Cagrilintide: The Amylin Analogue Guide

Key takeaways

Cagrilintide is a long-acting analogue of amylin, a pancreatic hormone that signals fullness after meals
In a Phase 2 trial of 706 participants, cagrilintide 4.5 mg produced 10.8% body weight loss over 26 weeks [1]
It outperformed liraglutide 3.0 mg in the same trial (10.8% vs 9.0%, P = 0.03) [1]
Cagrilintide is also half of CagriSema, a combination with semaglutide that produced 20.4% weight loss in Phase 3 [2]
It’s administered as a once-weekly subcutaneous injection
Cagrilintide is not yet FDA-approved as a standalone treatment

Amylin is a 37-amino acid hormone released by pancreatic beta cells alongside insulin after meals. It slows gastric emptying, suppresses glucagon secretion, and signals satiety in the brain. If that sounds similar to what GLP-1 drugs do, you’re right. But amylin acts through a completely different receptor system [3].

The problem with natural amylin is that it forms clumps (aggregates) quickly, making it impractical as a drug. Pramlintide (Symlin), an older amylin analogue, solved this partially but required three daily injections and produced only modest weight loss [3].

Cagrilintide (developed by Novo Nordisk) is a second-generation amylin analogue designed with two advantages: it doesn’t aggregate, and it lasts long enough for once-weekly dosing. It binds to both amylin receptors (AMY1R and AMY3R) and calcitonin receptors, which appears to be important for its weight loss effects [4].

A 2025 study in EBioMedicine confirmed that cagrilintide lowers body weight specifically through brain AMY1 and AMY3 receptors, which control satiety and food intake [5].

How cagrilintide works

Cagrilintide acts through a mechanism that’s related to but distinct from GLP-1 receptor agonists like semaglutide.

Satiety signaling. Amylin receptors in the area postrema and nucleus of the solitary tract (brain regions that process fullness signals) respond to cagrilintide by reducing meal size and frequency. You eat less per sitting and feel less compelled to eat between meals [3].

Gastric emptying. Like GLP-1 drugs, cagrilintide slows the rate at which food leaves your stomach. This extends the feeling of fullness after eating [3].

Glucagon suppression. Cagrilintide reduces post-meal glucagon secretion, which helps control blood sugar spikes. This is particularly relevant for patients with type 2 diabetes [1].

Preserved energy expenditure. Animal data from a 2025 Nature Metabolism study showed that cagrilintide (as part of CagriSema) reduced energy intake without the compensatory decrease in energy expenditure that often accompanies weight loss [6]. This is meaningful because metabolic slowdown is one of the main reasons weight loss plateaus.

The receptor pharmacology is complex. A 2025 study in Nature Communications mapped the structural and dynamic features of cagrilintide binding, showing it activates both calcitonin and amylin receptors through a unique binding mode [7]. This dual receptor activation may explain why cagrilintide produces greater weight loss than older amylin analogues that targeted fewer receptor subtypes.

Why amylin matters alongside GLP-1

You might wonder why another satiety hormone matters when GLP-1 drugs already work so well. The answer is complementary pathways.

GLP-1 and amylin activate different receptor populations in the brain. When you combine them, the appetite-suppressing effects appear to be additive. A Phase 1b trial demonstrated this directly: co-administered cagrilintide 2.4 mg and semaglutide 2.4 mg produced greater weight loss than either drug alone [8].

Think of it like this: GLP-1 tells one part of the brain you’re full. Amylin tells a different part. Activating both pathways simultaneously produces a stronger signal than either one alone.

This is the rationale behind CagriSema, which combines both drugs in a single weekly injection and produced 20.4% weight loss in the REDEFINE 1 Phase 3 trial [2].

For a broader view of how different peptides work for weight loss, see our pillar guide.

Phase 2 clinical trial results

The definitive Phase 2 trial for cagrilintide was published in The Lancet in December 2021 by Lau and colleagues [1].

Study design

The trial enrolled 706 adults without diabetes who had obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity. It was conducted at 57 sites across 10 countries [1].

Participants were randomized to one of seven groups:

Cagrilintide 0.3 mg weekly (n=100)
Cagrilintide 0.6 mg weekly (n=101)
Cagrilintide 1.2 mg weekly (n=100)
Cagrilintide 2.4 mg weekly (n=102)
Cagrilintide 4.5 mg weekly (n=102)
Liraglutide 3.0 mg daily (active control, n=99)
Placebo (pooled across groups, n=101)

Treatment lasted 26 weeks, including a dose-escalation period of up to 6 weeks [1].

Weight loss results

Group	Weight loss (trial product estimand)	Weight loss (kg)
Placebo	3.0%	3.3 kg
Cagrilintide 0.3 mg	6.0%	6.4 kg
Cagrilintide 0.6 mg	6.4%	6.8 kg
Cagrilintide 1.2 mg	6.9%	7.4 kg
Cagrilintide 2.4 mg	9.1%	9.7 kg
Cagrilintide 4.5 mg	10.8%	11.5 kg
Liraglutide 3.0 mg	9.0%	9.6 kg

All cagrilintide doses significantly outperformed placebo (P < 0.001). The 4.5 mg dose beat liraglutide 3.0 mg by 1.8 percentage points (P = 0.03) [1].

The dose-response relationship was clear: more drug, more weight loss, with no plateau at the highest tested dose. This suggests even higher doses might produce greater effects, though side effects would need monitoring.

Discontinuation rate

Only 10% of participants permanently discontinued treatment, and this was similar across groups. About 4% discontinued due to adverse events, with 4% withdrawing from the trial entirely [1]. These are low numbers for a weight loss trial.

Side effects

The side effect profile of cagrilintide is similar to GLP-1 drugs, which makes sense given the overlapping mechanism on gastric emptying.

Gastrointestinal events were the most common adverse effects. Nausea occurred in 20-47% of cagrilintide-treated patients (dose-dependent) versus 18% on placebo. Constipation and diarrhea were also reported [1].

However, a meta-analysis comparing cagrilintide to semaglutide and liraglutide found that vomiting was significantly lower with cagrilintide alone than with GLP-1 agonists [9]. This suggests the GI profile may be somewhat more tolerable than semaglutide.

Injection site reactions occurred more frequently with cagrilintide than placebo but were generally mild [1].

No significant cardiovascular signals emerged in the Phase 2 data, though the trial wasn’t powered to detect rare cardiovascular events.

For a broader look at peptide side effects, including GLP-1 drugs, see our overview guide.

Cagrilintide vs. other weight loss drugs

vs. semaglutide (Wegovy)

Cagrilintide 4.5 mg produced 10.8% weight loss in 26 weeks [1]. Semaglutide 2.4 mg produced approximately 14.9% weight loss in 68 weeks in the STEP 1 trial. The trial designs and durations differ, making direct comparison difficult. What’s clearer: the two drugs work on different receptor systems, which is why combining them (as CagriSema) produces additive effects [2].

vs. tirzepatide (Zepbound)

Tirzepatide targets both GLP-1 and GIP receptors and produced up to 22.5% weight loss at 72 weeks. As a standalone agent, cagrilintide doesn’t match this. But combined with semaglutide as CagriSema, the 20.4% weight loss at 68 weeks is in a similar range [2]. See our semaglutide vs tirzepatide comparison for more on these drugs.

vs. pramlintide (Symlin)

Pramlintide is the only FDA-approved amylin analogue, but it’s approved for diabetes management, not weight loss. It requires three daily injections and produces only 1-2 kg of weight loss. Cagrilintide’s once-weekly dosing and substantially greater weight loss represent a generational improvement [3].

vs. tesofensine

Tesofensine works through a completely different mechanism (triple monoamine reuptake inhibition). Its Phase 2 data showed 11.2% weight loss at 0.5 mg over 24 weeks. The weight loss is similar to cagrilintide 4.5 mg, but the side effect profiles are different: tesofensine causes dry mouth, insomnia, and heart rate elevation, while cagrilintide causes more GI effects [1].

Current development status

Cagrilintide is being developed primarily as part of CagriSema (with semaglutide), which has completed Phase 3 trials (REDEFINE 1 and REDEFINE 2) [2, 10]. Novo Nordisk has submitted CagriSema for FDA review.

As a standalone agent, cagrilintide is not currently in late-stage development for obesity. The company’s strategy focuses on the combination product, where the additive effects of amylin + GLP-1 receptor agonism produce substantially greater weight loss than either component alone.

Other companies are developing their own amylin analogues, including eloralintide, petrelintide, and AZD6234. A 2026 review in Peptides noted that several of these have shown strong efficacy as monotherapy in clinical trials [3].

How to access amylin-based treatments

Cagrilintide is not available as a standalone prescription. It is not sold by pharmacies or compounding pharmacies.

CagriSema (the combination with semaglutide) is expected to receive an FDA decision in 2026. If approved, it would be available by prescription.

For patients interested in available weight loss treatments today, GLP-1 receptor agonists like semaglutide and tirzepatide are the closest alternatives. Both are available through online prescriptions from licensed telehealth providers.

Frequently asked questions

Is cagrilintide the same as pramlintide?▼

No. Both are amylin analogues, but they’re different molecules with different properties. Pramlintide (Symlin) requires three daily injections and is approved only for diabetes. Cagrilintide is a next-generation analogue designed for once-weekly dosing with significantly greater weight loss [1, 3].

Is cagrilintide a peptide?▼

Yes. Cagrilintide is a modified peptide based on the structure of human amylin (also called islet amyloid polypeptide, or IAPP). It’s been engineered with amino acid substitutions that prevent aggregation and extend its half-life, allowing weekly dosing [3].

Can I get cagrilintide now?▼

Not as a standalone product. Cagrilintide is only available as part of CagriSema (in combination with semaglutide), which is under FDA review as of 2026. If you’re interested in peptide-based weight loss treatment, see our guide on how to get peptides prescribed.

How does cagrilintide compare to Ozempic?▼

Ozempic (semaglutide 1.0 mg) is approved for type 2 diabetes, not obesity. In terms of weight loss, cagrilintide 4.5 mg and semaglutide 2.4 mg produce broadly similar results. The real story is what happens when you combine them: CagriSema produced 20.4% weight loss in the REDEFINE 1 trial, significantly more than either drug alone [2].

What are the main side effects of cagrilintide?▼

Nausea (20-47% depending on dose), constipation, diarrhea, and injection site reactions. The GI effects are similar to GLP-1 drugs but vomiting appears less common with cagrilintide than with semaglutide or liraglutide [1, 9].

Why is Novo Nordisk combining cagrilintide with semaglutide instead of selling it alone?▼

The combination produces substantially more weight loss (20.4%) than either drug alone [2]. By combining two complementary mechanisms in a single injection, Novo Nordisk can offer a product that competes with tirzepatide’s 22.5% weight loss. The standalone amylin analogue market may develop later as other companies bring their own analogues forward [3].

Does cagrilintide work for type 2 diabetes?▼

The REDEFINE 2 trial tested CagriSema in patients with type 2 diabetes and found 13.7% weight loss plus significant improvements in glycated hemoglobin (73.5% of patients reached HbA1c ≤6.5%) [10]. Cagrilintide alone suppresses post-meal glucagon, which helps with blood sugar control, but its diabetes efficacy has primarily been studied in combination with semaglutide.

Is cagrilintide available through compounding pharmacies?▼

No. Cagrilintide is not an FDA-approved ingredient and cannot be legally compounded. For information on compounded weight loss medications, see our guide on compounding pharmacy peptides.

References

Lau DCW, Erichsen L, Francisco AM, et al. 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. Lancet. 2021;398(10317):2160-2172. https://pubmed.ncbi.nlm.nih.gov/34798060/
Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity. N Engl J Med. 2025;393(7):635-647. https://pubmed.ncbi.nlm.nih.gov/40544433/
Bailey CJ, Flatt PR, Conlon JM. Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes. Peptides. 2026;177:171480. https://pubmed.ncbi.nlm.nih.gov/41747885/
Liang YL, et al. Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors. Nat Commun. 2025;16(1):3408. https://pubmed.ncbi.nlm.nih.gov/40204768/
Larsen AT, et al. Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine. 2025;108:105324. https://pubmed.ncbi.nlm.nih.gov/40609154/
CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure. Nat Metab. 2025;7(7):1301-1314. https://pubmed.ncbi.nlm.nih.gov/40629149/
Liang YL, et al. Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors. Nat Commun. 2025;16(1):3408. https://pubmed.ncbi.nlm.nih.gov/40204768/
Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021;397(10286):1736-1748. https://pubmed.ncbi.nlm.nih.gov/33894838/
Dutta D, Nagendra L, Harish BG, et al. Efficacy and safety of cagrilintide alone and in combination with semaglutide (Cagrisema) as anti-obesity medications: a systematic review and meta-analysis. Indian J Endocrinol Metab. 2024;28(5):436-444. https://pubmed.ncbi.nlm.nih.gov/39676787/
Davies MJ, Bajaj HS, Broholm C, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes. N Engl J Med. 2025;393(7):648-659. https://pubmed.ncbi.nlm.nih.gov/40544432/