Cagrilintide
Cagrilintide (NN9838 / AM833)
Investigational once-weekly long-acting amylin analog. Engineered for SC weekly dosing through C20 fatty diacid acylation (vs pramlintide's tid dosing requirement). Solo development paused. Novo's commercial path is via the CagriSema fixed-dose combination with semaglutide. Solo cagrilintide demonstrated -10.8% weight loss at 4.5mg in phase 2 (similar to liraglutide 3.0mg).
At a glance
- Half-life
- ~7 days 159-195h across 0.16-4.5mg doses (median ~7-8 days). C20 eicosanedioic fatty diacid + gamma-glutamic acid linker enables albumin binding. Tmax 24-72h post SC injection.
- Tmax
- ~48 h
- Routes
- SubQ
- Evidence base
- 3 studies 2 human · 1 review
Mechanism
Dual amylin receptor (AMY1R, AMY2R, AMY3R = calcitonin receptor + RAMP1-3) and calcitonin receptor agonist. Mimics native amylin (co-secreted with insulin from pancreatic beta-cells in 1:100 ratio). Effects: slows gastric emptying (independent of GLP-1 mechanism), suppresses postprandial glucagon, activates hindbrain area postrema neurons for satiety, increases meal-related satiety signaling. Phase 2 (n=706): -6.0 to -10.8% weight loss at 0.3-4.5 mg vs -3.0% placebo. C20 fatty diacid + gamma-Glu linker enables albumin binding for once-weekly dosing (t½ 159-195h). Synergy with GLP-1: combined cagrilintide + semaglutide 2.4 mg achieved -17.1% weight loss vs -9.8% semaglutide alone: complementary appetite/satiety pathways with no receptor overlap, basis for CagriSema combination.
Dosing
Any amounts shown here are reported from published studies only. 2 of 3 catalogued studies involved human subjects. COMPOUND does not publish its own dosing guidance.
Where a study reports an amount, it appears in that study's entry below, attributed to the source.
Published evidence
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Human RCT 2021
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
Phase 2, n=706, 26 weeks: weight loss 6.0-10.8% across 0.3-4.5mg doses vs 3.0% placebo. Cagrilintide 4.5mg superior to liraglutide 3.0mg (-10.8% vs -9.0%, p=0.03).
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Human RCT 2021
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
Phase 1b, 20 weeks (n=96): cagrilintide 2.4 mg + semaglutide 2.4 mg achieved -17.1% weight loss vs -9.8% with semaglutide 2.4 mg alone. Established proof-of-concept for the fixed-ratio combination.
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Review 2021
Development of Cagrilintide, a Long-Acting Amylin Analogue
Medicinal chemistry: C20 fatty diacid + gamma-Glu linker yields t½ 159-195h. Foundational PK paper.
Reported side effects
- Nausea
- Common Mild · Phase 2 solo: 20-47% across doses vs 18% placebo.
- Constipation
- Common Mild · Phase 2: more common than with GLP-1 alone.
- Diarrhea
- Occasional Mild · Less common than with GLP-1 RAs.
- Injection site reactions
- Common Mild · Erythema, pruritus, induration.
- Decreased appetite
- Common Mild · Wanted effect; satiety enhancement.
- Hypoglycemia
- Rare Mild · Amylin enhances insulin satiety signaling but is not insulinotropic per se. Hypo risk much lower than GLP-1 RAs.
Interactions
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Insulin Synergy
Amylin combined with insulin can theoretically increase hypoglycemia risk; pramlintide label requires 50% insulin dose reduction.
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Oral medications (general) Absorption interference
Amylin slows gastric emptying independent of GLP-1 mechanism. May reduce absorption rate of oral drugs.
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Semaglutide (SC) Synergy
Complementary appetite/satiety pathways: basis for CagriSema. Synergistic weight loss when combined.
Reconstitution and storage
N/A pre-approval. Likely SC pen if launched standalone.
N/A pre-approval.