintide exposure is dose-proportional and leaves semaglutide exposure and elimination unchanged, with half-lives of 159-195 hours (cagrilintide) and 145-165 hours (semaglutide) supporting once-weekly co-dosing [4].
What to expect
Weeks 1-16
Weeks 17-32
What you might notice
- In the 32-week phase 2 diabetes trial, weight was down 15.6% by week 32 (vs 5.1% on semaglutide alone), and time in glucose range had risen from 45.9% to 88.9% [3]
What's normal
- Nausea and vomiting fade after escalation; constipation tended to persist [1]
Weeks 33-68
Signs it's working
physical
clinical
subjective
- Reduced appetite through both the amylin and GLP-1 satiety pathways — the mechanisms are additive in the published pharmacology [6]
Not seeing results? Common reasons
- Still in the escalation phase — the full 2.4 mg dose is only reached at week 16, and trial weight curves kept falling well past it [1][7]
- Held at a submaximum dose — allowed by the trials; 57.4% of REDEFINE 1 participants were on the maximum dose at week 68 and the group still averaged 20.4% weight loss [1]
- Missed doses — the protocol restarted one step lower after 3-4 weeks without a dose, two steps lower after 4-5 weeks, and from the lowest dose after 5 or more [7]
Key research
Questions
Frequently asked
Is CagriSema approved?
Why do I see both 20.4% and 22.7% quoted for the weight loss?
Two ways of counting the same trial. 20.4% counts everyone randomised, whether or not they stayed on the drug (the treatment-policy estimand); 22.7% counts people while treated as intended (the trial-product estimand) [1]. Both are real REDEFINE 1 numbers — one answers "what happens if it is prescribed", the other "what happens if you take it".
Is this the same as taking cagrilintide and semaglutide separately?
The phase 2 trial gave the two drugs as separate injections on the same day, co-escalated in matching steps [3][7]. Phase 3 used a fixed-dose dual-chamber pen delivering both in one injection [1]. No trial tested improvised combinations of separately sourced products — stacking the two components yourself is community practice, not the studied product (community-reported, not peer-reviewed).
How much better is it than semaglutide alone?
In REDEFINE 1, weight fell 20.4% on the combination against 14.9% on semaglutide 2.4 mg — 5.5 percentage points more [1]. In type 2 diabetes, HbA1c fell 1.91 percentage points against 1.75 on semaglutide 2.4 mg — a 0.16-point edge that was statistically significant (p=0.0035) [5]. The gastrointestinal cost was real but modest: 86.9% vs 81.2% had adverse events in that head-to-head [5].
Ready for the protocol?
Every dosing tier, administration route, timing note, and dose-adjustment rule for CagriSema, on one page.