Cagrilintide: what it is, how it works and the CagriSema trials

Amylin is a hormone released from the pancreas together with insulin after meals, and it promotes a feeling of fullness. Natural amylin clumps into amyloid fibrils easily, which makes it hard to use as a drug; the older analogue pramlintide needs injections three times a day. Novo Nordisk’s 2021 development paper describes cagrilintide as a stable, lipidated analogue designed to last long enough for once-weekly dosing ^[1].

Most of the clinical programme tests cagrilintide in a fixed combination with the GLP-1 agonist semaglutide, called CagriSema. Cagrilintide on its own is sold online as a research peptide; that material has no connection to Novo Nordisk’s clinical product. See what research peptides are.

Amylin is a 37-amino-acid peptide hormone made by the beta cells of the pancreas, the same cells that make insulin. A 2015 review in Pharmacological Reviews describes its main role as a glucose-regulating hormone and an important regulator of energy balance. It acts mainly on the circumventricular organs of the brain, areas where the blood–brain barrier is weaker, and it interacts with other appetite-related hormones such as cholecystokinin and leptin. The review also notes reported effects on the cardiovascular system and bone, and that clinical studies suggested amylin agonists could help weight loss, especially in combination with other agents ^[8].

Amylin does not have a single receptor of its own. Its receptors are formed when the calcitonin receptor pairs with one of three receptor activity-modifying proteins (RAMP1, RAMP2 or RAMP3), giving the amylin receptor subtypes AMY1, AMY2 and AMY3 ^[8]. The older amylin drug pramlintide is used in the US for type 1 and type 2 diabetes alongside insulin ^[8], but it needs three injections a day because of its short half-life ^[1].

Cagrilintide acts on amylin receptors, which are involved in satiety and slowing stomach emptying. Because amylin and GLP-1 act through different receptors, the rationale for CagriSema is that the two signals add together. In the phase 1b study, cagrilintide had a half-life of about 159 to 195 hours, supporting weekly injection, and it did not alter the exposure or elimination of semaglutide given at the same time ^[2].

The cagrilintide mechanism of action has been studied at the receptor level. A 2025 structural study solved the shapes of cagrilintide bound to all three amylin receptors and to the calcitonin receptor. It found that cagrilintide binds in an amylin-like way but produces different receptor movements from other peptides in this family, which the authors suggest could contribute to its effects ^[10]. For this reason cagrilintide is described as an amylin and calcitonin receptor agonist, not a pure amylin mimic.

Work in mice points to where the weight effect comes from. In mice lacking RAMP1 and RAMP3, and therefore lacking AMY1 and AMY3 receptors, cagrilintide lost much of its effect on body weight, and it activated neurons in brainstem areas that control appetite in normal mice ^[9]. In the same study, salmon calcitonin, which also acts on these receptors, did not reduce body weight in normal mice, which shows that drugs in this family do not all behave alike ^[9]. These are animal findings and describe mechanism, not effects in people.

No. The cagrilintide peptide is an amylin analogue and does not act on the GLP-1 receptor. It is often grouped with GLP-1 drugs because its main clinical use is in CagriSema, which pairs it with the GLP-1 receptor agonist semaglutide. The phase 3 trial reports describe cagrilintide as an amylin receptor agonist and semaglutide as a GLP-1 receptor agonist, with complementary effects ^[16].

Cagrilintide alone was tested in a 26-week phase 2 dose-finding trial in 706 adults with obesity or overweight but without diabetes. Weekly doses from 0.3 mg to 4.5 mg reduced body weight by 6.0% to 10.8%, against 3.0% on placebo, when participants stayed on treatment. The top dose, 4.5 mg, produced more weight loss than daily liraglutide 3.0 mg (10.8% against 9.0%) ^[3].

That phase 2 trial ran at 57 sites in ten countries, including the UK, with roughly 100 people in each cagrilintide dose group. About 10% of participants stopped treatment permanently, at similar rates across groups, most often because of adverse events (4% overall). The trial also included a 6-week follow-up period without treatment ^[3].

The earlier phase 1b study gave cagrilintide from 0.16 mg to 4.5 mg with semaglutide 2.4 mg to 96 otherwise healthy adults with overweight or obesity, without lifestyle advice. At 20 weeks, the 4.5 mg group had lost 15.4% of body weight against 8.0% for semaglutide with placebo. The share of people reporting at least one adverse event was similar across groups ^[2].

In type 2 diabetes, a 32-week phase 2 trial in 92 people compared CagriSema with each component alone. HbA1c fell by 2.2 percentage points with CagriSema, 1.8 with semaglutide and 0.9 with cagrilintide, and body weight fell by 15.6%, 5.1% and 8.1% respectively ^[4].

The phase 3 REDEFINE 1 trial enrolled 3,417 adults with obesity or overweight without diabetes for 68 weeks. CagriSema (2.4 mg of each drug weekly) reduced body weight by 20.4% against 3.0% on placebo, using the treatment-policy estimand ^[5]. REDEFINE 2, in 1,206 adults with type 2 diabetes and overweight or obesity, found 13.7% weight loss with CagriSema against 3.4% on placebo, and 73.5% of those on CagriSema reached an HbA1c of 6.5% or less ^[6]. REDEFINE 2 randomised 904 people to CagriSema and 302 to placebo across 12 countries, and gastrointestinal adverse events affected 72.5% on CagriSema against 34.4% on placebo ^[6].

CagriSema is not a single molecule. It is cagrilintide and semaglutide given together once weekly, each at 2.4 mg in the main phase 3 trials ^[5]. REDEFINE 1 enrolled adults without diabetes who had a BMI of 30 or more, or 27 or more with at least one obesity-related condition. Its two main measures were the change in body weight and the share of people losing at least 5%, and it also tested reductions of 20%, 25% and 30% or more, all of which were reached more often on CagriSema than on placebo ^[5]. REDEFINE 1 randomised its 3,417 participants in a 21:3:3:7 ratio: 2,108 to CagriSema, 302 to semaglutide alone, 302 to cagrilintide alone and 705 to placebo, all with lifestyle advice, for 68 weeks ^[5]. The published abstract reports the CagriSema-versus-placebo comparison; it does not report the result of the cagrilintide-alone arm.

CagriSema weight loss was the main result: −20.4% against −3.0% on placebo, using the treatment-policy estimand, which counts everyone randomised whether or not they kept taking the drug ^[5]. A secondary analysis of the same trial found systolic blood pressure fell by 10.9 mmHg on CagriSema against 2.8 mmHg on placebo, and 39.6% of people taking blood-pressure medicine reduced or stopped it, against 18.8% on placebo. Diastolic pressure fell by 5.4 against 1.7 mmHg, and 63.0% reached blood-pressure targets at week 68 against 32.0% on placebo ^[13].

REDEFINE 5 compared CagriSema with semaglutide 2.4 mg alone in 331 adults in Japan and Taiwan with overweight or obesity and weight-related conditions. At 68 weeks the average weight change was −18.4% with CagriSema and −11.9% with semaglutide alone. Adverse events were reported by 87% and 84% respectively, mostly gastrointestinal, and 10% stopped CagriSema against 6% who stopped semaglutide. About a quarter of participants had type 2 diabetes ^[14]. This is one of the few direct comparisons showing what cagrilintide added to semaglutide in phase 3.

Novo Nordisk’s announcement reported that 5.9% stopped CagriSema because of adverse events against 3.5% on placebo in REDEFINE 1, and 8.4% against 3% in REDEFINE 2. It also reported nausea in 55% against 12.6%, constipation in 30.7% against 11.6% and vomiting in 26.1% against 4.1% in REDEFINE 1 ^[7].

The REIMAGINE programme tests CagriSema for blood-glucose control. REIMAGINE 1 enrolled 189 adults with type 2 diabetes managed by diet and exercise. Over 40 weeks HbA1c fell by 1.8 percentage points on CagriSema 2.4 mg/2.4 mg and 1.5 on 1.0 mg/1.0 mg, against 0.1 on placebo, and body weight fell by 13.8% and 11.8% against 1.4%. Adverse events, mostly mild or moderate and gastrointestinal, were reported by 79%, 75% and 66% ^[15].

REIMAGINE 2 is the largest, with 2,713 people with type 2 diabetes on metformin, with or without an SGLT2 inhibitor. Over 68 weeks, CagriSema 2.4 mg/2.4 mg lowered HbA1c by 1.91 percentage points against 1.75 with semaglutide 2.4 mg alone, a statistically significant difference. The trial ran in 30 countries and had seven groups, including CagriSema at 1.0 mg of each drug, semaglutide 1.0 mg, placebo and a cagrilintide 2.4 mg-only arm of 152 people ^[16].

REIMAGINE 3 added CagriSema or placebo to basal insulin in 274 adults. HbA1c fell by 2.33 and 2.10 percentage points on the two CagriSema doses against 0.66 on placebo at 40 weeks, body weight also fell, and no severe hypoglycaemia was reported. Adverse events were reported by 80% and 71% on the two CagriSema doses and 71% on placebo; one death, from cancer, was judged unrelated to treatment ^[17].

The benefits measured in trials are weight reduction, lower HbA1c in type 2 diabetes and, as a secondary outcome, lower blood pressure ^{[3] [5] [13] [15]}. Most of these results are for CagriSema. For cagrilintide alone, the evidence is weight loss of up to 10.8% at 26 weeks in phase 2 ^[3], and an HbA1c fall of 0.9 percentage points with 8.1% weight loss at 32 weeks in a small diabetes trial ^[4].

The trials measured results at fixed points rather than onset. In the phase 1b study, where cagrilintide was added to semaglutide 2.4 mg, weight change at week 20 was −15.7% with cagrilintide 1.2 mg and −17.1% with 2.4 mg, against −9.8% with semaglutide plus placebo ^[2]. The phase 2 trial of cagrilintide alone reported its results at 26 weeks ^[3], and the REDEFINE trials at 68 weeks ^{[5] [6]}.

With a half-life of roughly a week ^[2], blood levels build up over several weekly doses, and the trials also stepped the dose up gradually. The phase 1b study increased the doses at 4-week intervals over 16 weeks ^[2].

Unusually for a peptide sold on research sites, cagrilintide has been given to thousands of people in randomised trials, most of them published in The Lancet and the New England Journal of Medicine ^{[3] [5] [6]}. Almost all of the large trials tested the CagriSema combination rather than cagrilintide alone, so the evidence for cagrilintide by itself rests mainly on the 26-week phase 2 trial ^[3].

The phase 2 monotherapy trial tested 0.3, 0.6, 1.2, 2.4 and 4.5 mg by subcutaneous injection once weekly, after a dose-escalation period of up to six weeks ^[3]. The phase 1b study tested 0.16 mg to 4.5 mg weekly alongside semaglutide 2.4 mg, escalating over 16 weeks ^[2]. The phase 3 CagriSema trials used cagrilintide 2.4 mg with semaglutide 2.4 mg once weekly ^{[5] [6]}.

Laid out as a cagrilintide dosage chart from the trials: 0.3 to 4.5 mg weekly alone in phase 2 ^[3]; up to 4.5 mg weekly in a heart-rhythm (QT) study in healthy volunteers ^[11]; 1.0 mg or 2.4 mg weekly, each paired with the same dose of semaglutide, in the REIMAGINE diabetes trials ^{[15] [16]}; and single doses of 0.6 or 0.9 mg in kidney and liver impairment studies ^[12]. The highest cagrilintide dose we found tested in people is 4.5 mg weekly. There is no approved cagrilintide dosage, because there is no approved product.

These figures come from trials of Novo Nordisk’s investigational product and are reported for information only, not as a recommendation. Research powders sold online have not been shown to match them.

Research cagrilintide is usually sold as a powder in vials labelled 5 mg or 10 mg, so questions about units are questions about concentration. This is arithmetic only, not a dose or protocol. A 5 mg vial mixed with 2 mL of liquid would be 2.5 mg per mL; a 10 mg vial mixed with 2 mL would be 5 mg per mL. On a U-100 insulin syringe, 100 units equal 1 mL, so 10 units are 0.1 mL, which would contain 0.25 mg at 2.5 mg per mL or 0.5 mg at 5 mg per mL.

These sums only hold if the vial contains what the label says, which has not been shown for research cagrilintide. Our peptide calculator does the arithmetic for any vial and volume, and the bacteriostatic water guide covers the diluent.

In the phase 2 trial the most frequent adverse events were gastrointestinal (nausea, constipation and diarrhoea) and injection-site reactions. Nausea affected 20% to 47% of participants on cagrilintide depending on dose, against 18% on placebo ^[3]. In REDEFINE 1, gastrointestinal adverse events were reported by 79.6% of people on CagriSema against 39.9% on placebo; most were transient and mild to moderate ^[5]. Long-term safety of cagrilintide alone has not been established in a phase 3 trial.

Cagrilintide side effects have also been examined in dedicated safety studies. In a thorough QT study of 105 healthy volunteers, cagrilintide escalated to 4.5 mg did not cause clinically relevant prolongation of the QT interval on the heart tracing. The study used moxifloxacin, a drug known to lengthen the QT interval, to confirm that the method could detect an effect ^[11]. Two studies of single doses in 65 people with normal or impaired kidney or liver function found similar drug exposure across groups, with no consistent pattern by severity and no serious adverse events. Compared with normal kidney function, average exposure was about 1.2 times higher in mild, moderate and severe impairment, with wide confidence intervals; liver impairment made little difference ^[12]. In REIMAGINE 2, adverse events were reported by 82.2% of people on cagrilintide 2.4 mg alone, 86.9% on CagriSema and 70.5% on placebo, most often gastrointestinal ^[16].

The published abstracts we reviewed for cagrilintide do not report fatigue or hair loss rates. For comparison, a different amylin drug, eloralintide, reported fatigue as one of its most common adverse events in a 48-week trial ^[19], but that finding cannot be assumed to apply to cagrilintide.

Cagrilintide vs semaglutide compares two different hormone systems: amylin for cagrilintide and GLP-1 for semaglutide. Both are once-weekly injections, and most of the cagrilintide programme uses them together.

In the 32-week phase 2 diabetes trial, semaglutide alone lowered HbA1c more than cagrilintide alone (1.8 against 0.9 percentage points), while cagrilintide alone produced more weight loss than semaglutide alone (8.1% against 5.1%); the combination did better than either on both measures ^[4]. Time spent in the target glucose range rose to 88.9% on CagriSema, 76.2% on semaglutide and 71.7% on cagrilintide, and adverse events were reported by 68%, 71% and 80% respectively. The trial had 92 participants, so these single-agent comparisons are imprecise. In REDEFINE 5, adding cagrilintide to semaglutide increased average weight loss from 11.9% to 18.4% at 68 weeks ^[14].

Searches for cagrilintide and tirzepatide, or cagrilintide and retatrutide, often ask about stacks and combined dosage. We found no published trial that has given cagrilintide together with tirzepatide or with retatrutide, and no registered trial of either combination. There is therefore no studied dose for either combination.

What has been studied is CagriSema compared with tirzepatide. One trial randomised 809 adults with obesity to CagriSema 2.4 mg/2.4 mg or tirzepatide 15 mg, with the main result at week 84; it was completed in December 2025 ^[21]. A second compared the two in 1,024 people with type 2 diabetes over 68 weeks and was completed in March 2026 ^[22]. When we checked the registry, neither had posted results.

The FDA states that cagrilintide is not a component of any FDA-approved drug and cannot be used in compounding under federal law ^[20]. See the US legal status page.

Cagrilintide and retatrutide work in different ways. Cagrilintide acts on amylin and calcitonin receptors ^[10]; retatrutide acts on GIP, GLP-1 and glucagon receptors ^[23]. Both are investigational. They have not been compared in any trial.

The results that exist come from separate trials: cagrilintide alone produced up to 10.8% weight loss at 26 weeks ^[3], CagriSema produced 20.4% at 68 weeks ^[5], and retatrutide 12 mg produced 24.2% at 48 weeks in a phase 2 trial ^[23]. Different populations, durations and analysis methods make these figures unsuitable for a direct comparison.

Several companies are developing amylin-based drugs. Eloralintide, from Eli Lilly, is described as a selective amylin receptor agonist, whereas cagrilintide also activates the calcitonin receptor ^{[10] [19]}. In a 48-week phase 2 trial of 263 adults with obesity or overweight, eloralintide produced average weight changes from −9% on 1 mg to −20% on 9 mg, against −0.4% on placebo. Nausea and fatigue were the most common adverse events: nausea affected 11% to 64% depending on dose against 14% on placebo, and fatigue 0% to 46% against 12% ^[19]. Eloralintide and cagrilintide have not been compared head-to-head.

Amycretin, from Novo Nordisk, is a single molecule that acts on both GLP-1 and amylin receptors. In a phase 1b/2a study, weekly injections produced weight changes of −24.3% on 60 mg against −1.1% on placebo at 36 weeks, and −22.0% on 20 mg against +1.9% over the same period. Side effects were mostly mild to moderate and gastrointestinal, and many participants withdrew, often for reasons the authors judged unrelated to adverse events ^[18]. Pramlintide remains the only amylin analogue in clinical use, for diabetes ^[8].

As of September 2026, cagrilintide is not approved as a medicine anywhere we could confirm, either alone or as CagriSema. Novo Nordisk has reportedly submitted a New Drug Application to the FDA for CagriSema (cagrilintide 2.4 mg with semaglutide 2.4 mg) for weight management ^[7]. That information comes from the company, and we could not confirm a filing or an FDA decision from an FDA source as of September 2026.

The FDA’s current position on the ingredient is clear: cagrilintide has not been found safe and effective, is not a component of an approved drug, and cannot be used in compounding under federal law ^[20].

Research-grade cagrilintide is unlicensed, and its legal position differs by country; see our legal status pages and the UK legal status page.

Research cagrilintide is sold as a freeze-dried powder. General practice is to keep it cold, dry and away from light and to refrigerate it after reconstitution. See how to store peptides.

No manufacturer storage label for cagrilintide is public, because no product is approved. The cagrilintide half life of about 159 to 195 hours was measured in the phase 1b study ^[2], which is why the trials use once-weekly injections.

PepFinder does not sell cagrilintide. You can compare prices, read how to read a COA, and check third-party tested suppliers. Listings for cagrilintide UK prices are research-labelled material, not Novo Nordisk’s trial product.

No published study has tested the content of research cagrilintide that we could find. Our guides to third-party peptide testing and spotting a fake peptide supplier explain what an independent test should show.