CagriSema: what it is, what the REDEFINE trials found and why it disappointed

On paper, CagriSema was the drug that was going to dethrone Mounjaro. The story of what happened next is more interesting than the headline — and it explains better than any other example why you should never trust comparisons of figures across different trials.

CagriSema is not authorised in Spain

It is not approved in any country in the world. Novo Nordisk filed its application with the FDA on 18 December 2025 and it is still under review. In the European Union the company has not even announced that it has filed an application. We have checked this directly against the AEMPS register: zero results.

This is not a technicality: it means no Spanish prescription can be written for it and no Spanish pharmacy can dispense it. If a website offers it to you, it is not selling a medicine with any guarantees behind it — whatever turns up at your door, nobody has verified what is in it.

What it is

It is a combination of two molecules in a single weekly injection: semaglutide 2.4 mg — the same one in Wegovy — and cagrilintide 2.4 mg, which is the genuinely new part.

You will already know about semaglutide if you have read what GLP-1s are and how they work. Cagrilintide is something else: an amylin analogue, a hormone distinct from GLP-1 that also plays a part in the satiety signal, acting on different areas of the brain. The bet was that two different hormones would add up to more than one.

What REDEFINE-1 found

3,417 participants with obesity, or overweight with a related complication, without diabetes, over 68 weeks. Published in the New England Journal of Medicine in June 2025. And with a more honest design than usual: it compared not only against placebo, but also against each of its two molecules separately, which is the only way to know whether the combination adds anything.

Weight loss at 68 weeks, among those who stayed on treatment:

• CagriSema — −22.7%
• Placebo — −2.3%

Counted the other way — including everyone who started, whether they dropped out or not — the figure is −20.4% versus −3.0%. Four in ten participants lost at least 25% of their body weight.

Why −22.7% counts as a disappointment

Because Novo Nordisk had spent a long time telling the market to expect 25%. On the day it published these results, in December 2024, its shares fell by around 20%. That figure is financial context, not clinical: it says nothing about whether the drug works. We include it because it explains why you will find this drug described as a "failure" in outlets that cover the stock market rather than medicine. Weight loss of −22.7% is not a clinical failure at all.

There is one nuance Novo made much of, and it is a real one: at 68 weeks only 57.3% of participants were on the maximum dose, because the protocol allowed investigators to keep people on lower doses. That can be read as the drug having more to give. It can equally be read as many people not tolerating the high dose. The data do not distinguish between the two readings.

REDEFINE-2: with type 2 diabetes

1,206 participants with obesity and type 2 diabetes, 68 weeks, also published in the NEJM. Weight loss was −15.7%, versus −3.1% with placebo, among those who stayed on treatment; counting everyone, the NEJM figure is −13.7% versus −3.4%. That this is considerably less than in REDEFINE-1 is exactly what you would expect: in people with type 2 diabetes these drugs usually deliver considerably less weight loss.

REDEFINE-4: the figure that really matters

This is the trial almost nobody talks about, and it is the only one that proves anything. 809 participants, 84 weeks, and this time not against placebo: against tirzepatide 15 mg, the highest dose of Mounjaro. Head to head, the same people, at the same time.

• CagriSema — −23.0%
• Tirzepatide 15 mg — −25.5%

CagriSema did not just fail to win: it missed its non-inferiority endpoint. In other words, it could not even demonstrate that it was equivalent. Novo reported these results in February 2026 and, as of today, they have not been published in any peer-reviewed journal.

Here is the lesson of this whole article

If you compare the figures in isolation, CagriSema (−22.7%) looks as though it beats tirzepatide (−20.9%). When they were actually measured against each other, in the same trial, tirzepatide won by two and a half points. Neither figure is false. What was false was the comparison.

The side effects

In REDEFINE-1, versus placebo:

• Any gastrointestinal side effect — 79.6% versus 39.9%
• Nausea — 55.0% versus 12.6%
• Constipation — 30.7% versus 11.6%
• Vomiting — 26.1% versus 4.1%
• Discontinuation due to adverse effects — 6.0% versus 3.7%

Four in five participants had some digestive upset. Most cases were mild or moderate and temporary. How these symptoms are managed with the drugs that are actually available is something we cover in side effects of Ozempic and Mounjaro and how they are managed.

How it compares with what already exists (and why the comparison is misleading)

This is the table everyone publishes. We are publishing it too, with the warning almost nobody adds: these figures are NOT comparable with one another.

• Semaglutide 2.4 mg (Wegovy) — STEP-1: −14.9% at 68 weeks, versus −2.4% with placebo. Published in NEJM (2021).
• Tirzepatide 15 mg (Mounjaro/Zepbound) — SURMOUNT-1: −20.9% at 72 weeks, versus −3.1% with placebo. Published in NEJM (2022).
• Orforglipron 36 mg (Foundayo) — ATTAIN-1: −12.4% at 72 weeks. Published in NEJM (2025).
• Retatrutide 12 mg — TRIUMPH-1: −28.3% at 80 weeks. Lilly press release and presentation at ADA 2026. Not published in a peer-reviewed journal.
• CagriSema 2.4/2.4 mg — REDEFINE-1: −22.7% at 68 weeks, versus −2.3% with placebo. Published in NEJM (2025).

Why you cannot read that list as a ranking

• The trials run for different lengths of time. From 68 to 84 weeks. Weight loss curves have not reached a plateau by 68 weeks, so giving a drug 12 extra weeks hands it an advantage without it having done anything better.
• The populations are different. Starting weight, age, sex and comorbidity do not match. The same molecule is known to produce considerably less weight loss in people with type 2 diabetes than in people without it: mixing populations invalidates any ordering.
• The placebos do not match. The placebo group lost −2.4% in STEP-1, −3.1% in SURMOUNT-1 and −2.2% in TRIUMPH-1. A different placebo means a different lifestyle intervention behind it — that is, a different starting line.
• Not all the figures are peer-reviewed. Four come from the New England Journal of Medicine. The retatrutide figure comes from a company press release. They are not the same class of evidence.

The only thing that does prove something: the two head-to-head trials

Only twice have two of these drugs gone up against each other in the same trial, with the same people and at the same time. These are the only data on this page that allow anyone to say one is better than another.

• SURMOUNT-5 — tirzepatide 15 mg versus semaglutide 2.4 mg, 72 weeks: −20.2% versus −13.7%. Tirzepatide won.
• REDEFINE-4 — CagriSema versus tirzepatide 15 mg, 84 weeks: −23.0% versus −25.5%. It missed its non-inferiority endpoint. In other words: CagriSema could not even demonstrate that it was equivalent.

Note the contrast. In the list above, CagriSema (−22.7%) looks as though it beats tirzepatide (−20.9%). When they were actually measured head to head, tirzepatide won. That is exactly what it means to say that figures from different trials are not comparable — and why that list is not a ranking.

Orforglipron and retatrutide have never been measured against anything other than placebo. When someone tells you that one of the two "is better" than what already exists, there is no trial at all behind that sentence.

What is available in Spain today

CagriSema is not authorised in Spain as things stand, and its head-to-head against tirzepatide (REDEFINE-4) is a reminder that tables built from separate trials are not a ranking. That is the point to hold on to.

In the meantime, losing weight under medical supervision does not have to wait for any launch. Medical weight-loss treatment is available in Spain today, with a prior assessment, a prescription where appropriate from a registered doctor, and ongoing follow-up from the medical team. You can check whether you are eligible.

And to keep getting to grips with the subject: what GLP-1s are and how they work, how Mounjaro and Ozempic differ and the only legal route to accessing them.