Retatrutide vs CagriSema: Weight Loss, Side Effects and Status

CagriSema vs retatrutide comes down to this: retatrutide 12 mg took off more weight in its big obesity trial than CagriSema did in its own, 25.0% of body weight against 20.4%, but the two have never been tested against each other and the trials aren't built the same way. CagriSema is the nearer to the pharmacy. Novo Nordisk filed it with the FDA in December 2025, and retatrutide has not been filed.

CagriSema is a once-weekly injection that combines cagrilintide, a drug that mimics the hormone amylin, with semaglutide, the drug in Wegovy and Ozempic. Retatrutide is Eli Lilly's single molecule that acts on GIP, GLP-1 and glucagon receptors.

Every comparison below sets one trial beside another. Where a number depends on how the trial counted dropouts, we label it.

CagriSema vs retatrutide side by side

Sources: Lilly's TRIUMPH-1 release and the NEJM paper (Jastreboff et al.), the TRIUMPH-2 Lancet paper (Bellido et al.), Novo's December 18, 2025 FDA filing release, and the REDEFINE 1 and 2 reports in NEJM.

How do the two drugs work differently?

Semaglutide copies GLP-1, a gut hormone that tells the brain you're full and slows the stomach. Cagrilintide copies amylin, a different hormone released with insulin. Novo's bet is that two hormone signals beat one, and Novo describes CagriSema as the first injectable GLP-1 and amylin combination if it is approved.

Retatrutide takes another route. It's a single molecule that activates GIP and GLP-1 receptors, like tirzepatide, and adds the glucagon receptor on top.

So one drug brings amylin and the other brings glucagon, and no trial has tried to say which extra signal is worth more.

How much weight do people lose on CagriSema?

In REDEFINE 1, a 68-week trial of 3,417 adults with obesity or overweight and no diabetes, CagriSema 2.4 mg/2.4 mg cut body weight by 20.4% against 3.0% on placebo when everyone randomized is counted (NEJM, Garvey et al.). If everyone had stayed on treatment, Novo reports 22.7% against 2.3%. Novo also says the protocol let investigators keep people on a lower dose when that suited them, which may lower the first number.

With type 2 diabetes the losses are smaller, as they are on every drug in this class. In REDEFINE 2, 1,206 adults with type 2 diabetes lost 13.7% on CagriSema against 3.4% on placebo over 68 weeks (NEJM, Davies et al.).

In February 2026 Novo announced REDEFINE 4, an 84-week open-label trial of 809 adults against tirzepatide 15 mg. CagriSema lost 20.2% and tirzepatide 23.6% when everyone randomized is counted; if everyone had stayed on treatment, it was 23.0% against 25.5%. Novo said the trial did not meet its primary goal of showing CagriSema was not worse than tirzepatide.

Our read: CagriSema is a real weight-loss drug that sits a few points below tirzepatide, and that is the bar retatrutide's own numbers have to be read against.

How much weight do people lose on retatrutide?

In TRIUMPH-1, 2,339 adults without diabetes lost 25.0% of body weight on 12 mg over 80 weeks, counting everyone randomized, against 3.9% on placebo (NEJM, Jastreboff et al.). Lilly's figure if everyone had stayed on treatment is 28.3% against 2.2%. The 9 mg dose lost 23.7% on the same measure. The full set of results is on our retatrutide weight loss results page.

In TRIUMPH-2, adults with obesity and type 2 diabetes lost 18.8% on 12 mg against 5.1% on placebo (The Lancet, Bellido et al.).

Why you can't just subtract the two numbers

Three things differ. Retatrutide's trial ran 80 weeks and CagriSema's 68, and a longer trial gives a drug more time to work. Retatrutide had three dose levels with a 12 mg ceiling, while CagriSema was tested at one dose with room for lower doses. And the placebo groups differed by about a point on the same measure (3.9% against 3.0%), a reminder that these are different people at different sites.

The only fair test is one trial with both drugs, which doesn't exist. The nearest thing is a shared comparator: CagriSema has met tirzepatide in REDEFINE 4, and retatrutide meets tirzepatide in TRIUMPH-5, which has not reported (ClinicalTrials.gov lists primary completion as November 2026, an estimate). That is the result to wait for, and our retatrutide vs tirzepatide page will carry it.

Side effects and stopping rates

Both drugs bring the stomach side effects of the class. In REDEFINE 1, 79.6% of people on CagriSema had a gastrointestinal event against 39.9% on placebo, with nausea at 55% and constipation at 30.7%. In TRIUMPH-1, nausea was 42.4% on 12 mg and constipation 26.1%. Vomiting was almost identical, 26.1% against 25.3%.

Retatrutide adds one effect CagriSema's headline report doesn't list: dysesthesia, an odd burning or oversensitive skin, in 12.5% on 12 mg against 0.9% on placebo in TRIUMPH-1. Novo's release does not mention it for CagriSema, so we can't say the rate there.

Stopping rates favor CagriSema. In REDEFINE 1, 5.9% stopped CagriSema for side effects against 3.5% on placebo. In TRIUMPH-1, 11.3% stopped 12 mg against 4.9% on placebo, though only 6.9% stopped 9 mg. With diabetes, 8.4% stopped CagriSema in REDEFINE 2 against 3% on placebo, and in TRIUMPH-2 it was 7.7% on 12 mg and 11.6% on 9 mg against 4.9%. Retatrutide's top dose is higher than CagriSema's single dose, and nobody has tested whether that explains the gap.

Call your doctor for severe stomach pain, repeated vomiting or signs of dehydration on either drug.

Is CagriSema approved, and where does retatrutide stand?

Novo Nordisk submitted a New Drug Application to the FDA for CagriSema on December 18, 2025, for weight management in adults with obesity or overweight and a weight-related condition. Novo's February 2026 announcement said a decision was "anticipated by late 2026." As of October 31, 2026 we found no FDA decision and no public action date. Novo's own release says CagriSema is not approved in the US or EU.

Retatrutide has no filing. Lilly last said, on September 29, 2026, that it plans to submit retatrutide to the FDA in the first quarter of 2027 as a Biologics License Application (BLA). On October 2, 2026, the FDA decided that retatrutide is a drug, not a biological product, so an application would need to be filed under section 505 of the Federal Food, Drug, and Cosmetic Act. Lilly's appeal on that question is pending in the Seventh Circuit, and we found no ruling as of October 31, 2026. Our retatrutide release date page tracks the timeline.

If CagriSema is approved this year, it would reach patients well ahead of retatrutide, which has no filing yet. Lilly's own wording is that retatrutide "is an investigational medicine that is not on the market." Anything sold online as retatrutide is not Lilly's product, and the FDA says retatrutide and cagrilintide cannot be used in compounding under federal law. If you are weighing where people buy retatrutide, read our retatrutide for sale page before spending money on a vial.

Who might prefer which

These are questions to bring to a prescriber, not a verdict.

If you want something you can get on prescription soon, CagriSema is the only one of the two with a pending application. Ask whether waiting on an FDA decision makes sense against starting an approved drug now; our new weight loss drugs hub lists what else is in the queue.

If you need the largest published weight loss, retatrutide's numbers are higher, but they come from trials that gave higher doses for longer, and you can't have it outside a trial yet.

If stomach side effects were hard on you on semaglutide, remember CagriSema contains semaglutide at the same 2.4 mg dose as Wegovy. Our retatrutide vs semaglutide page compares that drug directly. If you've seen people pairing cagrilintide with retatrutide, the cagrilintide stack page covers what is and isn't known.

As of October 2026, both companies still have pending trials: Novo has REDEFINE 11 and a higher-dose CagriSema study planned, and Lilly has TRIUMPH-5 and others.