Fat Loss & Metabolic

Cagrilintide

Also known as AM833, NNC0174-0833, CagriSema (fixed-dose combination with semaglutide)

An investigational once-weekly injectable that copies the hormone amylin to reduce appetite, studied mostly alongside semaglutide rather than on its own.

How it works

A long-acting analog of amylin that regulates satiety. Slows gastric emptying and signals the brain to feel full on a separate pathway than GLP-1.

Performance edge

Superior for long-term weight management; prevents the weight loss plateau when combined with Tirzepatide.

Plain-English guide

Cagrilintide, without the jargon

What it is

Cagrilintide is a laboratory-made copy of amylin, a hormone your pancreas releases alongside insulin every time you eat. Natural amylin breaks down within minutes, so chemists attached a long fatty acid chain to the peptide and swapped several amino acids, which stretches its half-life in the body to roughly 174 to 211 hours, long enough for one injection a week. It is still an investigational drug: it is being developed by Novo Nordisk mainly as one half of CagriSema, a single weekly shot that pairs cagrilintide with semaglutide, the GLP-1 (glucagon-like peptide-1) receptor agonist sold as Wegovy and Ozempic. Almost all of the large published human data comes from that combination rather than from cagrilintide used alone.

What people use it for

Reducing body weight in adults with overweight or obesity, usually combined with semaglutide
Reducing body weight and blood sugar in adults who also have type 2 diabetes
Lowering waist circumference and systolic blood pressure alongside weight loss
Adding a second appetite pathway when a GLP-1 drug alone has stopped producing further loss
Research use as a tool for studying amylin and calcitonin receptor biology

How it works, simply

Think of appetite as a house with two front doors. GLP-1 drugs knock loudly on one of them; amylin drugs like cagrilintide knock on the other. Cagrilintide tells a small patch of your hindbrain that food has arrived and slows the rate at which your stomach hands food on to the intestine, so the meal feels larger and lasts longer. Because the two drugs use different doors, opening both tends to quiet hunger more than pushing harder on either one.

What to expect, and when

Week 1Starting doses are deliberately low. Nausea, reduced appetite and injection-site redness were the earliest things trial participants noticed; weight change at this point is small.
Week 2-6Doses are stepped up gradually. Appetite suppression becomes more obvious and early weight loss appears, with gastrointestinal symptoms most common during each step up.
Week 8-20Maintenance dosing is usually reached. In the phase 3a REDEFINE 1 trial the weight curve was still falling steeply through this period.
Week 26The phase 2 monotherapy programme measured its main result at this point; the pooled meta-analysis put cagrilintide alone at about 6 percent of body weight lost versus comparator.
Week 68+REDEFINE 1 ran to week 68, where cagrilintide plus semaglutide averaged 20.4 percent weight loss versus 3.0 percent on placebo. Nothing published tells you what happens after stopping.

Side effects and interactions

Gastrointestinal events dominate: in REDEFINE 1 they affected 79.6 percent of the cagrilintide-semaglutide group versus 39.9 percent on placebo, and were mainly transient and mild to moderate
Nausea, vomiting, diarrhoea, constipation and abdominal pain
Reduced appetite, which is the intended effect but was recorded as an adverse event in the pharmacokinetic studies
Injection-site reactions, including erythema at the injection site
Serious adverse events were more frequent on the combination than on placebo in the phase 3 programme
The pooled meta-analysis found a modest overall increase in adverse events with cagrilintide (risk ratio 1.16) and a slight increase with CagriSema (risk ratio 1.06)

Who should avoid it

You are pregnant, trying to conceive or breastfeeding, since no human pregnancy data has been published for cagrilintide
You have a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, which is a standing contraindication for the semaglutide it is normally combined with
You have gastroparesis or another condition involving delayed gastric emptying, since slowing the stomach further is the mechanism of this drug
You have a history of pancreatitis, gallbladder disease or an eating disorder
You are already losing weight rapidly, are underweight, or cannot maintain adequate protein and fluid intake
You are not under the supervision of a physician who can monitor weight, blood sugar, hydration and any existing medications

Common mistakes

Starting at a maintenance dose instead of titrating. Every published trial stepped the dose up slowly, and the nausea rate tracked the size of each step
Reconstituting with the wrong diluent or shaking the vial. Bacteriostatic water added slowly down the vial wall, swirled rather than shaken, is the standard handling for lyophilised peptides
Storing the reconstituted vial at room temperature or leaving it in a car. Reconstituted peptide belongs refrigerated and protected from light
Stacking it on top of a GLP-1 drug that is already at a high dose without lowering anything. The two act on overlapping gastrointestinal pathways and the side-effect burden adds up
Ignoring protein intake and resistance training. The mouse data showed fat mass falling while lean mass was preserved, but no published human trial guarantees that outcome without training and adequate protein

Deep research

What the literature actually shows

Mechanism

Amylin is co-secreted with insulin from pancreatic beta cells at every meal. It acts on amylin receptors, which are built from the calcitonin receptor paired with one of three receptor activity-modifying proteins (RAMP1, RAMP2 or RAMP3) to give the AMY1, AMY2 and AMY3 receptor subtypes. Cagrilintide is a non-selective agonist at these receptors and at the calcitonin receptor itself, which is why it is often described as a dual amylin and calcitonin receptor agonist. Native amylin is cleared too fast to be a weekly drug, so cagrilintide was engineered with amino acid substitutions plus a fatty diacid side chain that binds albumin; the two dedicated pharmacokinetic studies published in Clinical Pharmacokinetics measured a terminal half-life of 174 to 211 hours.

The weight effect is centrally mediated. In the eBioMedicine mouse study, cagrilintide activated neurons in the area postrema, a hindbrain region that sits outside the blood-brain barrier and registers meal-related signals. Wild-type mice lost about 3.4 g of body weight over three weeks, and the loss came from fat mass while lean mass was preserved. In RAMP1/RAMP3 knockout mice the weight effect disappeared entirely, which identifies AMY1 and AMY3 as the receptors that matter. Salmon calcitonin, used as a comparator, activated more area postrema neurons yet increased weight in wild-type animals, so raw neuronal activation is not the whole story.

Peripherally, amylin signalling slows gastric emptying, so a given meal stays in the stomach longer and produces a longer-lasting sense of fullness. This is a different lever from the incretin effect of GLP-1 receptor agonists, which is the rationale for combining the two into a single weekly injection. The phase 3a REDEFINE 1 trial tested that logic directly by running cagrilintide alone, semaglutide alone, the combination and placebo in parallel, and the combination outperformed both single agents.

The combination also moves cardiometabolic markers beyond the scale. The pooled meta-analysis recorded a waist circumference reduction of 10.91 cm and a systolic blood pressure fall of 5.52 mm Hg with CagriSema, against 3.30 mm Hg with cagrilintide alone, and found a glycaemic benefit (HbA1c down 0.25 percent) only for the combination. That pattern is consistent with cagrilintide contributing appetite and weight effects while semaglutide supplies most of the direct glucose lowering.

Strength of evidence

Human trialsMultiple large randomised placebo-controlled human trials exist, including a 3,417-participant phase 3a trial with a cagrilintide monotherapy arm, but nearly all of the efficacy evidence describes cagrilintide combined with semaglutide rather than used alone.

Key studies

Randomised controlled trial2025New England Journal of Medicinen = 3417
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity
In this 68-week phase 3a double-blind trial (REDEFINE 1), cagrilintide-semaglutide reduced body weight by a mean of 20.4 percent versus 3.0 percent with placebo, with more participants reaching the 5, 20, 25 and 30 percent loss thresholds. Gastrointestinal adverse events occurred in 79.6 percent of the combination group versus 39.9 percent on placebo and were mainly transient and mild to moderate.
Randomised controlled trial2026Diabetes, Obesity and Metabolismn = 3417
Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1
Reanalysing the same phase 3a trial, 30.3 percent of the CagriSema group reached both a body mass index below 27 and a waist-to-height ratio below 0.53 at week 68, against 19.1 percent on semaglutide alone, 9.0 percent on cagrilintide alone and 3.3 percent on placebo. Among CagriSema participants who hit both targets, 61.3 percent met all four cardiometabolic outcomes measured.
Review2026Annals of Medicine and Surgeryn = 5425
Amylin-based obesity therapy: a meta-analysis of Cagrilintide and CagriSema versus placebo
Pooling four randomised controlled trials, cagrilintide monotherapy reduced body weight by 6.08 percent (5.89 kg) and CagriSema by 5.98 percent (4.68 kg) versus comparator, with waist circumference down 10.91 cm and systolic blood pressure down 5.52 mm Hg on CagriSema. Only CagriSema improved HbA1c, by 0.25 percent. Adverse events rose modestly with cagrilintide (risk ratio 1.16) and slightly with CagriSema (risk ratio 1.06).
Human trial2026Clinical Pharmacokineticsn = 65
Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide
Two open-label parallel-group studies (33 participants with varying kidney function, 32 with varying liver function) found cagrilintide exposure essentially unchanged across impairment categories and a terminal half-life of 174 to 211 hours. Treatment-emergent adverse events were injection-site erythema, nausea, vomiting and decreased appetite; none were serious and none led to withdrawal.
Animal study2025eBioMedicine
Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3
In mice, cagrilintide reduced body weight by about 3.4 g over three weeks and selectively cut fat mass while sparing lean mass. The effect was abolished in RAMP1/RAMP3 knockout animals, showing dependence on the AMY1 and AMY3 receptor subtypes, and was accompanied by activation of area postrema neurons in the hindbrain.
Review2025New England Journal of Medicine
Expanding the Treat-to-Target Toolbox for Obesity and Diabetes Care
This editorial summarises both phase 3 REDEFINE trials: body weight fell 20.4 percent versus 3.0 percent in REDEFINE 1 and 13.7 percent versus 3.4 percent in REDEFINE 2, where 73.5 percent of the combination group reached an HbA1c of 6.5 percent or lower against 15.9 percent on placebo. It also notes that gastrointestinal side effects and serious adverse events were more frequent with the combination.

Safety data

Tolerability is dominated by the gastrointestinal tract. In REDEFINE 1, 79.6 percent of participants on cagrilintide-semaglutide reported at least one gastrointestinal adverse event against 39.9 percent on placebo, spanning nausea, vomiting, diarrhoea, constipation and abdominal pain. The trial investigators describe these as mainly transient and mild to moderate, but the accompanying New England Journal of Medicine editorial notes that both gastrointestinal side effects and serious adverse events were more frequent on the combination than on placebo. The pooled meta-analysis of four trials found an overall adverse event risk ratio of 1.16 for cagrilintide and 1.06 for CagriSema.

Dedicated pharmacokinetic work in people with reduced kidney or liver function found no change in exposure and no serious treatment-emergent adverse events across 65 participants, and concluded that dose adjustment was unnecessary in those groups. Those were small, short, open-label studies, so they speak to how the drug is handled rather than to long-term risk. The commonly reported events there were injection-site erythema, nausea, vomiting and decreased appetite.

Two gaps matter. First, cagrilintide has not been approved by any regulator, so there is no label listing contraindications, no post-marketing surveillance database and no manufacturing standard for material sold outside the trial programme. Second, the published trials ran to 68 weeks with no follow-up data on weight regain, bone density or amylin receptor signalling after stopping, and the contraindications that apply to CagriSema as a product (history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2) come from the semaglutide component rather than from cagrilintide studies.

Regulatory status

FDA: As of 19 September 2026 cagrilintide has no FDA approval in any form; Novo Nordisk submitted a New Drug Application for the CagriSema fixed-dose combination in December 2025 and no decision has been published.
WADA: Cagrilintide is not named on the WADA 2026 Prohibited List, and the related GLP-1 receptor agonists semaglutide and tirzepatide sit on the WADA Monitoring Program rather than the prohibited list, so athletes should confirm current status with their anti-doping organisation before use.

Open questions

How much of the CagriSema weight loss is attributable to cagrilintide itself? The monotherapy arm of REDEFINE 1 lost markedly less than the combination, and no large standalone phase 3 trial of cagrilintide alone has been published.
What happens after week 68? There is no published data on weight maintenance, regain or rebound hunger once cagrilintide is stopped.
Does the pattern of losing fat while sparing lean mass seen in mice hold in humans over a year or more, and does resistance training change it?
Because cagrilintide also agonises the calcitonin receptor, what is the long-term effect on bone turnover and bone mineral density? A trial on cagrilintide and bone metabolism has been registered but no results are published.
Does the amylin pathway offer better tolerability than GLP-1 drugs at equivalent weight loss, as the amylin-analogue field argues, or does it simply add its own gastrointestinal burden on top?