CagriSema dosing & administration
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
Dosing
How much do I take?
Subcutaneous: A small injection into the fatty layer just under the skin — the same way insulin is given.
Bioavailability High — most of the dose reaches your bloodstream, just more gradually than an IV.
0.25 mg each
Frequency
Once weekly
Duration
Weeks 1-4 — escalation step 1
0.5 mg each
Frequency
Once weekly
Duration
Weeks 5-8 — escalation step 2
1.0 mg each
Frequency
Once weekly
Duration
Weeks 9-12 — escalation step 3
1.7 mg each
Frequency
Once weekly
Duration
Weeks 13-16 — escalation step 4
Escalation step 4 in the trial protocol, held 4 weeks before the maintenance dose [7].
2.4 mg each
Frequency
Once weekly
Duration
Week 17 on — maintenance (52 weeks in phase 3)
The maintenance dose in every phase 3 trial: 2.4 mg of each drug from week 16, held through a 52-week maintenance period in REDEFINE 1 [1]. Investigators could delay escalation or reduce the dose, and participants could stay on a submaximum dose — at week 68, 57.4% of the combination group was on the maximum dose, against 70.9% on semaglutide alone, 82.5% on cagrilintide alone and 70.6% on placebo [1]. Missed doses restarted one step lower per the protocol rules [7].
Timing
Best time to take
Once weekly on a fixed dosing day — the trials scheduled a dosing day and defined catch-up rules around it [7].
With food?
The semaglutide component is injected without regard to meals [8].
If stacking
This IS the stack — cagrilintide and semaglutide were co-escalated together in every trial [3]. Trials prohibited combining with any other GLP-1 receptor agonist, DPP-4 inhibitor, or amylin analogue [7].
Adjusting your dose
Increase if
- You are tolerating the current step — the trial schedule stepped up every 4 weeks until the 2.4 mg maintenance dose [7]
- After a dose reduction — the protocol recommended at least one attempt to re-escalate to the maintenance dose [7]
Decrease if
- The current dose is not tolerated — trials let participants stay at a lower step rather than stop entirely [1][7]
- BMI falls below 22.5 kg/m2 with continued weight loss — a protocol-specified reason to reduce the maintenance dose [7]
- Persistent nausea or vomiting during escalation — investigators could postpone the next step [1]
Signs of right dose
- Staying on a submaximum dose is documented and still effective: only 57.4% of REDEFINE 1 participants were on the maximum dose at week 68 [1]
Administration
How do I use it?
Injection
Safety
Is it safe?
Side effects
Commonly reported: Nausea, Vomiting, Diarrhea, Constipation, Injection site reactions
Less common: Fatigue and dizziness, Hair loss (alopecia), Gallbladder-related disorders
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.
Published research
What the studies show
Garvey WT, Blüher M, Osorto Contreras CK, et al. · 2025
The pivotal phase 3a obesity trial: 3,417 adults without diabetes randomised 21:3:3:7 to cagrilintide-semaglutide 2.4 mg each, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo for 68 weeks. Weight changed -20.4% on the combination vs -14.9% on semaglutide, -11.5% on cagrilintide and -3.0% on placebo; on the trial-product estimand the combination reached -22.7%. More than half (53.6%) lost at least 20% of body weight vs 1.9% on placebo. The fixed-dose pen was started at 0.25 mg of each drug and increased every 4 weeks to 2.4 mg by week 16, then held for 52 weeks.
Davies MJ, Bajaj HS, Broholm C, et al. · 2025
Phase 3a in 12 countries: 1,206 adults with type 2 diabetes and a BMI of 27 or more, randomised 3:1 to cagrilintide-semaglutide 2.4 mg each or placebo for 68 weeks. Weight changed -13.7% vs -3.4% on placebo; 73.5% reached an HbA1c of 6.5% or less vs 15.9% on placebo. Gastrointestinal adverse events: 72.5% vs 34.4%, mostly transient and mild or moderate.
Frias JP, Deenadayalan S, Erichsen L, et al. · 2023
The 32-week phase 2 trial: 92 adults with type 2 diabetes on metformin with or without an SGLT2 inhibitor, randomised 1:1:1 to CagriSema, semaglutide, or cagrilintide (all escalated to 2.4 mg), given as separate same-day injections. HbA1c fell 2.2 percentage points on CagriSema vs 1.8 on semaglutide and 0.9 on cagrilintide; weight fell 15.6% vs 5.1% and 8.1%. Time in glucose range rose from 45.9% to 88.9% on CagriSema. Adverse events: 68% vs 71% and 80% by arm; no fatal events.
Enebo LB, Berthelsen KK, Kankam M, et al. · 2021
The first human combination trial, 95 adults exposed: six cohorts randomised 3:1 to cagrilintide 0.16-4.5 mg or placebo, all with semaglutide 2.4 mg, co-escalated in 4-week steps over 16 weeks. At week 20, weight fell 17.1% with cagrilintide 2.4 mg plus semaglutide vs 9.8% on semaglutide plus placebo. Cagrilintide exposure was dose-proportional and did not affect semaglutide exposure; half-lives were 159-195 hours for cagrilintide and 145-165 hours for semaglutide.
Buse JB, Bajaj HS, Dalskov SM, et al. · 2026
Phase 3 head-to-head in 2,713 people with type 2 diabetes on metformin with or without an SGLT2 inhibitor, across 30 countries for 68 weeks. HbA1c fell 1.91 percentage points on cagrilintide-semaglutide 2.4 mg each vs 1.75 on semaglutide 2.4 mg (difference -0.16, p=0.0035). A 1.0 mg each arm (595 people) was also studied. Adverse events: 86.9% on the full-dose combination vs 81.2% on semaglutide 2.4 mg and 70.5% on placebo, mostly gastrointestinal.
D'Ascanio AM, Mullally JA, Frishman WH · 2024
Peer-reviewed review of the combination rationale: amylin, released with insulin from pancreatic beta cells, produces satiety through both the homeostatic and hedonic regions of the brain, while semaglutide reduces appetite via hypothalamic GLP-1 receptors, increases insulin, reduces glucagon, and delays gastric emptying. The separate but related mechanisms appear additive for appetite reduction.
Novo Nordisk A/S · 2021
The official trial protocol carrying the dose-escalation table: step 1 0.25 mg, step 2 0.5 mg, step 3 1.0 mg, step 4 1.7 mg — 4 weeks each — then the 2.4 mg maintenance dose from week 16, applied to both drugs together. Also defines the missed-dose rules (restart one step lower after 3-4 weeks missed, two steps after 4-5, from the lowest dose after 5+), dose-modification rules, and the prohibition on combining with other GLP-1 receptor agonists, DPP-4 inhibitors, or amylin analogues.
Novo Nordisk / U.S. FDA (DailyMed) · 2024
The approved US label for the semaglutide component. Boxed warning: semaglutide causes thyroid C-cell tumors in rodents at clinically relevant exposures; contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2, and after serious hypersensitivity to semaglutide. Injection sites: abdomen, thigh, or upper arm. Warns of increased hypoglycaemia risk combined with insulin or a sulfonylurea, and of temporary worsening of diabetic retinopathy with rapid glucose improvement.
Novo Nordisk A/S (company announcement — not peer-reviewed) · 2025
CagriSema for weight management was submitted to the US FDA in December 2025, based on the REDEFINE 1 and REDEFINE 2 pivotal trials. For type 2 diabetes, Novo Nordisk states it will approach authorities to discuss the regulatory pathway following REIMAGINE 1 and REDEFINE 3 results. Sponsor communication — the primary public source for filing status.
Want the full picture?
The complete CagriSema research profile: mechanism of action, clinical studies, effectiveness timeline, and FAQ.