Cagrilintide

Also known as: AM833, NN9838, NN0174-0833

Evidence: Clinical

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Overview

Long-acting lipidated amylin analog that activates amylin and calcitonin receptors; once-weekly 0.3 to 4.5 mg cut body weight 6.0 to 10.8% at 26 weeks in a phase 2 trial (n=706).

Cagrilintide (AM833, NN9838) is a lipidated, long-acting analog of the pancreatic hormone amylin, designed by Novo Nordisk for once-weekly subcutaneous dosing (Kruse 2021). As monotherapy, a 26-week phase 2 trial in 706 adults with overweight or obesity found weight reductions of 6.0 to 10.8% across 0.3 to 4.5 mg weekly, against 3.0% with placebo and 9.0% with liraglutide 3.0 mg (Lau 2021). Most clinical work pairs it with semaglutide 2.4 mg as CagriSema. Phase 3 trials report a 20.4% mean weight reduction at 68 weeks in adults without diabetes (REDEFINE 1) and 13.7% in adults with type 2 diabetes (REDEFINE 2). No cagrilintide product, alone or combined, has an approval listed in Drugs@FDA as of October 2026.

Benefits

Weight loss as monotherapy (human phase 2 RCT), larger weight loss combined with semaglutide (human phase 3 RCT), lower HbA1c with semaglutide in type 2 diabetes (human phase 2 RCT), reduced food intake (mouse)

Dosing reference

Research dose: 2.4 mg once weekly in phase 3 (alone and with semaglutide 2.4 mg); phase 2 dose-finding tested 0.3 to 4.5 mg once weekly
Range: 300 to 4500 mcg, 1x weekly
Reconstitution: 2 mL bacteriostatic water
Common vial sizes: 5 mg, 10 mg

Subcutaneous, once weekly. Phase 2 escalated to the target dose over up to 6 weeks and treated for 26 weeks (Lau 2021). The phase 1b combination study co-escalated cagrilintide and semaglutide every 4 weeks over 16 weeks (Enebo 2021). Phase 3 used 2.4 mg for 68 weeks, alone or with semaglutide 2.4 mg (Garvey 2025). Investigational; not approved.

Mechanism

Cagrilintide is a nonselective agonist of amylin receptors (the calcitonin receptor paired with RAMP1, 2 or 3) and of the calcitonin receptor itself. Across 25 in vitro endpoints its profile differed from both pramlintide and salmon calcitonin (Fletcher 2021). A C20 fatty diacid attached through a gamma-glutamic acid spacer binds albumin and extends the half-life to about a week (Kruse 2021; Enebo 2021). In diet-induced obese mice, weight loss depended on amylin receptors 1 and 3, and treatment activated neurons in the dorsal vagal complex and lateral parabrachial nucleus (Carvas 2025). Brainstem amylin signalling is the proposed route to reduced food intake in humans.

Evidence

Clinical: at least one published human trial or an approved drug

Phase 1b with semaglutide 2.4 mg, 20 weeks (n=96): cagrilintide 1.2 and 2.4 mg gave 15.7% and 17.1% weight loss vs 9.8% with semaglutide plus placebo; half-life 159 to 195 h (Enebo et al., 2021)
Phase 2 monotherapy, 26 weeks (n=706): 0.3 to 4.5 mg weekly reduced body weight 6.0 to 10.8% vs 3.0% with placebo; 4.5 mg exceeded liraglutide 3.0 mg (9.0%) (Lau et al., 2021)
Phase 2 in type 2 diabetes, 32 weeks (n=92): weight change -8.1% with cagrilintide alone and -15.6% with CagriSema; HbA1c -0.9 and -2.2 points (Frias et al., 2023)
Phase 3 REDEFINE 1, 68 weeks (n=3417, no diabetes): CagriSema 2.4/2.4 mg gave -20.4% vs -3.0% with placebo; gastrointestinal events 79.6% vs 39.9% (Garvey et al., 2025)
Phase 3 REDEFINE 2, 68 weeks (n=1206, type 2 diabetes): CagriSema -13.7% vs -3.4% with placebo (Davies et al., 2025)
Human-trial status: phase 3 as a fixed combination with semaglutide (REDEFINE, REIMAGINE programs); no cagrilintide product approved by the FDA in Drugs@FDA as of October 2026

References

Side effects

In the phase 2 monotherapy trial, gastrointestinal events (nausea, constipation, diarrhoea) affected 41 to 63% vs 32% on placebo, nausea alone 20 to 47% vs 18%, and administration-site reactions were common; 4% stopped for adverse events (Lau 2021). With semaglutide 2.4 mg, gastrointestinal events affected 79.6% vs 39.9% on placebo over 68 weeks, mostly transient and mild to moderate (Garvey 2025). Safety of cagrilintide alone beyond 68 weeks is not published.

Storage

Storage: Refrigerated (2-8°C); general lyophilised-peptide guidance, no compound-specific CoA located
Lyophilized: 24+ months refrigerated
Reconstituted: 28 days refrigerated

Pharmacology

Half-life: 159 to 195 h (adults with overweight or obesity, subcutaneous, given with semaglutide 2.4 mg); median tmax 24 to 72 h
Bioavailability: No absolute bioavailability published; subcutaneous exposure rose in proportion to dose from 0.16 to 4.5 mg (human, Enebo 2021)
Molecular weight: 4409.1 Da
Sequence: [C20 diacid-gamma-Glu]-KCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP-NH2 (Cys2-Cys7 disulfide)

Stacks with

Semaglutide