CagriSema vs Retatrutide: Which Wins on Weight Loss in 2026?

On the raw numbers, retatrutide is ahead: 28.3% mean weight loss at 12 mg over 80 weeks in the phase 3 TRIUMPH-1 trial, against 22.7% for CagriSema over 68 weeks in REDEFINE 1.^[1][2] Those figures come from different trials, durations, estimands and evidence tiers, so the gap between them measures nothing. No head-to-head trial of retatrutide against CagriSema has ever been run or registered. Here is what each drug proved, and how to read the two datasets side by side without inventing a result nobody produced.

The Short Answer, and Why It Comes With Conditions

Forced to pick one, it is retatrutide, because its best phase 3 figure sits roughly six percentage points above CagriSema's. That answer survives about thirty seconds of scrutiny. The two programmes ran on separate clocks, in separate populations, using separate conventions for handling people who quit treatment. Retatrutide's advantage is real in that the numbers are what they are, and unproven in that no experiment has put the two molecules in the same room.

The Headline Numbers, With the Fine Print Attached

Every phase 3 weight-loss result either drug has reported, with its conditions:

Read that as six separate experiments, not one leaderboard. The only two rows sharing a duration are REDEFINE 1 and TRIUMPH-4, and TRIUMPH-4 enrolled people with knee osteoarthritis.

22.7% and 20.4% Are the Same Trial: The Estimand Problem

CagriSema is quoted at both 22.7% and 20.4%, and those are occasionally treated as two studies. They are one study analysed two ways. The trial product estimand asks what happens if everyone takes the drug as directed for the full 68 weeks: 22.7% against 2.3% placebo. The treatment policy estimand asks what happens to everyone randomised, whether or not they stayed on drug: 20.4% against 3.0%.^[2][10]

Lilly uses the same two lenses under different labels. TRIUMPH-1's efficacy estimand gave 28.3% at 12 mg against 2.2% placebo; treatment regimen gave 25.0% against 3.9%.^[1] The rule is to match the lens: trial product against efficacy is 22.7% versus 28.3%, treatment policy against treatment regimen is 20.4% versus 25.0%. Quoting retatrutide's 28.3% against CagriSema's 20.4% inflates the gap by roughly three points before any biology enters.

REDEFINE 1 also ran both components as standalone arms, the cleanest look at what the amylin analogue contributes. Trial product estimand at 68 weeks: CagriSema 22.7%, semaglutide 2.4 mg alone 16.1%, cagrilintide 2.4 mg alone 11.8%, placebo 2.3%.^[10] The amylin component is worth about 6.6 points.

Five Reasons This Is Not an Apples-to-Apples Comparison

• Duration. REDEFINE 1 stopped at 68 weeks; TRIUMPH-1 ran to 80. Twelve extra weeks on a still-descending curve is not free.
• Population. REDEFINE 1 excluded any diabetes history and an HbA1c of 6.5% or above, requiring a BMI of 30 or more, or 27 with a weight-related complication.^[12] TRIUMPH-3 enrolled BMI 35 or above with cardiovascular disease; TRIUMPH-4 enrolled knee osteoarthritis.
• Estimand. Worth two to three percentage points on its own.
• Phase. The 24.2% still widely quoted is the phase 2 result at 12 mg over 48 weeks (n=338), alongside 22.8% at 8 mg, 17.1% at 4 mg, 8.7% at 1 mg and 2.1% placebo.^[6] TRIUMPH-1 superseded it.
• Peer review. One programme published its results; the other announced them.

Mechanism: Amylin Plus GLP-1 Versus GIP, GLP-1 and Glucagon

CagriSema is two molecules. Cagrilintide is a long-acting acylated amylin analogue acting as a non-selective agonist at all three amylin receptors (AMY1R, AMY2R, AMY3R) and at the calcitonin receptor; structural work in Nature Communications shows it binds in an amylin-like mode while inducing distinct conformational dynamics at calcitonin-family receptors.^[13] Paired with semaglutide it recruits a satiety pathway separate from GLP-1, which is why the combination beat either component alone in the same trial. Our cagrilintide pharmacology guide covers the receptor biology.

Retatrutide is one molecule doing three jobs: a single peptide conjugated to a fatty diacid moiety that activates the GIP, GLP-1 and glucagon receptors.^[14] Glucagon agonism is the differentiator: it may reduce liver fat by stimulating hepatic fatty acid oxidation and reducing hepatic lipogenesis, and in preclinical models retatrutide raised energy expenditure beyond calorie-intake-matched controls.^[15] That pathway is also the most plausible source of the dose-dependent heart-rate increases in phase 2, which peaked at week 24.^[6] One drug adds a second appetite pathway; the other adds energy expenditure alongside two incretin pathways.

Tolerability: The Closest Thing to a Fair Read (Both at 68 Weeks)

Gastrointestinal events hit 79.6% of the CagriSema group in REDEFINE 1 versus 39.9% on placebo, mostly transient and mild to moderate, and 6.0% discontinued for an adverse event versus 3.7%.^[2][16]

TRIUMPH-1 at 12 mg reported nausea 42.4%, diarrhea 32.0%, constipation 26.1% and vomiting 25.3% (placebo 14.8%, 13.5%, 10.9%, 4.8%). Discontinuation for adverse events was dose-dependent: 11.3% at 12 mg, 6.9% at 9 mg, 4.1% at 4 mg, against 4.9% placebo.^[1] Across TRIUMPH-2 and TRIUMPH-3 the range was 3.8% to 13.5% versus 4.8% to 4.9% placebo.^[9]

The one duration-matched comparison, REDEFINE 1 against TRIUMPH-4 at 68 weeks each, does not favour retatrutide. TRIUMPH-4's 28.7% at 12 mg came with an 18.2% discontinuation rate against 4.0% placebo, roughly three times CagriSema's 6.0%.^[11] The populations differ, so this is the closest read available rather than a clean one.

The Dysesthesia Signal Nobody Was Expecting

Dysesthesia, an abnormal or unpleasant skin sensation, has no counterpart in the CagriSema data. TRIUMPH-1 reported it in 12.5% of the 12 mg group against 0.9% placebo; TRIUMPH-4 reported 20.9% against 0.7%.^[1][11][17] It is a new signal for the class, it scales with dose, and it explains much of the discontinuation gap.

Dosing Burden: One Fixed Dose Versus a Ladder to 12 mg

Both are once-weekly subcutaneous injections, but the regimens differ in shape. CagriSema is a fixed-dose co-formulation of two molecules in one pen, escalated over 16 weeks to a 2.4/2.4 mg target and held there for the remaining 52 weeks.^[12] Retatrutide is one molecule escalated every four weeks toward 4, 9 or 12 mg, so it carries a dose-selection decision CagriSema does not.^[1]

That last row is the least-discussed finding in REDEFINE 1: the amylin analogue made the top dose measurably harder to stay on.^[10] For the retatrutide ladder, our retatrutide dosage chart covers the trial doses. The aggressive gray-market ramps circulating online are community convention and appear in no protocol; phase 2 went the other way, using a 2 mg start rather than 4 mg to blunt gastrointestinal effects.^[6]

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How They Perform in Type 2 Diabetes

The gap widens here. REDEFINE 2 put CagriSema at 13.7% against 3.4% placebo over 68 weeks under treatment policy.^[7] TRIUMPH-2 put retatrutide 12 mg at 20.8% against 4.0% over 80 weeks, with A1C reductions up to 1.6%.^[9] The duration and estimand caveats still apply, but a roughly seven-point spread is harder to explain with methodology than the six-point spread in the diabetes-free trials.

The Only Legitimate Bridge: Tirzepatide as Common Comparator

With no direct trial, the defensible way to connect the programmes is a drug both have been or will be tested against: tirzepatide.

CagriSema has already made that run, and lost. REDEFINE 4 was an open-label head-to-head in 809 adults with obesity over 84 weeks, mean baseline weight 114.2 kg. CagriSema produced 23.0% against tirzepatide 15 mg at 25.5% (efficacy estimand), and 20.2% against 23.6% (treatment regimen). The primary endpoint of non-inferiority was not met.^[4]

Retatrutide's equivalent is TRIUMPH-5 (NCT06662383), a double-blind phase 3 trial against tirzepatide in 800 adults with obesity, running about 89 weeks, active and not recruiting, with primary completion listed for November 2026 and study completion for December 2026.^[5] That readout, not cross-trial arithmetic, settles the question.

Regulatory Status: One Is Filed, One Is Not

Novo Nordisk filed a CagriSema NDA on 18 December 2025 on the strength of REDEFINE 1 and 2, with a decision expected during 2026; the filing release states plainly that CagriSema is not approved in the US or EU.^[8] Lilly plans a retatrutide BLA in Q1 2027.^[9] Neither is approved anywhere as of August 2026, putting CagriSema roughly a year ahead. Our CagriSema status page tracks that filing.

Evidence Tier: NEJM Versus Press Release

This asymmetry matters more than any single percentage point. CagriSema's headline numbers are peer-reviewed: REDEFINE 1 and 2 are both in the New England Journal of Medicine, with both estimands, safety tables and arm-by-arm results open to inspection.^[2][7]

Retatrutide's phase 3 numbers are not published anywhere peer-reviewed. A PubMed search for TRIUMPH-1 returns only a design-and-rationale paper covering the four-trial programme and its more than 5,800 participants.^[14] Every retatrutide phase 3 figure here, 28.3%, 30.3%, 28.7%, 22.6% and 20.8%, comes from an Eli Lilly press release. Company toplines are usually accurate on direction, but they are selected summaries. Retatrutide's peer-reviewed record is still the 2023 phase 2 trial.^[6]

Which One Should You Actually Care About

For the largest demonstrated phase 3 weight loss, retatrutide: 28.3% at 12 mg over 80 weeks, with 62.5% reaching 25% or more, 45.3% reaching 30% or more and 27.2% reaching 35% or more, against placebo rates of 2.2%, 0.5% and 0.3%. A pre-specified blinded extension in 532 participants with baseline BMI 35 or above reached 30.3% at 104 weeks.^[1]

For results delivered with fewer dropouts, the picture flips at the duration-matched comparison: CagriSema's 6.0% discontinuation over 68 weeks against TRIUMPH-4's 18.2%.^[2][11] For whichever you might be prescribed first, it is CagriSema, by about a year.^[8][9]

One point for anyone browsing the research-chemical market: buying research-grade cagrilintide and injecting it alongside semaglutide does not reproduce CagriSema, whose co-formulation pharmacokinetics were never tested as two separate injections, so the REDEFINE numbers do not transfer. Our retatrutide and cagrilintide stack guide covers the same problem from the other direction, and our cagrilintide buying guide covers sourcing and purity.

What Would Change This Answer

• TRIUMPH-5 reading out (December 2026), which paired with REDEFINE 4 gives both drugs a measured result against the same comparator.^[5]
• Peer-reviewed TRIUMPH publications, which would put retatrutide's phase 3 data at CagriSema's evidentiary level.
• An FDA decision on CagriSema, expected during 2026.^[8]
• A registered head-to-head, which would make every cross-trial estimate here obsolete.^[3]

Frequently Asked Questions

References

1. Eli Lilly. TRIUMPH-1 topline, 21 May 2026.
2. REDEFINE 1. N Engl J Med (PMID 40544433, NCT05567796).
3. ClinicalTrials.gov API v2. Retatrutide intervention listing.
4. Novo Nordisk. REDEFINE 4 versus tirzepatide, 23 Feb 2026.
5. ClinicalTrials.gov NCT06662383. TRIUMPH-5.
6. Jastreboff AM, et al. Retatrutide phase 2. N Engl J Med (PMID 37366315).
7. REDEFINE 2. N Engl J Med (PMID 40544432, NCT05394519).
8. Novo Nordisk files CagriSema NDA, 18 Dec 2025.
9. Eli Lilly. TRIUMPH-2 and TRIUMPH-3 topline, 23 July 2026.
10. Novo Nordisk. REDEFINE 1 arm-by-arm results and dose attainment.
11. Eli Lilly. TRIUMPH-4 results (NCT05869903), 11 Dec 2025.
12. ClinicalTrials.gov NCT05567796. REDEFINE 1 protocol record.
13. Cao J, et al. Cagrilintide binding to calcitonin and amylin receptors. Nat Commun. 2025 (PMID 40204768).
14. TRIUMPH programme design and rationale. Diabetes Obes Metab (PMID 41090431).
15. Retatrutide for MASLD, phase 2a (PMC11271400).
16. Novo Nordisk. CagriSema 22.7% in REDEFINE 1, published in NEJM.
17. BioSpace. Retatrutide dysesthesia safety signal.