Cagrilintide
clinical trialsAlso known as: AM833, NNC0174-0833
Cagrilintide (AM833, NNC0174-0833) is a long-acting acylated amylin analog designed to mimic the physiological effects of amylin, a pancreatic hormone that regulates satiety and gastric emptying. Its mechanism of action involves binding to amylin receptors in the area postrema and other central nervous system regions, leading to reduced food intake, delayed gastric emptying, and enhanced energy expenditure. The molecule's extended half-life is achieved through fatty acid acylation, enabling once-weekly subcutaneous administration. Key research findings from clinical trials demonstrate dose-dependent weight loss in individuals with overweight or obesity, with reductions of up to 10–15% body weight at higher doses over 26–52 weeks. Notably, the combination of cagrilintide with semaglutide (a GLP-1 receptor agonist), termed CagriSema, has shown synergistic effects, achieving greater weight loss than either agent alone in Phase 2 trials. Adverse effects are primarily gastrointestinal (nausea, vomiting, diarrhea), consistent with amylin receptor activation, and are generally dose-dependent and transient. Clinically, cagrilintide represents a novel therapeutic approach for obesity management, particularly as part of combination therapy targeting multiple appetite-regulating pathways. Its potential to enhance weight loss outcomes beyond existing GLP-1-based treatments is under investigation in Phase 3 trials, including cardiovascular outcomes studies. If approved, it could offer an additional option for patients with inadequate response to current monotherapies. For research purposes only — not medical advice.
Key data
C194H312N54O59S2Research & studies
Cagrilintide-semaglutide (2.4 mg each) was superior to semaglutide 2.4 mg for HbA1c reduction at week 68; Mean HbA1c change was -1.91 percentage points with cagrilintide-semaglutide vs -1.75 with semaglutide 2.4 mg; Adverse events occurred in 86.9% of the cagrilintide-semaglutide (2.4 mg each) group vs 81.2% with semaglutide 2.4 mg, most commonly gastrointestinal disorders; The safety profile was consistent with the GLP-1 receptor agonist class and prior cagrilintide data
Cagrilintide-semaglutide 2.4 mg each reduced HbA1c by 2.33% vs 0.66% for placebo (estimated treatment difference -1.68 percentage points, p<0.0001).; Cagrilintide-semaglutide 1.0 mg each reduced HbA1c by 2.10% vs 0.66% for placebo (estimated treatment difference -1.44 percentage points, p<0.0001).; Bodyweight reductions of 10-12% were observed with cagrilintide-semaglutide.; No severe hypoglycemia was reported; adverse events were mostly mild or moderate gastrointestinal disorders.
Eloralintide preferentially activates human AMY1R (12-fold > CTR, 11-fold > AMY3R) and induced less conditioned taste avoidance in rats than cagrilintide.; In diet-induced obese rats, eloralintide dose-dependently reduced food intake and lowered body weight primarily through fat mass loss.; In the phase 1 trial, single doses of 4 and 12 mg resulted in week-4 mean percent change from baseline in body weight of -2.5% (p < 0.01) and -4.4% (p < 0.001) vs placebo (+0.6%).; Eloralintide showed favorable pharmacokinetics supporting once-weekly dosing, with most adverse events being mild (15/16) and only one moderate vomiting event.
Cagrilintide-semaglutide resulted in a mean 20.4% body weight reduction vs 3.0% with placebo.; Participants on the combination were significantly more likely to achieve ≥5%, ≥20%, ≥25%, and ≥30% weight loss.; Gastrointestinal adverse events occurred in 79.6% of the combination group vs 39.9% with placebo, mostly transient and mild-to-moderate.
Mean body weight change from baseline to week 68 was -13.7% with cagrilintide-semaglutide vs -3.4% with placebo (difference -10.4 percentage points, P<0.001).; Significantly more patients in the cagrilintide-semaglutide group achieved weight reductions of ≥5%, ≥10%, ≥15%, and ≥20% (P<0.001 for all).; Glycated hemoglobin level ≤6.5% was achieved by 73.5% of patients in the cagrilintide-semaglutide group vs 15.9% in the placebo group.; Gastrointestinal adverse events occurred in 72.5% of the cagrilintide-semaglutide group vs 34.4% of the placebo group, mostly transient and mild to moderate.
Cagrilintide reduced body weight by 3.4 g in wild-type mice but not in RAMP1/3 knockout mice.; Both cagrilintide and salmon calcitonin decreased food intake only in wild-type mice during early treatment.; Cagrilintide activated cFos in the dorsal vagal complex and lateral parabrachial nucleus of wild-type mice, with reduced activation in knockout mice.; Absence of RAMP1/3 impaired cagrilintide's weight loss efficacy but improved salmon calcitonin's effect.
Liraglutide 3.0 mg daily induces 6-8% weight loss; semaglutide 2.4 mg weekly achieves 12-15%.; Tirzepatide, a dual GIP/GLP-1 agonist, induces about 20% weight loss in obese people without diabetes.; Combination semaglutide/cagrilintide and oral semaglutide are in phase III development.; Adverse events are gastrointestinal (nausea, vomiting, obstipation, diarrhea) and mitigated by slow up titration.
Cagrisema led to 9.07% greater weight loss and 9.11 kg greater absolute loss vs semaglutide at 20-32 weeks.; Cagrilintide 2.4 mg had similar weight loss to semaglutide/liraglutide at 26-32 weeks.; Gastrointestinal adverse events and vomiting were significantly higher with Cagrisema vs semaglutide.; Vomiting was significantly lower with cagrilintide alone vs semaglutide/liraglutide.
Frequently asked questions
What is Cagrilintide?
Cagrilintide (AM833, NNC0174-0833) is a long-acting acylated amylin analog designed to mimic the physiological effects of amylin, a pancreatic hormone that regulates satiety and gastric emptying. Its mechanism of action involves binding to amylin receptors in the area postrema and other central nervous system regions,
How does Cagrilintide work?
Long-acting amylin analog in trials for obesity, including combination with semaglutide (CagriSema).
What is the research status of Cagrilintide?
Cagrilintide is currently classified as clinical trials, with 103 research references on record. This is for research purposes only and is not medical advice.
What is the molecular weight of Cagrilintide?
Cagrilintide has a molecular weight of approximately 4409 g/mol (formula C194H312N54O59S2).
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