CagriSema vs Tirzepatide: Trial Data Compared

Key takeaways

• At full doses, tirzepatide won. In the open-label REDEFINE 4 trial (809 adults with obesity, 84 weeks), weight loss was 20.2% with CagriSema 2.4 mg/2.4 mg versus 23.6% with tirzepatide 15 mg counting everyone, and 23.0% versus 25.5% in people who adhered; CagriSema failed to show it was not worse.
• In type 2 diabetes the picture is mixed: CagriSema matched tirzepatide 15 mg on weight (15.2% versus 15.8%) but not on HbA1c (1.9 versus 2.2 points), and at lower doses CagriSema 1.0 mg/1.0 mg beat tirzepatide 5 mg on weight (12.4% versus 9.1%).
• All three head-to-head results are company-reported toplines from open-label trials; none had been peer-reviewed by October 10, 2026.
• In separate placebo trials the two look alike (20.4% at 68 weeks for CagriSema, 20.9% at 72 weeks for tirzepatide 15 mg), but comparisons across trials are unreliable. CagriSema's nausea and vomiting rates look higher; dropouts for side effects look similar.
• Only tirzepatide can be prescribed: Zepbound costs $299 to $449 a month for cash. CagriSema awaits an FDA decision Novo expects in the fourth quarter of 2026.

Tirzepatide comes out ahead on the data that exist. In the only obesity trial that gave both drugs at full dose, tirzepatide 15 mg removed about three percentage points more body weight than CagriSema 2.4 mg/2.4 mg over 84 weeks, and in type 2 diabetes it lowered blood sugar more. CagriSema won only against tirzepatide's lowest maintenance dose. Our cagrilintide and CagriSema hub explains the drug and its regulatory status, and cagrilintide dosage lists the doses its trials used. Below, every number is labeled with its trial and how it was counted.

The head-to-head trials

Sources: REDEFINE 4 (Novo Nordisk, February 2026); REIMAGINE 4 (Novo Nordisk, August 2026); REIMAGINE 5 (Novo Nordisk, September 2026); enrollment and design from the registry records for REDEFINE 4, REIMAGINE 4 and REIMAGINE 5.

Four things shape how far these results go.

1. They are toplines. All three come from company announcements. Novo has not released adverse-event rates or discontinuations for any of them, and none had appeared in a journal by October 10, 2026.
2. They are open-label. Participants knew which drug they were taking. That matters most for side effects and for decisions to stop, less for a weighed number.
3. 'Counting everyone' and 'if adherent' are different numbers. The treatment-regimen estimand includes people who stopped or switched; the efficacy estimand models what happens if everyone keeps taking the drug. Compare like with like: in REDEFINE 4 the gap was 3.4 points on the first and 2.5 on the second.
4. REIMAGINE 5 asked a narrow question. It set a middle CagriSema dose against tirzepatide 5 mg, the lowest maintenance dose on tirzepatide's label. In SURMOUNT-1, 5 mg produced 15.0% weight loss against 20.9% at 15 mg (Jastreboff 2022), so beating it says little about the top doses.

What the placebo trials show, side by side

Sources: (Garvey 2025) (Jastreboff 2022) (Nong 2026). In type 2 diabetes, use the REIMAGINE 4 and 5 results above rather than setting the separate diabetes trials side by side.

Read this way, the two drugs look nearly identical, and a 2026 BMJ network meta-analysis of 262 trials put them within a tenth of a point of each other at one year (Nong 2026). The head-to-head trial is the stronger evidence, and it favored tirzepatide. Why the direct and indirect comparisons differ is not known: the populations, the length (84 weeks against 68 to 72) and the open-label design all differ, and an indirect comparison cannot separate those from the drugs themselves.

Side effects and dropouts

No head-to-head safety numbers have been published, so the only comparison available sets each drug against its own placebo group.

Sources: (Novo Nordisk, December 2025) (Zepbound label).

The pattern, not the exact numbers, is what to take away: CagriSema's gastrointestinal effects ran higher than Zepbound's in their respective trials, and Novo described them as mostly mild to moderate and fading over time, consistent with the GLP-1 class (Novo Nordisk, February 2026). The BMJ meta-analysis placed CagriSema among the drugs with the most discontinuations for adverse events and found more fatigue (a risk ratio of 3.2, about 92 more people per 1,000 a year), while tirzepatide was among those that increased gastrointestinal events most (Nong 2026). The serious warnings tirzepatide carries, from the thyroid C-cell boxed warning to pancreatitis and gallbladder disease, are class warnings CagriSema's semaglutide component shares; our GLP-1 side effects guide covers them.

How they work and how they are dosed

Tirzepatide is one molecule that activates two receptors, GIP and GLP-1. CagriSema is two molecules given together in one weekly injection: semaglutide for the GLP-1 receptor and cagrilintide, a long-acting amylin analog, for amylin and calcitonin receptors.

Tirzepatide's label starts at 2.5 mg weekly for four weeks, then 5 mg, then 2.5 mg steps no sooner than every four weeks to a maintenance dose of 5, 10 or 15 mg (Zepbound label); the full schedule is in our tirzepatide dosage chart. CagriSema has no label. In REDEFINE 4 it was escalated over 16 weeks to 2.4 mg/2.4 mg and tirzepatide over 20 weeks to 15 mg. Those are studied doses, not a protocol, and only tirzepatide has a prescribable form. If you are on a compounded tirzepatide vial, the units for your labeled concentration are worked out in our peptide calculator.

Availability and cost in October 2026

Tirzepatide is approved as Zepbound for weight management and obstructive sleep apnea, and as Mounjaro for type 2 diabetes. Zepbound costs $299 at 2.5 mg, $399 at 5 mg and $449 at 7.5 to 15 mg a month for cash through Lilly's self-pay program, against a list price of about $1,086; compounded tirzepatide runs $180 to $300 but is legal only for a documented individual need (tirzepatide cost guide).

CagriSema is not approved anywhere. Novo filed it with FDA on December 18, 2025, based on REDEFINE 1 and 2, and expects a decision in the fourth quarter of 2026 (Novo Nordisk, September 2026). No price has been announced. No pharmacy may compound cagrilintide, and vials sold online are unapproved drugs; the legal tracker has the details.

Which should you choose

• You need treatment now. Tirzepatide, or semaglutide; CagriSema is not available. Our Zepbound vs Wegovy comparison covers that choice.
• Maximum weight loss is the goal. Tirzepatide 15 mg did better at full dose in the only obesity head-to-head.
• Type 2 diabetes, with HbA1c the priority. Tirzepatide 15 mg lowered HbA1c more in REIMAGINE 4.
• You do well on tirzepatide. No trial supports switching.
• If CagriSema is approved. It becomes one more option to discuss with a clinician, for example when a plan covers it and not tirzepatide. No trial has tested it in people who responded poorly to tirzepatide, it has no head-to-head advantage at full dose, and its gastrointestinal effects look heavier.

Bottom line

On the evidence as of October 10, 2026, tirzepatide is the stronger drug at full dose: 23.6% versus 20.2% weight loss counting everyone in REDEFINE 4, and a larger HbA1c drop in REIMAGINE 4. CagriSema is close behind, beat tirzepatide's lowest dose, and adds a new mechanism, but all of the direct comparisons are open-label company toplines, and it cannot be prescribed until FDA acts. For a decision this month, the comparison is not CagriSema against tirzepatide; it is tirzepatide against the other approved option.

Frequently asked questions

+−Is CagriSema better than tirzepatide?

Not at full dose, on the evidence so far. In the open-label REDEFINE 4 trial in 809 adults with obesity, CagriSema 2.4 mg/2.4 mg produced 20.2% weight loss at 84 weeks against 23.6% for tirzepatide 15 mg, counting everyone, and failed to show it was not worse. In type 2 diabetes it matched tirzepatide 15 mg on weight but not on HbA1c, and it beat only the 5 mg dose.

+−What were the REDEFINE 4 results?

REDEFINE 4 randomized 809 adults with obesity and at least one weight-related condition to CagriSema 2.4 mg/2.4 mg or tirzepatide 15 mg weekly for 84 weeks, open-label. Weight loss was 20.2% versus 23.6% by the treatment-regimen estimand and 23.0% versus 25.5% in people who adhered. The primary goal, showing CagriSema was non-inferior to tirzepatide, was not met. Novo announced the result on February 23, 2026.

+−Which causes more nausea, CagriSema or tirzepatide?

No head-to-head safety numbers have been published. In separate placebo-controlled data, nausea affected 55% on CagriSema in REDEFINE 1 (12.6% on placebo) and 25% to 29% on Zepbound in its label trials (8% on placebo), while 5.9% stopped CagriSema for side effects versus 4.8% to 6.7% for Zepbound. So nausea looks more common on CagriSema while dropouts look similar, but the trials differed in design, so treat that as a signal rather than a finding.

+−Is CagriSema available in the US?

No. Novo Nordisk filed it with FDA on December 18, 2025 and expects a decision in the fourth quarter of 2026. Until FDA approves it there is no prescription, no pharmacy supply and no price, and vials sold online as cagrilintide or CagriSema are unapproved drugs.

+−Is CagriSema or tirzepatide better for type 2 diabetes?

For blood sugar at full dose, tirzepatide: in REIMAGINE 4, HbA1c fell 2.2 points on tirzepatide 15 mg and 1.9 on CagriSema 2.4 mg/2.4 mg over 68 weeks, and CagriSema missed non-inferiority on HbA1c. Weight loss was similar, 15.8% versus 15.2%. At lower doses, CagriSema 1.0 mg/1.0 mg beat tirzepatide 5 mg on weight (12.4% versus 9.1%) with similar HbA1c.

+−Can I switch from Zepbound to CagriSema?

Not now, because CagriSema is not approved. If it is approved, no trial has yet tested switching between the two, so the decision would rest on your response to tirzepatide, side effects and cost. On the full-dose head-to-head data, someone doing well on tirzepatide has no evidence-based reason to switch.

+−Why did CagriSema win in REIMAGINE 5 but lose in REDEFINE 4?

Different questions. REDEFINE 4 compared both drugs at their top doses in obesity, and tirzepatide 15 mg won. REIMAGINE 5 compared CagriSema 1.0 mg/1.0 mg with tirzepatide 5 mg, the lowest maintenance dose on tirzepatide's label, in type 2 diabetes over 60 weeks. A low dose of one drug beating the lowest dose of another says little about which is stronger at full dose.

Sources

1. NewsNovo Nordisk. CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trial in people with obesity, the primary endpoint was not achieved. Company announcement via BioSpace, February 23, 2026. (2026)
2. SourceNovo Nordisk. Financial report for the period 1 January 2026 to 30 June 2026 (company announcement No 48/2026: REIMAGINE 4 results). Form 6-K filed with the SEC, August 4, 2026. (2026)
3. NewsNovo Nordisk. Novo's CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial (REIMAGINE 5 and REDEFINE 9 topline results; FDA decision expected in Q4 2026). Press release via GlobeNewswire, September 21, 2026. (2026)
4. StudyGarvey WT et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1). N Engl J Med 2025;393:635-47. (2025)
5. StudyJastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med 2022;387:205-16. (2022)
6. LabelEli Lilly. Zepbound (tirzepatide) injection: prescribing information, revised August 2026, sections 2 and 6.1 (DailyMed setid 487cd7e7-434c-4925-99fa-aa80b1cc776b). (2026)
7. NewsNovo Nordisk. Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management (REDEFINE 1 and 2 safety and discontinuation data). Press release via BioSpace, December 18, 2025. (2025)
8. ReviewNong K et al. Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis. BMJ 2026;394:e372161. (2026)