Cagrilintide (NN9838 / Long-Acting Amylin Analog)
Also Known AsNN9838 · AM833 · CagriSema component · Long-acting amylin analog
Cagrilintide was developed by Novo Nordisk as a long-acting acylated analog of human amylin (islet amyloid polypeptide, IAPP). Native amylin is a 37-amino-acid peptide co-secreted with insulin from pancreatic beta cells but has a half-life of only ~15 minutes and aggregation tendency. Cagrilintide incorporates amino acid substitutions and a C-18 fatty diacid side chain (similar to semaglutide's albumin-binding moiety) to achieve once-weekly dosing and prevent amyloid aggregation.
How Cagrilintide Works
Amylin Receptor Agonism (CTR/RAMP Complex)
Cagrilintide activates amylin receptors (AMY1, AMY2, AMY3), which are heterodimers of the calcitonin receptor (CTR) with receptor activity-modifying proteins (RAMP1, RAMP2, or RAMP3). Receptor activation increases intracellular cAMP and activates downstream signaling via PKA and ERK1/2 in the area postrema and hypothalamus, suppressing appetite and slowing gastric emptying.
Hypothalamic Appetite Regulation
Amylin signaling in the area postrema and nucleus tractus solitarius (NTS) suppresses food intake through both direct satiation (meal termination) and sustained anorexia (inter-meal appetite reduction). These brainstem signals are relayed to the lateral parabrachial nucleus and hypothalamic feeding centers, reducing orexigenic (NPY/AgRP) and enhancing anorexigenic (POMC/CART) signaling.
Gastric Emptying Modulation
Amylin receptor activation slows gastric emptying rate, complementing its central appetite-suppressing effects. This delays nutrient delivery to the small intestine, reduces postprandial glucose excursions, and enhances early satiation during meals. The mechanism involves vagal afferent signaling from the gastric antrum.
Published Research
Obesity & Weight Management
StrongPhase II trials of cagrilintide monotherapy demonstrated dose-dependent weight loss of up to 10.8% over 26 weeks in adults with overweight/obesity, exceeding the weight loss typically seen with GLP-1 agonists alone at comparable timepoints. Cagrilintide accesses the amylin pathway — distinct from GLP-1 — activating complementary appetite-suppressing brainstem circuits.
Combination Therapy with Semaglutide (CagriSema)
StrongCagriSema (cagrilintide + semaglutide co-formulation) targets both amylin and GLP-1 pathways simultaneously. Phase II data showed CagriSema achieved 15.6% weight loss at 32 weeks vs. 5.1% for cagrilintide alone and 8.2% for semaglutide alone, demonstrating synergistic rather than merely additive efficacy. Phase III trials (REDEFINE program) are ongoing.
Type 2 Diabetes
ModerateAmylin receptor agonism improves glycemic control through multiple mechanisms: delayed gastric emptying (reduced postprandial glucose), appetite suppression (weight loss improving insulin sensitivity), and direct glucagon suppression. Cagrilintide, particularly in combination with semaglutide, is being investigated for glycemic endpoints in the Phase III REDEFINE program.
Complementary Pathway Pharmacology
ModerateThe amylin and GLP-1 pathways represent distinct but complementary appetite-regulatory circuits. Amylin acts primarily through the area postrema (outside the blood-brain barrier), while GLP-1 engages hypothalamic and mesolimbic reward centers. Co-targeting both produces weight loss that neither achieves alone, establishing a precedent for multi-pathway obesity pharmacotherapy.
Safety Profile
Phase II clinical trial data for cagrilintide shows a safety profile consistent with the amylin receptor agonist class. Gastrointestinal adverse events (nausea, vomiting, diarrhea, constipation) are the most common, occurring more frequently at higher doses and typically diminishing over time. Injection site reactions are reported. No pancreatitis signal has been detected. When combined with semaglutide (CagriSema), GI adverse event rates are comparable to semaglutide monotherapy, suggesting the combination does not amplify tolerability concerns.
Handling & Storage
Reconstitute with bacteriostatic water. Cagrilintide is an acylated peptide with good aqueous stability due to its albumin-binding fatty acid chain. Store reconstituted solution at 2-8°C and use within 21 days. Lyophilized powder stable at -20°C for 24+ months. Do not freeze reconstituted solution.
Peer-Reviewed Literature
- 1
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
Lau DCW, Erichsen L, Francisco-Ziller N, et al.
- 2
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
Enebo LB, Berthelsen KK, Kankam M, et al.
- 3
Control of food intake and energy expenditure by amylin — therapeutic implications
Lutz TA.
- 4
Amylin: pharmacology, physiology, and clinical potential
Hay DL, Chen S, Lutz TA, et al.
Cagrilintide FAQ
What is Cagrilintide?
Cagrilintide is a long-acting acylated analog of human amylin, developed by Novo Nordisk. It activates amylin receptors (heterodimers of the calcitonin receptor with RAMPs) in the brainstem to suppress appetite, slow gastric emptying, and reduce food intake. Its C-18 fatty diacid chain enables once-weekly dosing through albumin binding, similar to the technology used in semaglutide.
What is CagriSema?
CagriSema is a co-formulated combination of cagrilintide (amylin analog) and semaglutide (GLP-1 analog) in a single injection. Phase II data showed CagriSema achieves ~15.6% weight loss — nearly double semaglutide alone. The rationale is that amylin and GLP-1 activate complementary appetite-regulatory circuits in the brain, producing synergistic rather than additive efficacy.
How does amylin signaling differ from GLP-1?
Amylin acts primarily through the area postrema (a circumventricular organ outside the blood-brain barrier) and nucleus tractus solitarius, controlling meal termination and satiation. GLP-1 engages hypothalamic appetite centers and mesolimbic reward circuits, affecting food reward and craving. These are anatomically and pharmacologically distinct pathways, which is why combining them produces enhanced weight loss.
How should Cagrilintide be stored?
Lyophilized Cagrilintide should be stored at -20°C for long-term stability. Once reconstituted with bacteriostatic water, store at 2-8°C and use within 21 days. The acylated fatty acid chain provides good stability in solution. Do not freeze reconstituted material.
Cagrilintide Products
All compounds 99%+ purity, verified by Janoshik Analytical. GMP-manufactured lyophilized powder.
Cagrilintide
5mgThe semaglutide amplifier — a long-acting amylin that pairs with GLP-1 drugs to supercharge weight loss. Part of the CagriSema combination that's the next breakthrough.
- Long-acting amylin analog for appetite suppression
- Pairs with semaglutide for enhanced weight loss (CagriSema)
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10mg/10mgThe nuclear option for weight loss — three of the most powerful metabolic compounds combined into one protocol. Hits every appetite and fat-burning pathway known to science.
- Triple-compound weight loss protocol in one preparation
- Combines semaglutide + cagrilintide + retatrutide mechanisms
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Disclaimer: This monograph is provided for educational and research purposes only. G26x Peptides products are sold exclusively as research chemicals. They are not intended for human consumption, therapeutic use, or as dietary supplements. All research should be conducted in compliance with applicable laws and institutional review board protocols. Information presented here is sourced from published peer-reviewed literature and does not constitute medical advice.