Retatrutide vs CagriSema: The Short Version

Retatrutide is one molecule acting on three receptors. CagriSema is two molecules — semaglutide and cagrilintide — in a single weekly injection. Retatrutide produced more weight loss in Phase 3: 28.3% against 22.7% if each drug is taken as intended, and 25.0% against 20.4% across everyone randomized. The gap is real, and it is roughly half the size usually quoted. Neither drug is approved.

The most consequential CagriSema results of 2026 are not in that table. CagriSema was tested directly against tirzepatide, an approved drug, twice: at full doses in people with obesity it missed its endpoint, and at lower doses in people with type 2 diabetes it produced more weight loss. Both trials are covered below, once the figures above are on the same footing.

Why Retatrutide's Lead Looks Bigger Than It Is

The figure in circulation is retatrutide's 28.7% against CagriSema's 20.4%. Those two numbers come from different trials, in different populations, reported on different bases.

Obesity trials publish two headline results. The efficacy estimand (CagriSema's developer calls its version the trial-product estimand) estimates the effect if everyone had taken the drug as intended. The treatment-regimen estimand (treatment policy, in CagriSema's reporting) includes everyone randomized, whether or not they stayed on the drug or reached the top dose. For the drug arms, the first number is the larger one.

28.7% is an efficacy figure. 20.4% is a treatment-policy figure. The comparison sets one company's optimistic number against the other's conservative one, and reads the difference as pharmacology.

Matched properly, retatrutide's advantage is 5.6 percentage points if each drug is taken as intended (28.3% against 22.7%) and 4.6 points across everyone randomized (25.0% against 20.4%). Pair CagriSema with TRIUMPH-4 instead and the same two comparisons give 6.0 and 3.3 points. Adjust each figure for its own trial's placebo arm and the as-intended gap is 5.7 points.

Whichever way it is cut, the answer sits between three and six points. Not 8.3.

Which Retatrutide Trial Belongs Next to REDEFINE-1

TRIUMPH-4's 28.7% is a real Phase 3 result, but it comes from 445 adults with obesity and knee osteoarthritis over 68 weeks. TRIUMPH-1 enrolled 2,339 adults with obesity and without diabetes over 80 weeks — a population and a scale comparable to REDEFINE-1's 3,417. TRIUMPH-1 is the trial built for this comparison.

Neither pairing is clean. TRIUMPH-1 ran twelve weeks longer than REDEFINE-1, which favors retatrutide. TRIUMPH-4 matches REDEFINE-1's 68 weeks, but with 445 participants against 3,417, in a population selected for knee osteoarthritis. And the two trials started from different average weights — 112.7 kg in TRIUMPH-1, 106.9 kg in REDEFINE-1 — so equal percentages are not equal pounds. Every cross-trial comparison on this page, including ours, is an inference rather than a measurement.

What REDEFINE-1 Showed About CagriSema Itself

REDEFINE-1 was not simply CagriSema against placebo. It ran four arms, and the three smaller ones are the more interesting part. Under the as-intended estimand, CagriSema produced 22.7%, semaglutide alone 16.1%, cagrilintide alone 11.8% and placebo 2.3%.

So adding cagrilintide to semaglutide was worth about 6.6 points — measured inside a single trial, with the same patients, the same protocol and the same estimand. That internal gap is larger than the 5.6 points separating CagriSema from retatrutide across two trials, which is worth holding in mind before treating any cross-trial difference as settled.

REDEFINE-1 also allowed investigators to reduce the dose when participants could not tolerate it. At week 68, 57.3% were on the full 2.4 mg/2.4 mg dose, according to the developer's topline announcement. The distance between a drug's two estimands (2.3 points for CagriSema, 3.3 for retatrutide in TRIUMPH-1) reflects, in part, what dose reductions, dropouts and switching to something else cost it.

CagriSema vs Tirzepatide: Two Head-to-Head Trials

Two CagriSema comparisons are not inferences. REDEFINE 4 enrolled 809 adults with obesity and at least one weight-related complication, and ran full-dose CagriSema against tirzepatide 15 mg, the highest approved dose, for 84 weeks, open-label. REIMAGINE 5 ran lower doses of both, CagriSema 1.0 mg/1.0 mg against tirzepatide 5 mg, for 60 weeks in adults with type 2 diabetes.

REDEFINE 4 did not meet its primary endpoint of demonstrating non-inferiority to tirzepatide; the result was announced on February 23, 2026. REIMAGINE 5, announced on September 21, 2026, went the other way: CagriSema produced 12.4% weight loss against 9.1% on tirzepatide, a statistically superior result, and lowered HbA1c by 1.71 points against 1.67, which met the test for non-inferiority. Both figures are on the as-intended basis, and the release did not give the number of participants or adverse event rates.

Read together, the two trials say that CagriSema did not match tirzepatide at their highest doses, and beat it at lower ones in type 2 diabetes. These are measured comparisons, which no retatrutide comparison with CagriSema is.

It also frames the retatrutide question. Retatrutide's own head-to-head trial against tirzepatide, TRIUMPH-5, has not reported results, as far as we found. Until it does, its 28.3% in TRIUMPH-1 running ahead of the 25.5% tirzepatide produced in REDEFINE 4 is another cross-trial inference (see retatrutide vs tirzepatide vs semaglutide).

How Many People Lost 25% or More

Averages hide the tails, so the more useful question is how many people cleared a given threshold. Under the as-intended estimand, 62.5% of those on retatrutide 12 mg in TRIUMPH-1 lost at least a quarter of their body weight and 45.3% lost at least 30%. In REDEFINE-1, 40.4% of CagriSema participants lost at least 25% and 23.1% lost at least 30%. Same estimand class, 80 weeks against 68.

Those are the two thresholds both developers' announcements give on the same as-intended basis. REDEFINE-1 also reported 97.6% at 5% or more and 60.2% at 20% or more. The TRIUMPH-1 announcement gave nothing below 25%, but the full TRIUMPH-1 paper, published in September 2026, reports every threshold from 5% to 35%; its main table counts everyone randomized, with 94.0% of the 12 mg group losing at least 5% and 66.8% at least 20%. A comparison at the lower thresholds has to use the same estimand for both drugs.

How Retatrutide and CagriSema Work

Retatrutide acts on GLP-1, GIP and glucagon receptors at once. GLP-1 reduces appetite and slows gastric emptying; GIP enhances insulin release. The glucagon receptor is the addition: the developer's medical information describes it as intended to help maintain energy expenditure during weight loss, so retatrutide may act on energy burned as well as energy eaten.

CagriSema pairs semaglutide, an established GLP-1 agonist, with cagrilintide, a long-acting analog of amylin. Amylin is a hormone co-secreted with insulin that signals satiety through its own receptor system. The design therefore adds a second appetite pathway rather than a metabolic one, which is a different bet from retatrutide's.

Half of CagriSema is already an approved medicine with years of post-marketing data behind it. Retatrutide is entirely new.

Has Retatrutide Been Studied With Cagrilintide?

No. As far as we found, no published trial, and no trial announced by either developer, has tested retatrutide together with cagrilintide. The two come from competing companies. Cagrilintide has been studied on its own and with semaglutide, which is what CagriSema is; retatrutide's Phase 3 trials tested it on its own.

The pairing searched for as "reta and cagri" comes from online sellers that market the two as a "stack." Those products are not made or supplied by either developer, and nothing is known about the effects or safety of combining the two compounds: no trial has measured whether the weight loss adds up, whether gastrointestinal side effects, already the most common with each drug, get worse together, or what doses would be involved. Adding an amylin analog to a GLP-1 drug is an active research area, and CagriSema is one result of it, but what one pairing does says nothing reliable about another.

Side Effects: Retatrutide vs CagriSema

The full list for retatrutide is in retatrutide side effects.

Where the two companies reported the same symptom, the result runs against what the weight-loss figures would suggest. Nausea was more common on CagriSema — 55% in REDEFINE-1 against 42.4% on retatrutide 12 mg — with near-identical placebo arms, 12.6% and 14.8%. Vomiting was a dead heat, 26.1% against 25.3%, and constipation close, 30.7% against 26.1%. CagriSema's developer also published a combined gastrointestinal total of 79.6%, which retatrutide's announcement did not; retatrutide's announcement gave diarrhea, which CagriSema's did not.

What does compare cleanly is discontinuation. In TRIUMPH-1, 11.2% of participants on 12 mg stopped because of side effects, against 4.6% on placebo, according to the published paper. In REDEFINE-1, 5.9% stopped because of adverse events, against 3.7% on placebo, according to the developer's announcement of the published results. Retatrutide's rate is roughly double CagriSema's, and more than double its own placebo arm.

Dysesthesia

Dysesthesia is an altered sense of touch — tingling, burning, or ordinary contact registering as unpleasant. In TRIUMPH-1, 12.5% of participants on 12 mg reported it against 0.9% on placebo; in TRIUMPH-4, 20.9% against 0.7%. The company said the events were generally mild to moderate, and for TRIUMPH-4 that they rarely led to discontinuation.

It is often described as retatrutide's alone. It is not. Semaglutide — the other half of CagriSema — lists it on its US label: 2% against 1% on placebo in the three trials pooled for the 2.4 mg dose, and 6% on 2.4 mg and 22% on the 7.2 mg dose approved in 2026, against 0.3% on placebo, in the later trials that tested the higher dose. Tirzepatide's label lists it at 0.4% on 15 mg, against 0.1% on placebo. On these figures, retatrutide 12 mg in TRIUMPH-1 had a higher rate than semaglutide 2.4 mg, the dose CagriSema contains, on either measure — in comparisons across different trials that may not count exactly the same terms.

Dosing: Neither Drug Has an Approved Dose

Neither drug has an FDA label, so neither has an approved starting dose, escalation schedule or maximum. What exists in both cases is a trial protocol: a schedule used on a screened population, under monitoring, with clinicians who could pause or lower the dose the moment something went wrong.

TRIUMPH-1 studied maintenance doses of 4 mg, 9 mg and 12 mg. REDEFINE-1 targeted 2.4 mg of each component, with reduction permitted for tolerability — and, as above, not quite three in five participants were on the full dose at the end. A protocol records what happened under those conditions. It is not instructions, and it does not transfer to a vial bought online.

That last point is worth stating plainly. Products sold on the internet under either name are not sold or supplied by either developer, and are not the compounds these trials studied. They are not made under pharmaceutical manufacturing oversight, their contents are not verified, and nobody is monitoring the person taking them. Every figure on this page describes a supervised clinical trial and none of them describe anything bought from a website.

FDA Status: CagriSema Filed, Retatrutide Not Yet

CagriSema was submitted to the FDA on December 18, 2025, for weight management. It remains under review; in September 2026 its developer said a decision is expected in the fourth quarter of 2026. The indication sought is weight management, not diabetes, and its developer has said it will approach regulators separately about a type 2 diabetes pathway. In February 2026 it reported REIMAGINE 2, in which CagriSema produced 14.2% weight loss and a 1.91-point HbA1c reduction in adults with type 2 diabetes.

Retatrutide has not been submitted. The last of its four core TRIUMPH trials read out in July 2026, and the company plans to file in the first quarter of 2027. A filing starts a review rather than a countdown to approval: the FDA can accept or refuse to file, request more data, or approve with restrictions.

The two filings are about a year apart, so CagriSema is on course to be decided first. Any launch date quoted for retatrutide is an estimate.

Cost: Why There Is No Price Yet

Neither drug has a price, because neither is sold. Published "expected" prices for unapproved medicines are guesses, and they have been wrong in this category before: the approved drugs in this class now sell direct from their manufacturers at a fraction of their list prices, and the Medicare GLP-1 Bridge demonstration — running July 1, 2026 through December 31, 2027 — puts eligible beneficiaries at $50 a month. What either new drug will cost, and what insurers will do about it, is not knowable yet (see how much retatrutide may cost).

What the Data Supports

Retatrutide produced more weight loss on every matched comparison, and considerably more at the higher thresholds — 45.3% of participants at 12 mg lost at least 30% of their body weight, against 23.1% on CagriSema. It also had roughly twice the discontinuation rate, reported dysesthesia at a higher rate than semaglutide 2.4 mg's label figures, and is the further of the two from an FDA decision.

CagriSema is closer to approval and half-built from a medicine with an established safety record. Fewer people stopped taking it, 5.9% against 11.2% — though more of them were nauseated, 55% against 42.4%. It is also the only one of the two with head-to-head results against an approved drug: behind tirzepatide at full doses, ahead of it at lower doses in type 2 diabetes.

Neither can be prescribed. Semaglutide, tirzepatide and orforglipron are approved.

Retatrutide vs CagriSema in Summary

Retatrutide leads CagriSema by three to six percentage points depending on which trials and which estimands are paired, not the 8.3 points that result from setting one developer's best-case figure against the other's all-comers figure. The ordering is not in dispute; the distance is smaller than advertised, and the trials it rests on were never designed to be compared.

The 2026 results that changed the picture were not retatrutide trials at all. In REDEFINE 4, CagriSema was measured against tirzepatide at full doses and did not meet its endpoint; in REIMAGINE 5, at lower doses in type 2 diabetes, it produced more weight loss. No trial has tested retatrutide together with cagrilintide, as far as we found.

The full TRIUMPH-1 paper, published in the New England Journal of Medicine in September 2026, confirmed the 28.3% and 25.0% figures used here.

Sources

• Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2025. (REDEFINE 1 — both estimands, responder rates, adverse events, dose attainment.)
• Novo Nordisk. CagriSema 2.4 mg/2.4 mg demonstrated 22.7% mean weight reduction in adults with overweight or obesity in REDEFINE 1, published in NEJM. 2025.
• Novo 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. February 23, 2026.
• Novo Nordisk. Novo's CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial. September 21, 2026.
• Novo Nordisk. CagriSema demonstrated superior HbA1c reduction of 1.91%-points and weight loss of 14.2% in adults with type 2 diabetes in the REIMAGINE 2 trial. February 2, 2026.
• Novo Nordisk. Novo Nordisk files for FDA approval of CagriSema for weight management. December 18, 2025.
• Eli Lilly. Retatrutide delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1). May 21, 2026.
• Eli Lilly. Retatrutide delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain (TRIUMPH-4). December 11, 2025.
• Eli Lilly. Retatrutide successful in two additional Phase 3 obesity trials (TRIUMPH-2, TRIUMPH-3). July 23, 2026.
• Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. Published September 29, 2026. DOI: 10.1056/NEJMoa2604169. (TRIUMPH-1)
• Novo Nordisk. Wegovy (semaglutide) US prescribing information, section 6.1. Revised 2026.
• Eli Lilly. US prescribing information for tirzepatide for weight reduction, section 6.1. Revised August 2026.
• Lilly Medical. What is the mechanism of action of retatrutide?
• Centers for Medicare & Medicaid Services. Medicare GLP-1 Bridge: GLP-1 Drugs for $50 a Month. 2026.

Medical Disclaimer: This article is for informational purposes only and is not medical advice. Retatrutide and CagriSema are investigational and neither is approved by the FDA for any use. Neither is available by prescription, and products sold online under their names are not sold or supplied by Lilly or Novo Nordisk. Nothing here is a recommendation to use, seek out, combine or avoid any medication.