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Investigational combination · two separate component doses
CagriSema
CagriSema has two component doses. Read the separate weight trials. In REDEFINE 4, it did not meet the main test against tirzepatide.
- Keep the two component amounts separate.
- The trials enrolled different groups, so their weight results are not a head-to-head comparison.
- REDEFINE 4 did not meet its main test of noninferiority against tirzepatide.
CagriSema has two drugs. These are cagrilintide and semaglutide. This research drug is given under the skin once weekly.
The key REDEFINE arms named two amounts: 2.4 mg cagrilintide plus 2.4 mg semaglutide. Each amount belongs to a separate drug. They must not be added into one total dose.
Peer-reviewed Phase 3 trials lasted 68 weeks. They used the treatment-policy estimate for mean weight change. In adults without diabetes, CagriSema gave −20.4% versus −3.0% with placebo.
In adults with type 2 diabetes, the figures were −13.7% versus −3.4%. The trials enrolled different groups. They are not a head-to-head comparison.
The company also reported REDEFINE 4 results. CagriSema did not meet its main noninferiority test against tirzepatide. Current US sources were checked.
No approved CagriSema or cagrilintide product was found. The company reported an FDA filing. A filing is not an approval.
What matters first
- Keep the two doses separate: The amounts are 2.4 mg cagrilintide plus 2.4 mg semaglutide. Do not add them. Semaglutide has its own approval. That does not extend to cagrilintide or the combination.
- Name the measure with each result: Treatment-policy estimates include all randomized people, even if they did not follow treatment. Sponsor trial-product or efficacy estimates ask a different question. That question depends on treatment adherence. These headline numbers cannot replace each other.
- REDEFINE 4 failed its main test: This trial directly tested the drug against tirzepatide. It did not meet noninferiority. The early company figures do not prove the drugs are equivalent. Nor do they prove noninferiority or superiority.
- Target doses name the trial arms: REDEFINE 1 raised doses over 16 weeks. The trial also allowed dose changes. At week 68, only 57.3% of the combination group received the highest dose. That figure comes from the sponsor.
- Counts have different meanings: Papers count people randomized to trial arms. Registries list enrollment. A study marked
Completedhas ended. These do not all count the same thing. - The FDA decision remains unresolved in this review: The sponsor announced an NDA filing in December 2025. Current FDA and DailyMed searches found no product. This does not establish an NDA number or approved use. It supplies no approved label or plan for raising the dose.
Pivotal peer-reviewed evidence
Both main papers use the treatment-policy estimand. The authors say this fits the intention-to-treat principle. It estimates the effect across all randomized people.
It includes those who did not follow treatment.
| Trial | Population, control, and studied schedule | Treatment-policy result and limit |
|---|---|---|
| REDEFINE 1 | A 68-week, double-blind Phase 3a trial enrolled adults without diabetes who had BMI at least 30 kg/m², or at least 27 kg/m² with an obesity-related complication. All groups received lifestyle intervention. Of 3,417 randomized people, 2,108 were assigned to 2.4 mg cagrilintide plus 2.4 mg semaglutide once weekly, 302 to semaglutide 2.4 mg, 302 to cagrilintide 2.4 mg, and 705 to placebo. | Mean weight change at week 68 was −20.4% with the combination and −3.0% with placebo; estimated difference −17.3 percentage points (95% CI −18.1 to −16.6; p<0.001). Gastrointestinal adverse events occurred in 79.6% and 39.9%, respectively, and were mainly transient and mild-to-moderate. The accessible abstract does not provide the active-comparator hypothesis tests needed for formal superiority claims over either component. |
| REDEFINE 2 | A 68-week, double-blind Phase 3a trial enrolled adults with BMI at least 27 kg/m², type 2 diabetes, and HbA1c of 7–10%. With lifestyle intervention, 1,206 people were randomized 3:1: 904 to 2.4 mg cagrilintide plus 2.4 mg semaglutide once weekly and 302 to placebo. | Mean weight change was −13.7% with the combination and −3.4% with placebo; estimated difference −10.4 percentage points (95% CI −11.2 to −9.5; p<0.001). Gastrointestinal adverse events occurred in 72.5% and 34.4%, respectively, and were mostly transient and mild or moderate. No component-only arm was included, so this trial cannot directly establish superiority over semaglutide or cagrilintide alone. |
Each estimate belongs with its own trial criteria and controls. REDEFINE 1 enrolled adults without diabetes. REDEFINE 2 required type 2 diabetes.
The weight changes come from separate trials. They do not directly compare people with and without diabetes.
Target dose, escalation, and estimands
The current REDEFINE 1 registry describes 16 weeks of dose escalation. The sponsor’s December 2024 topline release reports the highest-dose share at week 68. It was 57.3% of the combination group.
The arm label names both 2.4 mg components. It does not prove that each person received both amounts throughout.
The same sponsor release gives REDEFINE 1 trial-product estimates. The combination was 2.4 mg cagrilintide plus 2.4 mg semaglutide: −22.7%. Semaglutide 2.4 mg gave −16.1%.
Cagrilintide 2.4 mg gave −11.8%. Placebo gave −2.3%. The separate treatment-policy figures follow that same arm order: −20.4%, −14.9%, −11.5%, and −3.0%.
These arms were randomized within one trial. Their results are therefore direct arm observations. Lead the benefit summary with the peer-reviewed treatment-policy comparison against placebo.
Keep each sponsor-only figure labeled by source and estimand. It cannot replace the peer-reviewed result. Nor is it formal hypothesis testing against an active drug.
REDEFINE 4 direct comparison with tirzepatide
The REDEFINE 4 registry describes an open-label Phase 3 trial. Adults had to be age 18 or older. They needed BMI of at least 30 kg/m².
Type 1 and type 2 diabetes were excluded. So was screening HbA1c of 6.5% or higher. The trial randomized 809 people for up to 84 weeks.
One arm received 2.4 mg cagrilintide plus 2.4 mg semaglutide once weekly. Its dose escalation lasted 16 weeks. The other received tirzepatide 15 mg once weekly.
Its dose escalation lasted 20 weeks. The registry is Completed and posts no results.
The sponsor’s February 2026 topline release gives two sets of mean weight changes. The efficacy estimand assumed treatment adherence but allowed dose changes. CagriSema gave −23.0%, versus −25.5% with tirzepatide.
The treatment-regimen estimand included effects regardless of adherence. Those figures were −20.2% and −23.6%, in the same order.
REDEFINE 4 did not meet its main noninferiority endpoint. That failed test controls what can be claimed. The figures do not establish noninferiority to tirzepatide.
They do not establish equal or better results either.
A fresh PubMed search for REDEFINE 4 or NCT06131437 returned no record during intake. REDEFINE 4 findings thus remain early company-reported results. They come from the direct randomized comparison.
Bringing in a tirzepatide estimate from another trial would be weaker. It would compare across trials instead.
Participant counts and study status
The peer-reviewed papers report randomized counts. REDEFINE 1 reports 3,417 people. REDEFINE 2 reports 1,206.
Current registry enrollment fields differ:
- REDEFINE 1 remains active but is not recruiting. Its record includes an extension. It lists estimated enrollment of 3,400. The actual primary completion date is October 30, 2024. The estimated overall completion date is October 19, 2026.
- The REDEFINE 2 registry is completed. It lists actual enrollment of 1,200. The paper instead says 1,206 people were randomized.
- REDEFINE 4 is completed. It lists actual enrollment of 809. That matches the sponsor’s randomized count.
None of these three registries posts participant-flow results. Completed means the study ended. It does not count the people who finished. Enrollment and randomization counts cannot be called treatment-completion counts.
They cannot be called follow-up-completion counts either.
Current US regulatory status
The sponsor’s December 18, 2025 announcement reports an FDA New Drug Application. It names 2.4 mg cagrilintide plus 2.4 mg semaglutide once weekly for weight management. It says CagriSema was not then approved in the US or EU.
This establishes what the sponsor reported. It is not an FDA approval action. It gives no public NDA number that this review can independently verify.
FDA describes Drugs@FDA as its approved-product database. We checked its September 4, 2026 data page and 12-table archive. The search found no match, regardless of letter case, for CagriSema, cagrilintide, or cagrilintide-semaglutide.
Exact openFDA searches checked the CagriSema brand and cagrilintide ingredient. Both returned HTTP 404 “No matches found.” Exact DailyMed searches found zero records for CagriSema and cagrilintide.
These current US sources showed no approved CagriSema or cagrilintide product. That does not cancel the reported pending filing. It does not predict an FDA decision.
It does not give the combination a semaglutide approval.
Reader questions
Can the two component amounts be combined into one dose figure?
No. The trial arm named 2.4 mg cagrilintide plus 2.4 mg semaglutide. These are separate component amounts.
They must not be added into one dose.
How much weight did people lose in REDEFINE 1 and 2?
The peer-reviewed results use the treatment-policy estimand. They report mean changes in weight at week 68. REDEFINE 1 enrolled adults without diabetes.
CagriSema gave −20.4%, versus −3.0% with placebo. REDEFINE 2 required type 2 diabetes. Its figures were −13.7% and −3.4%.
These are separate placebo-controlled results. They do not directly compare the two populations.
Why do some CagriSema percentages differ?
The sources use different estimands, or questions for measuring effects. Some results include all people randomly assigned, even if they did not follow treatment. Other results ask what happens when people follow treatment, while allowing dose changes in the plan.
The named methods and sources appear beside each set of figures above.
Was CagriSema noninferior to tirzepatide?
That conclusion was not established. The sponsor said REDEFINE 4 failed its main noninferiority endpoint. It also gave two sets of figures for different estimands.
Neither set can override the failed main test.
Did everyone receive both 2.4 mg components for the full trial?
No. REDEFINE 1 used 16 weeks of dose escalation. It also allowed dose changes.
The sponsor reported the highest-dose share at week 68: 57.3% of the combination group. Target amounts name trial arms. They do not prove each person had continuous exposure.
Is CagriSema approved in the United States?
Current US approval and label sources were checked. No approved CagriSema or cagrilintide product was found. The sponsor announced an NDA filing in December 2025.
A filing announcement is not an FDA approval decision.
Can the trial escalation be used as a personal schedule?
No. These are controlled research protocols. They allowed dose changes.
This review found no approved CagriSema label or plan for raising the dose.