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 · Editorial standards
Subcutaneous
Route
3 recommended
Sites
Once weekly
Frequency
Location
Site 01
Abdomen
Pinch the skin 2 inches from navel. Avoid the area directly around the belly button. Rotate between left and right sides.
Site 02
Outer Thigh
Middle third of the outer thigh. Keep at least 4 inches above the knee and below the hip. Alternate legs each injection.
Site 03
Upper Arm
Back or outer area of the upper arm. This site may require assistance from another person for proper technique.
Rotate between 3 sites to prevent tissue buildup and ensure consistent absorption.
Pro tip
Rotate your injection sites with each dose to prevent lipohypertrophy (buildup of fatty tissue). Keep a simple log of where you last injected.
Step by step
In trials the combination came as pre-filled pens: a dual-chamber single-dose pen delivering both drugs in one injection in phase 3 [1]; phase 2 used two separate pre-filled pens given the same day [3][7]
Inject subcutaneously in the abdomen, thigh, or upper arm, per the semaglutide component label [8]
Pro tip
This peptide uses subcutaneous injection. Inject at a 45-90 degree angle into pinched skin. Aspirate before injecting to ensure you haven't hit a blood vessel.
Timing
Optimal timing
Best time
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].
Stacking notes
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].
Dosing tiers
Dose
0.25 mg each
Frequency
Once weekly
Duration
Weeks 1-4 — escalation step 1
Both phase 3 REDEFINE trials initiated the fixed-dose pen at 0.25 mg of each drug [1]. Escalation step 1 in the trial protocol, held 4 weeks [7]. Human trials; 2,108 participants took the combination in REDEFINE 1 alone [1].
Dose
0.5 mg each
Frequency
Once weekly
Duration
Weeks 5-8 — escalation step 2
Escalation step 2 in the trial protocol, held 4 weeks [7]. The same participants stepped up from 0.25 mg — this is a true titration ladder, confirmed from the protocol and trial methods [1][7].
Dose
1.0 mg each
Frequency
Once weekly
Duration
Weeks 9-12 — escalation step 3
Escalation step 3 in the trial protocol, held 4 weeks [7]. Also studied as a maintenance dose in its own right: REIMAGINE 2 carried a cagrilintide-semaglutide 1.0 mg each arm of 595 people with type 2 diabetes for 68 weeks [5].
Dose
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].
Dose
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].
Important
When to stop
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.
Clean technique checklist
Wash hands thoroughly with soap and water before handling supplies
Swab vial tops and injection site with alcohol and let dry
Never touch the needle tip or allow it to contact non-sterile surfaces
Use a new syringe and needle for each injection
Dispose of used sharps in a proper sharps container
Store reconstituted peptides according to the storage instructions above
Published research
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.