Editorial note: this article summarises published research on cagrilintide and CagriSema. Baclabs does not sell cagrilintide, semaglutide or any peptide; we supply bacteriostatic water and reconstitution consumables. Nothing here is medical advice.
Cagrilintide is a long-acting analogue of amylin, a hormone the pancreas releases alongside insulin after a meal. It is the first amylin agonist to reach phase 3 for obesity, and it does so in combination: CagriSema is cagrilintide 2.4 mg co-administered with semaglutide 2.4 mg once weekly. In the phase 3 REDEFINE 1 trial, CagriSema produced 20.4% mean weight loss at 68 weeks, against 14.9% for semaglutide alone and 11.5% for cagrilintide alone [1].
The interest in cagrilintide is mechanistic as much as numerical. Every other compound in the GLP-1 peptides guide works through incretin receptors. Amylin uses a separate pathway, which is why adding it to semaglutide yields more weight loss than either alone. This article explains that pathway, sets out the cagrilintide monotherapy data, reviews REDEFINE 1 and 2, and covers the adverse-effect profile and regulatory status. Neither cagrilintide nor CagriSema is licensed anywhere as of September 2026.
What amylin does
Amylin, also called islet amyloid polypeptide, is a 37-amino-acid peptide co-secreted with insulin by pancreatic beta cells. It acts on the area postrema, a region of the hindbrain that sits outside the blood-brain barrier, to reduce food intake, slow gastric emptying and suppress post-meal glucagon secretion [2]. Its receptor is a complex of the calcitonin receptor with a receptor activity-modifying protein (RAMP), which is why some amylin analogues also show calcitonin-receptor activity.
Native amylin is unusable as a drug for two reasons. It has a half-life of minutes, and human amylin aggregates into amyloid fibrils, the same deposits found in the pancreatic islets of people with type 2 diabetes. Pramlintide, an older amylin analogue licensed in the US for diabetes, solved the aggregation problem but still requires injection before each meal. Cagrilintide adds a fatty acid chain that binds albumin, extending the half-life enough for once-weekly dosing.
Amylin and GLP-1 act on different neurons and different signalling cascades. GLP-1 agonists reduce appetite mainly through the hypothalamus and brainstem GLP-1 receptors; amylin’s satiety signal originates in the area postrema and connects to the same downstream circuits. Combining them adds a second input rather than turning up the first, which in principle should give more effect at the same GLP-1 dose and the same GLP-1-driven side effects. Amylin has also been reported to preserve bone mass, an effect not seen with GLP-1 agonists [2].
Cagrilintide alone: the phase 2 data
The dose-finding phase 2 trial, published in The Lancet in 2021, randomised 706 adults with overweight or obesity across 57 sites to once-weekly cagrilintide 0.3, 0.6, 1.2, 2.4 or 4.5 mg, once-daily liraglutide 3.0 mg or placebo for 26 weeks [3]. Weight loss was dose-dependent:
| Arm (26 weeks) | Mean weight change |
|---|---|
| Placebo | −3.0% |
| Cagrilintide 0.3–4.5 mg | −6.0% to −10.8% (dose-dependent) |
| Cagrilintide 4.5 mg | −10.8% |
| Liraglutide 3.0 mg daily | −9.0% |
Cagrilintide 4.5 mg beat liraglutide by 1.8 percentage points (p=0.03). Gastrointestinal events occurred in 41–63% of cagrilintide recipients versus 32% on placebo, mostly nausea, with administration-site reactions the other common finding [3]. These are trial doses reported for context; no licensed dose exists.
CagriSema: cagrilintide + semaglutide in REDEFINE 1 and 2
REDEFINE 1 was a 68-week, double-blind phase 3 trial in 3,417 adults with obesity, or overweight with at least one comorbidity, without type 2 diabetes. Participants were randomised 21:3:3:7 to CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg), semaglutide 2.4 mg alone, cagrilintide 2.4 mg alone or placebo, each once weekly with lifestyle intervention [1][4]. The treatment-policy estimand, which counts everyone regardless of whether they stayed on treatment, gave:
| Arm (68 weeks) | N | Mean weight change |
|---|---|---|
| CagriSema 2.4 mg / 2.4 mg | 2,108 | −20.4% |
| Semaglutide 2.4 mg | 302 | −14.9% |
| Cagrilintide 2.4 mg | 302 | −11.5% |
| Placebo | 705 | −3.0% |
Under the trial-product estimand, which models the effect if everyone had adhered, CagriSema reached −22.7% versus −2.3% for placebo; 40.4% of CagriSema participants lost at least 25% of body weight and 23.1% lost at least 30% [5]. Roughly half of CagriSema participants (50.7%) moved out of the obesity BMI range compared with 10.2% on placebo [6].
REDEFINE 2 tested CagriSema against placebo in 1,206 adults with type 2 diabetes and obesity. Mean weight change at 68 weeks was −13.7% versus −3.4%, and 73.5% of CagriSema participants reached an HbA1c of 6.5% or below compared with 15.9% on placebo [4][6]. As with every incretin-based drug, weight loss is smaller in people with diabetes.
Two caveats are worth stating. CagriSema’s 20.4% at 68 weeks is close to the 20.2% at 72 weeks that tirzepatide achieved in SURMOUNT-5, but the two have not been compared head-to-head and the trials differ in design; see the tirzepatide vs semaglutide article. Second, the semaglutide arm’s 14.9% is consistent with STEP 1, which lends the comparison credibility but also shows that most of CagriSema’s effect is semaglutide’s.
Adverse effects
Gastrointestinal events were reported by 79.6% of CagriSema participants versus 39.9% on placebo in REDEFINE 1, with nausea in 55% versus 12.6% [5]. Most were mild to moderate and transient. Discontinuation because of adverse events was 5.9% with CagriSema, 3.6% with semaglutide, 2.6% with cagrilintide and 3.5% with placebo [1]. Cagrilintide’s own contribution to the side-effect burden is therefore modest, and the combination adds a little over semaglutide alone.
Because CagriSema contains semaglutide at its full licensed dose, every semaglutide warning applies: acute pancreatitis, for which the Medicines and Healthcare products Regulatory Agency (MHRA) strengthened class-wide warnings in January 2026 [7]; gallbladder disease; diabetic retinopathy; and the rodent thyroid C-cell finding that underpins the US boxed warning [8]. What long-term amylin agonism adds has not been characterised beyond trial duration.
Regulatory status and what is sold as cagrilintide
Novo Nordisk published REDEFINE 1 and 2 in the New England Journal of Medicine in June 2025 [1][6]. Neither cagrilintide nor CagriSema holds a marketing authorisation in the UK, the EU or the US as of September 2026. Any vial sold as cagrilintide, or any “CagriSema” kit, is therefore either an unlicensed medicine or a research chemical of unverified content. The MHRA seized unlicensed peptide products alongside retatrutide and tirzepatide in enforcement operations in October 2025 and May 2026 [9]. The retatrutide article discusses how to read a certificate of analysis for any grey-market peptide.
Reconstitution notes
In the trials, cagrilintide and semaglutide were given as separate pre-filled injections or a fixed-dose combination pen prepared by the sponsor. Grey-market cagrilintide is a lyophilised powder, commonly 5 or 10 mg. The concentration arithmetic is the same as for any peptide: milligrams in the vial divided by millilitres of diluent. A 5 mg vial with 2 mL of bacteriostatic water gives 2.5 mg/mL, or 25 mcg per unit on a U-100 insulin syringe; a 10 mg vial with 2 mL gives 5 mg/mL and 50 mcg per unit. A vial drawn from over several weeks needs a preserved diluent, and an opened multi-dose vial is conventionally discarded after 28 days; see the storage and shelf-life guide.
Multi-dose vials need a preserved diluent. Baclabs supplies UK-stocked bacteriostatic water in 30 mL vials; see the reconstitution guide for the general method and the GLP-1 reconstitution protocols article for full dose tables.
Frequently asked questions
What is cagrilintide?
Cagrilintide is an investigational once-weekly analogue of amylin, a pancreatic hormone that reduces food intake and slows gastric emptying by acting on the area postrema in the hindbrain. In a 26-week phase 2 trial, 4.5 mg weekly produced 10.8% weight loss, more than liraglutide 3.0 mg daily [3]. It is being developed by Novo Nordisk.
What is CagriSema?
CagriSema is a fixed combination of cagrilintide 2.4 mg and semaglutide 2.4 mg given once weekly. In the 68-week REDEFINE 1 trial it produced 20.4% mean weight loss, compared with 14.9% for semaglutide alone, 11.5% for cagrilintide alone and 3.0% for placebo [1]. It is not licensed in any country as of September 2026.
How does amylin differ from GLP-1?
Both reduce appetite and slow gastric emptying, but through separate receptors and brain regions. GLP-1 acts largely on hypothalamic and brainstem GLP-1 receptors and boosts insulin secretion; amylin acts on calcitonin-receptor complexes in the area postrema and suppresses glucagon [2]. Because the pathways are distinct, combining them adds effect rather than duplicating it.
Is cagrilintide better than semaglutide?
Not on its own. In REDEFINE 1, cagrilintide 2.4 mg alone gave 11.5% weight loss versus 14.9% for semaglutide 2.4 mg [1]. Its value is as an add-on: the combination reached 20.4%. Cagrilintide alone caused fewer discontinuations for adverse events (2.6% versus 3.6%), suggesting it is somewhat better tolerated.
What are the side effects of CagriSema?
Mainly gastrointestinal: nausea in 55% of participants, with vomiting, diarrhoea and constipation also common, mostly mild and transient [5]. Discontinuation for adverse events was 5.9%. Since CagriSema contains full-dose semaglutide, the pancreatitis, gallbladder and retinopathy warnings for semaglutide apply, and long-term effects of chronic amylin agonism are not yet characterised.
References
- Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1). Garvey WT et al., New England Journal of Medicine, 2025. doi:10.1056/NEJMoa2502081; PubMed 40544433
- ADA 2025: CagriSema Demonstrates Significant Weight Loss in REDEFINE Clinical Trials. Pharmacy Times, 2025
- Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lau DCW et al., The Lancet, 2021. doi:10.1016/S0140-6736(21)01751-7
- REDEFINE 1 and REDEFINE 2: Greater Weight Loss With Combined Cagrilintide-Semaglutide vs Either Drug Alone or Placebo. American College of Cardiology journal scan, 2025
- CagriSema 2.4 mg / 2.4 mg demonstrated 22.7% mean weight reduction in adults with overweight or obesity in REDEFINE 1, published in NEJM. Novo Nordisk press release, June 2025
- ADA 2025: CagriSema Demonstrates Dual Benefit in Obesity and Type 2 Diabetes (REDEFINE 2). HCPLive, 2025; Davies MJ et al., NEJM, doi:10.1056/NEJMoa2502082
- GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists: strengthened warnings on acute pancreatitis. MHRA Drug Safety Update, January 2026
- WEGOVY (semaglutide) injection, US Prescribing Information. FDA, 2025
- Two arrested during the MHRA’s largest ever seizure of unlicensed weight loss medicines. MHRA / GOV.UK, May 2026
Disclaimer: This content is for educational purposes only and does not constitute medical advice. Bacteriostatic water is supplied for reconstitution of substances intended for research and for use as directed by a healthcare professional. Peptides and medicines discussed here may be unlicensed in the UK or prescription-only; consult a qualified clinician before using any medicine. Baclabs does not sell peptides.