CagriSema

Composition and origin

CagriSema is not a single molecule but two peptides given together once a week. Semaglutide is the GLP-1 receptor agonist sold as Ozempic and Wegovy. Cagrilintide is a long-acting analogue of amylin, a 37-amino-acid hormone made by the insulin-producing beta cells of the pancreas. An older amylin analogue, pramlintide, was used in the US alongside insulin in diabetes until AstraZeneca stopped making it in 2025, but Novo Nordisk designed cagrilintide to last far longer: in its phase 1b trial it had a half-life of 159 to 195 hours, close to semaglutide's 145 to 165 hours. That is what makes a shared weekly schedule possible.

In Novo Nordisk's phase 3 trials the two were given together once a week; in REDEFINE 1 the dose was built up over 16 weeks to 2.4 mg of each. The company describes CagriSema as a fixed-dose combination. Cagrilintide on its own is not approved anywhere.

Our product is something else: a research vial with 5 mg of cagrilintide and 5 mg of semaglutide premixed as one powder. The one-to-one ratio by weight matches the combination in the trials, but no study has tested a premixed research powder, and the trial product itself is not available outside clinical trials.

How it works

The two parts act on different receptors. Semaglutide activates the GLP-1 receptor: it raises insulin release when blood glucose is high, lowers glucagon, slows stomach emptying and acts on appetite centres in the brain. Cagrilintide mimics amylin. Amylin receptors are built from a core receptor, the calcitonin receptor, paired with one of several receptor activity-modifying proteins (RAMPs). Amylin acts mainly in the circumventricular organs, small brain areas with a leaky blood-brain barrier such as the area postrema in the brainstem, and it helps regulate blood glucose and energy metabolism.

Because the pathways are separate, their effects on appetite can add up. For weight the trials bear that out: in REDEFINE 1 the combination beat both components given alone. For blood sugar the extra gain is small: in REIMAGINE 2, assuming everyone kept taking the treatment, HbA1c fell 1.91 percentage points on the combination against 1.75 on semaglutide 2.4 mg alone, a difference of 0.16 points that was statistically significant.

Is CagriSema approved?

No. CagriSema is not authorised in any country yet.

In the United States, Novo Nordisk submitted it to the FDA in December 2025 for weight management, on the basis of REDEFINE 1 and 2. In its half-year report of August 2026, and again in September 2026, the company said it expected the FDA's decision in the fourth quarter of 2026. By 28 October 2026 no decision had been announced.

In the EU there is no marketing authorisation, and the EMA's list of new medicines under evaluation, with data of 5 October 2026, contains no application for cagrilintide, alone or in combination. In the Netherlands it is therefore not available as a medicine. Dutch participants have taken part in the research: REDEFINE 1 had sites in Amsterdam, Arnhem, Hoofddorp, Roosendaal and Zwijndrecht.

Research-grade cagrilintide and semaglutide, whether sold separately or premixed, are not this medicine. They have no marketing authorisation and may not be used in people.

In sport, semaglutide is permitted. WADA class S0 prohibits at all times any substance that no other section of the list covers and that has no current approval from any health authority for human therapeutic use, including drugs still in clinical development. Cagrilintide is not named on the list, but it has no such approval, so it falls under S0. The Dutch Dopingautoriteit applies the same WADA list.

What the research shows

CagriSema has been through phase 1 and 2 trials and two phase 3 programmes, REDEFINE in obesity and REIMAGINE in type 2 diabetes, all run and funded by Novo Nordisk. The phase 1b, REDEFINE 1 and 2 and REIMAGINE 2, among others, have been published in journals; REDEFINE 4, REDEFINE 9 and REIMAGINE 4 and 5 are so far known only from company announcements and have not been peer-reviewed. Results are reported in two ways: one counts everyone, whether or not they kept taking the drug, the other assumes everyone did and gives larger numbers. The first is used below unless stated otherwise.

• Phase 1b (Lancet 2021): 96 adults with overweight or obesity were randomised to semaglutide 2.4 mg plus cagrilintide or placebo for 20 weeks (95 received treatment). Weight fell 17.1% with cagrilintide 2.4 mg added, against 9.8% with semaglutide plus placebo.
• REDEFINE 1 (NEJM 2025): 3,417 adults with obesity or overweight and no diabetes, 68 weeks. Weight −20.4% on the combination, −14.9% on semaglutide alone, −11.5% on cagrilintide alone and −3.0% on placebo. The protocol let participants adjust their dose, and at week 68 only 57.3% of the combination group were on the full dose. Had everyone kept taking it, the loss would have been 22.7%, with 40.4% losing at least a quarter of their weight.
• REDEFINE 2 (NEJM 2025): 1,206 adults with type 2 diabetes and obesity or overweight, 68 weeks. Weight −13.7% against −3.4% on placebo; 73.5% reached an HbA1c of 6.5% or lower against 15.9%.
• REIMAGINE 2 (Lancet Diabetes & Endocrinology 2026): 2,713 adults with type 2 diabetes on metformin, with or without an SGLT2 inhibitor, 68 weeks. Assuming everyone kept taking it, HbA1c fell 1.91 percentage points on the combination against 1.75 on semaglutide 2.4 mg.
• REDEFINE 4 (announced February 2026): 809 adults with obesity, open-label, 84 weeks against tirzepatide 15 mg. Weight −20.2% against −23.6%; the trial missed its main goal of showing that CagriSema was no worse than tirzepatide.
• REIMAGINE 4 (reported August 2026): open-label, 68 weeks against tirzepatide 15 mg in type 2 diabetes. Assuming everyone kept taking it, weight −15.2% against −15.8%, which passed the test for being no worse, and HbA1c −1.9 against −2.2 percentage points, which did not.
• REIMAGINE 5 and REDEFINE 9 (announced September 2026), both at the lower dose of 1.0 mg + 1.0 mg and assuming everyone kept taking it: in type 2 diabetes, weight −12.4% against −9.1% on tirzepatide 5 mg after 60 weeks, with a similar HbA1c drop (1.71 against 1.67 percentage points); in overweight and obesity, weight −21.0% against −2.0% on placebo after 68 weeks.
• Still running: REDEFINE 3, a cardiovascular outcome trial in 7,101 people with established heart or vascular disease; REDEFINE 11, expected to report in the first half of 2027; and a phase 3 trial of a higher dose, expected in the first half of 2028.

Side effects and warnings

The side effects are mainly gastrointestinal: nausea, vomiting, diarrhoea, constipation and abdominal pain. In REDEFINE 1, 79.6% of the combination group reported a gastrointestinal adverse event against 39.9% on placebo; in REDEFINE 2, 72.5% against 34.4%. Most were mild to moderate and passed with time. In REDEFINE 1 fewer than six in ten participants on the combination were on the full dose at the end; the company's announcement did not say why.

Because CagriSema has no approved product information yet, there is no official list of warnings for the combination. The warnings in semaglutide's own product information, such as pancreatitis, gallbladder disease and thyroid C-cell tumours in rodents, apply to its semaglutide half. The longest trial reported so far ran 84 weeks; the cardiovascular outcome trial REDEFINE 3 is meant to add longer-term safety data.

CagriSema versus semaglutide and tirzepatide

Against semaglutide alone the data favour the combination: 20.4% against 14.9% weight loss in REDEFINE 1, and a slightly larger HbA1c drop in REIMAGINE 2. Against tirzepatide, the GIP and GLP-1 agonist sold as Mounjaro, the picture depends on the dose. At the top doses, tirzepatide 15 mg produced more weight loss in REDEFINE 4, and in type 2 diabetes REIMAGINE 4 found similar weight loss but a smaller HbA1c drop with CagriSema. At lower doses, REIMAGINE 5 found more weight loss with CagriSema 1.0 mg + 1.0 mg than with tirzepatide 5 mg. Comparisons between separate trials, such as setting REDEFINE 1 next to tirzepatide's own trials, are unreliable because the people and designs differ.

Novo Nordisk is now testing a higher dose, cagrilintide 2.4 mg with semaglutide 7.2 mg, against both the standard combination and semaglutide 7.2 mg alone.

Frequently asked questions

Is CagriSema approved?

Not yet. Novo Nordisk filed it with the FDA in December 2025 for weight management and expects a decision in the last quarter of 2026; none had been announced by 28 October 2026. In the EU no application was under evaluation in October 2026.

Is CagriSema legal in the Netherlands?

There is no CagriSema medicine on the Dutch market, so it is not available on prescription; people in the Netherlands have received it only within clinical trials such as REDEFINE 1. Research-grade cagrilintide and semaglutide are sold as laboratory material, not as a medicine, and may not be used in people.

How much weight did people lose on CagriSema?

In REDEFINE 1, adults without diabetes lost 20.4% of their body weight over 68 weeks, or 22.7% had everyone kept taking it; placebo gave 3.0%. People with type 2 diabetes lost less: 13.7% in REDEFINE 2. In the open-label REDEFINE 4 trial the average was 20.2% after 84 weeks.

Is CagriSema better than Mounjaro?

Not at the top doses, on the evidence so far. In REDEFINE 4, the only head-to-head obesity trial, tirzepatide 15 mg (Mounjaro) gave 23.6% weight loss against 20.2% for CagriSema after 84 weeks, and CagriSema missed its goal of showing it was no worse. In type 2 diabetes, REIMAGINE 4 found similar weight loss but a larger HbA1c drop with tirzepatide 15 mg, while REIMAGINE 5 found more weight loss with low-dose CagriSema (1.0 mg + 1.0 mg) than with tirzepatide 5 mg. All three results come from company announcements, not yet from journal papers.

Is CagriSema banned in sport?

The cagrilintide in it is. Semaglutide is not on the WADA Prohibited List, but cagrilintide has no approval from any health authority, which puts it in class S0, non-approved substances, prohibited in and out of competition. That applies to research-grade cagrilintide too, and the Dutch Dopingautoriteit applies the same list. Once any health authority approves it, cagrilintide would no longer meet the S0 definition.

Is a research blend of cagrilintide and semaglutide the same as CagriSema?

No. CagriSema is Novo Nordisk's product, made and tested under pharmaceutical rules and given in its trials once a week at fixed doses. A research vial holds the same two peptides, in our case 5 mg of each premixed as a powder, but its identity and purity are what a certificate of analysis says, nothing more, and this premixed form has never been studied in people. It may not be used in people.

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.

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