Tirzepatide vs cagrilintide (CagriSema): what the head-to-head trials found

What the head-to-head trials actually compared

The trials compared tirzepatide with CagriSema, not with cagrilintide on its own. This matters for reading every result on this page.

• CagriSema is a fixed-dose combination of cagrilintide with semaglutide, given as a once-weekly injection under the skin. Cagrilintide is an amylin analogue. Semaglutide is a GLP-1 receptor agonist.
• Tirzepatide is never part of CagriSema. In the trials below it is the active comparator.
• Cagrilintide alone has not been tested against tirzepatide in any trial recorded here.

So a CagriSema result reflects cagrilintide and semaglutide working together. It does not tell you how cagrilintide alone compares with tirzepatide.

How tirzepatide is thought to work. The US Zepbound label says GLP-1 is a natural regulator of appetite and calorie intake, and nonclinical studies suggest GIP may add to the regulation of food intake. The label says tirzepatide lowers calorie intake, likely by affecting appetite.

How cagrilintide is thought to work. Natural amylin is a pancreatic hormone that induces satiety. Cagrilintide activates the amylin receptors and the calcitonin receptor. Novo Nordisk describes the two parts of CagriSema as targeting "complementary obesity-related pathways".

The head-to-head trial results

Novo Nordisk has run three trials that compared CagriSema with tirzepatide. All three results are company-reported, not peer reviewed in the sources checked. The tirzepatide doses below are the comparator arms the trials used, not treatment advice.

REIMAGINE 4 figures are as reported for the case in which all people adhered to treatment. Novo Nordisk's words on REDEFINE 4: the trial "did not achieve its primary endpoint of demonstrating non-inferiority on weight loss for CagriSema compared to tirzepatide". On REIMAGINE 4, it said CagriSema "demonstrated non-inferiority versus tirzepatide 15 mg for weight reduction, but not for HbA1c reduction".

Points to keep in mind:

• Open-label. REDEFINE 4 and REIMAGINE 4 were open-label, so participants and staff knew which medicine was given. Whether REIMAGINE 5 was open-label is not recorded in the sources checked.
• Company-reported. All three results come from Novo Nordisk announcements and filings. No peer-reviewed publication of these trials was found in the sources checked.
• A low comparator dose in REIMAGINE 5. It compared a lower dose of CagriSema with tirzepatide 5 mg. Its result does not show how CagriSema compares with tirzepatide at higher doses.
• Different estimands. Novo Nordisk reported REDEFINE 4 using two estimands (efficacy and treatment-regimen), which give different numbers.

Other evidence for each

Outside the head-to-head trials, both have large placebo-controlled trials. These are separate trials, with different people and lengths, so they are not a head-to-head comparison. Results are shown by dose group without dose amounts.

Cagrilintide alone. In a 26-week phase 2 trial of 706 adults without diabetes, mean weight loss was 6.0% to 10.8% across five cagrilintide dose groups, versus 3.0% with placebo. Novo Nordisk reports 11.8% at 68 weeks for the cagrilintide-alone group of REDEFINE 1 (company-reported, not in the peer-reviewed abstract). Neither was compared with tirzepatide.

Heart outcomes. Tirzepatide has a completed heart outcome trial in type 2 diabetes (SURPASS-CVOT), covered on the tirzepatide page. CagriSema's heart outcome trial, REDEFINE 3, has no results yet; Novo Nordisk expects them in the second half of 2027.

Side effects compared

Stomach and gut side effects were the most common with both. In REDEFINE 4, Novo Nordisk said the most common side effects with CagriSema were gastrointestinal. No side-by-side side effect figures from the head-to-head trials are recorded here.

The figures below come from different trials and sources, so a higher number in one column does not show that one causes more of a side effect than the other.

Figures reported by Novo Nordisk come from its releases, not from the peer-reviewed abstracts checked.

Tirzepatide label warnings. The US Zepbound label carries a boxed warning: tirzepatide caused thyroid C-cell tumors in rats, and it is unknown whether it causes them in humans. The label also lists acute pancreatitis, gallbladder disease, acute kidney injury from dehydration, serious allergic reactions and harm to an unborn baby. It says most nausea, vomiting and diarrhea "occurred during dose escalation and decreased over time."

CagriSema. It has no approved label, so there is no official list of warnings or people who should not use it. In REDEFINE 1, gastrointestinal side effects were mainly transient and mild to moderate.

Approval status compared

Tirzepatide is an approved medicine. CagriSema is still under review and has no approval in the sources checked.

On December 18, 2025, Novo Nordisk said "CagriSema is not approved in the US or EU." A submission is a request for review, not an approval.

Cagrilintide outside trials. As of October 1, 2026, the US FDA says cagrilintide cannot be used in compounding under US federal law, is not a component of any FDA-approved drug and "has not been found safe and effective for any condition."

Sport and anti-doping

Neither is named as prohibited on the WADA list, but they sit in different places.

• Tirzepatide is in the WADA 2027 Monitoring Program. USADA says this means it is not prohibited, but labs test for it.
• Cagrilintide is not named on the 2027 Prohibited List and is not in the Monitoring Program. It may be prohibited under class S0, non-approved substances, which covers substances with "no current approval by any governmental regulatory health authority for human therapeutic use", including drugs in clinical development. Whether it falls under S0 is a reading of that definition, not a named listing.

Athletes should check with their national anti-doping organisation before using either.

Legal status in the Philippines

Mounjaro and Mounjaro KwikPen (tirzepatide) are listed as registered prescription drugs in the FDA Philippines Verification Portal (checked October 7, 2026). No FDA Philippines registration record was found for cagrilintide or CagriSema.

Each tirzepatide advisory warned the public against a specific unregistered product with no Certificate of Product Registration.

Prescriptions. Under the Philippine Pharmacy Act (RA 10918, Sections 30 and 33), prescription medicines may be dispensed only with a valid prescription from a physician, dentist or veterinarian, and only through a retail drug outlet licensed by FDA Philippines. They must be dispensed by a registered and licensed pharmacist, except in emergencies when no pharmacist is available (with a report to the supervising pharmacist within 24 hours).

To check any product, search the FDA Philippines verification portal at verification.fda.gov.ph. For more on Philippine rules, see are peptides legal in the Philippines.

How to read this comparison

The head-to-head numbers sit next to each other, but they do not settle which medicine suits a person.

What the trials can tell you.

• How CagriSema and tirzepatide compared on weight and HbA1c in three specific trials, as reported by Novo Nordisk.
• That in REDEFINE 4, non-inferiority of CagriSema to tirzepatide 15 mg on weight loss was not shown.

What they cannot tell you.

• How cagrilintide alone compares with tirzepatide. No such trial exists in the sources checked.
• How CagriSema compares with higher tirzepatide doses in type 2 diabetes beyond REIMAGINE 4, since REIMAGINE 5 used tirzepatide 5 mg.
• Peer-reviewed detail. None of the three trials had been published in a journal in the sources checked.
• How any one person will respond. Trial averages do not predict individual results.

Tirzepatide is an approved medicine with a full label; CagriSema is investigational. Whether any medicine suits you is a decision for a licensed doctor. For background, see semaglutide vs tirzepatide and GLP-1 medicines explained.