Cagrilintide / CagriSema

Amylin, the second satiety system

Amylin is a hormone most people have never heard of, even though it is released together with insulin — from the same cells, at the same moment. Insulin regulates sugar. Amylin tells the brain that it has had enough. Cagrilintide is a long-acting replica of this hormone.

This is the crucial point: the well-known weight-loss injections all work on the GLP-1 system. Amylin is a different route to the same goal. Anyone who targets both systems at once presses two different buttons instead of pressing one harder. That is exactly what CagriSema does, the combination of cagrilintide and semaglutide in one injection.

REDEFINE 1 and the two numbers

REDEFINE 1 enrolled 3,417 adults with overweight or obesity, ran for 68 weeks and was placebo-controlled. The result: 22.7 percent weight loss versus 2.3 percent on placebo. For a person weighing 100 kilograms, that is more than 20 kilos. This is in the range otherwise known only from stomach surgery.

But the trial reports two numbers, and they measure different things. 22.7 percent is the value for those who took the drug as intended. 20.4 percent is the value for all participants — including those who stopped, switched or did not stick with it. The second number is the more honest one, because it includes what actually happens in life. Promotional material almost always quotes the first. The difference here was more than 2 percentage points.

Why a success was reported as a disappointment

The headlines read missed, disappointing, share price loss; the stock fell by around 20 percent in a single day. The reason was not the result but a promise: the company had previously spoken of 25 percent. The gap between announcement and result was the news.

For an investor, the question is whether a drug beats the competition clearly enough to turn the market. In the direct comparison with tirzepatide over 84 weeks (REDEFINE 4), CagriSema then reached 23.0 versus 25.5 percent in 2026 and missed the goal of being equivalent. From a patient's point of view, the question is a different one, namely whether it helps, and there the answer is yes. The two questions have nothing to do with each other and are answered in the same headline. When it says somewhere that a drug disappointed, the next question is: disappointed whom?

Cagrilintide alone is something else

The trial everyone is talking about tested the combination. Cagrilintide alone was tested in a phase 2 trial lasting 26 weeks: at the highest dose, weight fell by 10.8 percent, on placebo by 3.0 percent. REDEFINE 1 also had a trial arm with cagrilintide only. The values are markedly below those of the combination, and the point of the exercise is to use two routes at the same time.

This leads to the practical point: anyone who buys cagrilintide as a single substance on the gray market is buying neither the combination from the large trials nor the tested trial drug.

What the studies show

REDEFINE 1 — 3,417 adults, 68 weeks, placebo-controlled

REDEFINE 1 tested CagriSema, the combination of cagrilintide and semaglutide, in 3,417 adults with overweight or obesity over 68 weeks against placebo. Weight loss was 22.7 percent in participants who took the drug as intended and 20.4 percent across all participants, versus 3.0 percent on placebo. Almost 80 percent of participants reported gastrointestinal complaints such as nausea, constipation and vomiting, versus 40 percent on placebo. 6 percent stopped because of them, versus just under 4 percent on placebo. The data are published in the New England Journal of Medicine.

REDEFINE 4 — direct comparison with tirzepatide, 84 weeks

In the direct comparison with tirzepatide, CagriSema reached 23.0 versus 25.5 percent weight loss and thus missed the goal of being equivalent. Novo Nordisk announced the results in February 2026.

What is missing on cagrilintide alone

The big numbers apply to the combination, not to cagrilintide as a single substance. There are markedly fewer data on the single peptide: one phase 2 trial over 26 weeks with 10.8 percent weight loss at the highest dose and one comparison arm in REDEFINE 1. Anyone who buys a single peptide with 22.7 percent in mind is transferring the number for the combination to a substance that was markedly weaker on its own.

Everything beyond 68 weeks also remains open: how weight behaves after stopping, what tolerability looks like over years, what two simultaneously targeted satiety systems do in the long term. And the number used in advertising is regularly the more favorable of the two. The question with any weight-loss injection is therefore whether the number given applies to all participants or only to those who stuck with it.

Status, approval and legal

Cagrilintide is not yet approved, and this sets the substance apart from most peptides in this field only in its timeline: it is coming through the regular route. The application for approval of CagriSema has been with the FDA since December 18, 2025; a decision is pending (as of October 2026). It is not approved in the EU either. The phase 3 data are published, in the New England Journal of Medicine. Anyone who can wait will eventually get the drug with a package leaflet, in tested quality and with medical supervision. That is rarely the case with comparable substances and a strong argument for waiting. What is currently offered under the name on the gray market is neither tested nor identical to what was administered in the trial.

Safety

The price is in the trial. Almost 80 percent of participants had gastrointestinal complaints — nausea, constipation, vomiting. On placebo, it was 40 percent. Two things belong with this: first, this is known for this drug class and mostly temporary, especially in the phase in which the dose is slowly increased. Second, only 6 percent stopped because of it, versus just under 4 percent on placebo. Still, you should know the number: anyone who imagines such an injection as an easy route should know that four out of five people have complaints with it. That is not an argument against it but the information needed for a decision. These drugs belong in medical hands anyway, because losing more than 20 kilos in a year is an intervention in metabolism that someone should supervise.

Sources

• Garvey et al., N Engl J Med 2025 (REDEFINE 1)
• Lau et al., Lancet 2021 (cagrilintide as a long-acting amylin analog)
• Lutz, Neuropharmacology 2025 (amylin as a satiety hormone)
• Enebo et al., Lancet 2021 (CagriSema, combination of the amylin and GLP-1 approaches)
• Novo Nordisk, announcement of 2026-02-23 (REDEFINE 4, CagriSema versus tirzepatide)