Cagrilintide

What is Cagrilintide?

Cagrilintide is an experimental, long-acting copy of the peptide hormone amylin. The manufacturer Novo Nordisk is developing it. Researchers are currently studying it for the treatment of obesity and type 2 diabetes. The main focus is on a fixed combination with the GLP-1 drug semaglutide, under the name CagriSema.

The natural hormone amylin is produced in the pancreas alongside insulin. After eating, it signals to the brain 'I am full'. Natural amylin tends to clump together into thread-like structures when in solution. That makes it unsuitable as a drug. Cagrilintide gets around this problem with a fat attachment on the molecule. This attachment is also what gives it its long duration of action of about one week.

How is Cagrilintide used?

In all clinical studies, cagrilintide is given as a once-weekly subcutaneous injection (meaning under the skin) - typically into the abdomen, thigh, or upper arm. The drug comes as a pre-filled pen, not as a lyophilisate (a freeze-dried powder) that would first need to be mixed.

The dose is increased gradually over several weeks (titration). This allows the body to get used to the gastrointestinal side effects, such as nausea. In the REDEFINE studies, the target dose was 2.4 mg of cagrilintide, or 2.4 mg/2.4 mg as the fixed CagriSema combination [1][2].

Gray market reality: Since cagrilintide is not approved either as a monotherapy or as CagriSema, there is no legal access for private users. On the gray market, cagrilintide is currently practically unavailable - unlike approved GLP-1 drugs such as semaglutide, where gray market products are widespread. Should experimental sources appear in the future, using it without medical supervision would carry significant risks. No validated safety data exists outside of clinical studies.

From vial to use: What does this mean in practice?

Since cagrilintide has not yet reached the regular market, there are no official patient-friendly pre-filled pens for private users. In clinical trials, the drug is used as a pre-filled pen that is injected directly - no mixing with BAC water is required.

Calculation example (only to illustrate the study dosage): The target dose of 2.4 mg of cagrilintide per week corresponds to exactly one injection per week with a typical pre-filled pen at a concentration of 2.4 mg per injection. In the CagriSema combination pen, 2.4 mg of cagrilintide and 2.4 mg of semaglutide are contained in a single weekly injection.

If you want to understand the process from powder vial to ready syringe for other peptides, you'll find a tool in the Injection Calculator that works through concentration, volume, and syringe choice. For cagrilintide itself, this process is not relevant as long as only pre-filled pens are used.

Note: This is a descriptive account of study practice, not a guide to self-medication. Cagrilintide is not approved.

How does Cagrilintide work?

Cagrilintide binds in the brainstem to docking sites (receptors) for the body's own satiety hormone amylin, as well as to related calcitonin receptors. This binding strengthens the feeling of fullness and slows down gastric emptying - you feel full sooner and for longer.

A fat attachment on the molecule (a so-called fatty acid side chain) ensures that cagrilintide docks onto the transport protein albumin in the blood. This slows down its breakdown, so it stays active for about a week - hence one injection per week is enough. This technique is similar to that used with semaglutide, which also uses a fat attachment for a long duration of action.

In the CagriSema combination, two different hormone systems are engaged at the same time: semaglutide activates the GLP-1 receptor (stimulating insulin release, suppressing appetite), while cagrilintide activates the amylin receptor (enhancing satiety). The hope is that the effects complement each other, leading to greater weight loss than with either drug alone.

How effective is Cagrilintide?

The clinical efficacy of cagrilintide is supported by comprehensive phase 3 studies. As a monotherapy, a weight loss of about 11.8% over 68 weeks was achieved (REDEFINE 1). In the CagriSema combination, weight loss was -20.4% over 68 weeks in the primary endpoint of REDEFINE 1 (vs. -3.0% under placebo) [1]. Under the efficacy estimand (meaning if all participants had continued treatment as intended), it was even -22.7%.

In REDEFINE 1, 91.9% of CagriSema participants achieved a weight loss of >=5%, compared to 31.5% under placebo. The higher thresholds of >=20% and >=25% were also reached significantly more often (P<0.001 for all comparisons) [1].

For people with type 2 diabetes, REDEFINE 2 showed a weight loss of -15.7% over 68 weeks with CagriSema [2].

The REDEFINE study program

The REDEFINE program comprises the manufacturer's pivotal phase 3 studies. These examined the long-term safety and efficacy of the once-weekly injection over a period of 68 weeks. The key studies:

REDEFINE 4 is particularly noteworthy: here, CagriSema went head-to-head with tirzepatide (Mounjaro/Zepbound), the strongest approved weight-loss drug to date. CagriSema achieved 23.0% weight loss after 84 weeks, but could not prove it was on par with tirzepatide (25.5%) - the primary endpoint of non-inferiority was missed. This raises the question of whether the combination of two drugs justifies the effort when a single drug (tirzepatide) delivers similar or better results.

In addition, the REIMAGINE program for type 2 diabetes is underway, in which CagriSema is being tested for blood sugar reduction (HbA1c). Initial data show an HbA1c reduction of 1.91 percentage points.

Dosage: what the studies show - and the course

In the clinical studies, cagrilintide was given as a once-weekly subcutaneous injection. The dose was increased gradually (titration) to improve tolerability. Tested doses ranged from 1.2 mg to 4.5 mg [3].

The target dose in the REDEFINE studies is 2.4 mg of cagrilintide, or 2.4 mg/2.4 mg as the fixed CagriSema combination [1][2]. In the phase 2 study, 4.5 mg was also tested. This led to greater weight loss, but also to more side effects [3].

These are study doses, not a dosage recommendation. Cagrilintide is not approved.

Side effects and common mistakes

In the phase 3 studies, cagrilintide is generally considered to be well tolerated. By far the most common adverse effects are gastrointestinal complaints. In REDEFINE 1, 79.6% of CagriSema participants experienced gastrointestinal side effects (vs. 39.9% with placebo) - mainly nausea, vomiting, diarrhea, constipation, and abdominal pain [1]. These were mostly temporary and mild to moderate.

Because cagrilintide slows gastric emptying, discomfort can occur especially at the start of treatment or when the dose is increased. Gradual titration is therefore a central part of the study protocol.

There is no standalone safety data for cagrilintide monotherapy outside the REDEFINE program. Long-term safety beyond 68 weeks is not known.

Approval and legal status

Cagrilintide is not approved - neither as a monotherapy nor as the CagriSema combination. In December 2025, Novo Nordisk submitted a New Drug Application (NDA) to the US FDA for CagriSema, based on the REDEFINE 1 and REDEFINE 2 data. A decision is expected in the fourth quarter of 2026.

For Europe (EMA), no public application for approval has been confirmed so far. Cagrilintide as a standalone monotherapy is not under active review for approval.

The REDEFINE 4 results (missed non-inferiority vs. tirzepatide) could influence the approval process, even though the FDA decision is primarily based on REDEFINE 1 and 2. It remains to be seen how the agency will evaluate the head-to-head data.

You can find more information about peptide drugs and their development status in the Peptide Library. If you want to learn more about the safe sourcing of peptides in general, I recommend a look at the Protection section with the Vendor Radar.