Cagrilintide

Origin and structure

Amylin is a 37-amino-acid hormone that the insulin-producing beta cells of the pancreas release together with insulin after a meal. It is an awkward starting point for a drug, because natural amylin readily clumps into amyloid fibrils. Pramlintide (Symlin), an amylin analogue approved in the US since 2005, swaps three of amylin's amino acids for proline, but it is short-acting and had to be injected before each main meal; it has not been made since 2025.

Novo Nordisk chemists described cagrilintide in 2021 as the result of a structure-activity programme aimed at a stable, long-acting version (Kruse et al., J Med Chem). It keeps amylin's length of 37 amino acids, differs from human amylin at six positions, including pramlintide's three prolines, and carries a 20-carbon fatty acid attached through a glutamic-acid linker to the start of the chain. That lipid chain is what makes it long-acting: in a phase 1b trial its half-life was 159 to 195 hours, about a week. In development it was known as AM833 and NNC0174-0833.

How it works

Cagrilintide imitates amylin. Amylin slows the emptying of the stomach, holds back the release of glucagon after a meal and reduces food intake through the brain's control of appetite. Cagrilintide is built to keep that signal running for the whole week between injections.

Amylin's receptors are made of the calcitonin receptor paired with one of three helper proteins (RAMP1, 2 or 3). Cagrilintide activates both these amylin receptors and the calcitonin receptor itself, which is why it is described as a dual amylin and calcitonin receptor agonist. In a study in obese mice, cagrilintide lost much of its potency in animals lacking the helper proteins RAMP1 and RAMP3, which the authors read as dependence on amylin receptors 1 and 3; it also switched on neurons in two brainstem areas involved in appetite, the dorsal vagal complex and the lateral parabrachial nucleus.

Amylin and GLP-1 act through different receptors, and most of cagrilintide's late-stage development has been in combination with semaglutide, as CagriSema. Separately, a Novo Nordisk trial in Denmark (RAMBO) is testing whether cagrilintide slows the loss of bone density that comes with weight loss in postmenopausal women.

Is cagrilintide approved?

No. No medicine containing cagrilintide has been approved in the EU, the US or elsewhere. In the Netherlands it is not a registered medicine, so it may not be sold or promoted for use in people; research-grade cagrilintide is laboratory material, which is the basis on which our shop sells it.

Its route to market runs mainly through CagriSema, Novo Nordisk's fixed-dose combination of cagrilintide and semaglutide, given together once a week. Novo Nordisk filed it with the FDA for weight management in December 2025, based on the REDEFINE 1 and REDEFINE 2 trials, and said in February 2026 that it expected a decision by late 2026. An approval of CagriSema would cover that combination product only.

Cagrilintide on its own has a separate phase 3 programme, RENEW, which began in November 2025 with two placebo-controlled 64-week trials: one in adults with overweight or obesity and one in adults who also have type 2 diabetes.

In the US, the FDA states that cagrilintide may not be used by compounding pharmacies, because it is not a component of any FDA-approved drug and has not been found safe and effective for any condition.

In sport, WADA class S0 prohibits at all times any substance that no other section of the list covers and that has no current approval for human therapeutic use anywhere, explicitly including drugs still in clinical development. Cagrilintide is not named on the list, but it falls under this class for as long as no product containing it is approved anywhere. In the Netherlands the Dopingautoriteit applies the same list, where the class is called 'niet erkende stoffen'.

What the research shows

Almost all human data come from trials run and funded by Novo Nordisk. For cagrilintide on its own there is one completed dose-finding trial and the single-drug arms of larger combination trials; the first phase 3 trials of cagrilintide alone started in November 2025 and have not reported.

• Phase 2 dose-finding trial (Lau et al., Lancet 2021): 706 adults with overweight or obesity and no diabetes at 57 sites in ten countries, randomised to one of five weekly doses of cagrilintide, daily liraglutide or placebo for 26 weeks. Body weight fell 6.0% to 10.8% with cagrilintide, depending on dose, against 3.0% with placebo; the highest dose also beat liraglutide (10.8% versus 9.0%).
• Phase 1b with semaglutide (Enebo et al., Lancet 2021): 96 otherwise healthy adults with overweight or obesity. After 20 weeks, the three highest cagrilintide doses added to semaglutide gave 15.4% to 17.1% weight loss, against 8.0% to 9.8% on semaglutide with placebo. The trial was designed to test safety, not weight loss.
• Phase 2 in type 2 diabetes (Frias et al., Lancet 2023): 92 adults on metformin, with or without an SGLT2 inhibitor, for 32 weeks. Body weight fell 8.1% on cagrilintide alone, 5.1% on semaglutide alone and 15.6% on the combination; HbA1c fell 0.9, 1.8 and 2.2 percentage points.
• REDEFINE 1 (Garvey et al., NEJM 2025): 3,417 adults with overweight or obesity and no diabetes, at 256 sites in 23 countries including five Dutch hospitals, followed for 68 weeks; 302 received cagrilintide alone. Estimated as if everyone had kept taking the treatment, weight fell 11.8% on cagrilintide alone, 16.1% on semaglutide alone, 22.7% on the combination and 2.3% on placebo. Counting everyone regardless of adherence, the combination reached 20.4% against 3.0%.
• REDEFINE 4 (headline results, February 2026): in this open-label trial against tirzepatide 15 mg in 809 adults with obesity and at least one related condition, the combination gave 20.2% weight loss over 84 weeks against 23.6% for tirzepatide, counting everyone regardless of adherence (23.0% against 25.5% if everyone had kept taking the treatment). It missed its primary endpoint: showing that the combination was not inferior to tirzepatide.
• Under way: RENEW 1 (300 adults with overweight or obesity) and RENEW 2 (330 with type 2 diabetes), placebo-controlled trials of cagrilintide alone due to complete their main phase in 2027; a phase 3 trial of cagrilintide, semaglutide and the combination in about 460 children and adolescents aged 8 to 18, with sites in 's-Hertogenbosch and Amersfoort; REDEFINE 3, a cardiovascular outcomes trial of the combination in 7,101 people with heart or vascular disease, with nine Dutch sites; and RAMBO, on bone density during weight loss.

Side effects and warnings

In every trial the main side effects were gastrointestinal. In the phase 2 trial, 41% to 63% of participants on cagrilintide had a gastrointestinal adverse event, depending on dose, against 32% on placebo, mostly nausea (20% to 47% against 18%); constipation, diarrhoea and injection-site reactions were also among the most frequent. Over the 26 weeks, 10% of all participants stopped treatment for good, at similar rates across the groups, most often because of side effects.

A thorough QT study in 105 healthy volunteers found no clinically relevant effect on the heart's electrical recovery at the highest dose used in the trials. In the phase 2 trial in type 2 diabetes, no clinically significant or severe low blood sugar was reported.

What is not known: there are no data beyond 68 weeks for cagrilintide alone and no cardiovascular-outcome data for it; REDEFINE 3 tests the combination, not cagrilintide on its own. The older amylin analogue pramlintide carries a US boxed warning for severe low blood sugar when used with insulin, and the published trials of cagrilintide alone did not include people using insulin.

Cagrilintide versus pramlintide and semaglutide

Pramlintide (Symlin) was approved in the US in 2005 for people with type 1 or type 2 diabetes who use mealtime insulin and have not reached their glucose targets, and was injected before each main meal; AstraZeneca stopped making and supplying it in 2025, and it was never authorised in the EU. Cagrilintide is a different molecule with a different aim: one injection a week, developed for weight management rather than as an add-on to insulin.

Semaglutide works through the GLP-1 receptor, a separate hormone pathway. In REDEFINE 1 it produced more weight loss on its own than cagrilintide did (16.1% against 11.8% at 68 weeks), and the two together produced the most (22.7%). In the small phase 2 trial in type 2 diabetes the order of the single drugs was reversed for weight (8.1% against 5.1% at 32 weeks), but semaglutide lowered HbA1c twice as much (1.8 against 0.9 percentage points). With about 30 people per group, that trial was too small to settle the comparison.

Frequently asked questions

Is cagrilintide legal in the Netherlands?

It is not a registered medicine in the Netherlands or anywhere else, so it may not be sold, advertised or supplied for use in people; it is available only as research material. For athletes under anti-doping rules it is prohibited at all times as a non-approved substance (WADA class S0), regardless of how it was obtained.

What is the difference between cagrilintide and CagriSema?

Cagrilintide is the single molecule, an amylin analogue. CagriSema is Novo Nordisk's fixed-dose combination of cagrilintide and semaglutide, given together once a week. Most of the phase 3 evidence is for CagriSema, which was filed with the FDA in December 2025; cagrilintide alone has its own phase 3 programme, RENEW, which started in November 2025.

How much weight do people lose on cagrilintide alone?

In the phase 2 trial, 6.0% to 10.8% over 26 weeks depending on dose, against 3.0% on placebo. In REDEFINE 1, 11.8% over 68 weeks, estimated as if everyone had kept taking the treatment, against 2.3% on placebo. Both trials were in adults with overweight or obesity and no diabetes. In type 2 diabetes a small phase 2 trial found 8.1% over 32 weeks. The phase 3 trials of cagrilintide alone are due to complete their main phase in 2027.

Is cagrilintide banned in sport?

Yes, at all times. It is not named on the WADA Prohibited List, but class S0 prohibits any substance that no other section covers and that has no current approval for human therapeutic use, including drugs in clinical development, and no product containing cagrilintide is approved. That status rests on the missing approval: S0 covers only substances that are approved nowhere. The Dutch Dopingautoriteit applies the same list.

What are the side effects of cagrilintide?

Mainly stomach and bowel complaints. In the phase 2 trial nausea affected 20% to 47% of participants on cagrilintide, depending on dose, against 18% on placebo, and constipation, diarrhoea and injection-site reactions were also common. A dedicated QT study found no clinically relevant effect on the heart's electrical recovery. Data beyond 68 weeks, and cardiovascular-outcome data for cagrilintide alone, do not exist yet.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.