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
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-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.
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.
All 15 GLP-1RAs effectively lowered HbA1c and fasting plasma glucose versus placebo.; Tirzepatide showed the largest HbA1c reduction (-2.10%) and fasting glucose reduction (-3.12 mmol/L).; CagriSema (semaglutide with cagrilintide) produced the highest weight loss (-14.03 kg), followed by tirzepatide (-8.47 kg).; Semaglutide significantly lowered LDL cholesterol (-0.16 mmol/L) and total cholesterol (-0.48 mmol/L).
Cagrilintide is an amylin analog that induces satiety via homeostatic and hedonic brain regions.; Semaglutide reduces appetite through hypothalamic GLP-1 receptors and delays gastric emptying.; Combination therapy targets multiple obesity pathways, showing additive appetite reduction.; Clinical trials demonstrate significant weight loss with cagrilintide alone and with semaglutide.
CagriSema reduced HbA1c by 2.2 percentage points vs 1.8 for semaglutide (p=0.075) and 0.9 for cagrilintide (p<0.0001).; CagriSema led to 15.6% body weight loss vs 5.1% for semaglutide and 8.1% for cagrilintide (both p<0.0001).; Time in range (3.9-10.0 mmol/L) improved from 45.9% to 88.9% with CagriSema.; Gastrointestinal adverse events were most common; no severe hypoglycemia or fatal events occurred.
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 90 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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