Cagrilintide vs Pramlintide

Cagrilintide and pramlintide are synthetic analogues of the 37-residue hormone amylin, and one is built from the other: pramlintide was the backbone peptide used to make cagrilintide (Cao et al., 2025). Pramlintide is human amylin with prolines at positions 25, 28 and 29 (da Silva et al., 2016). Cagrilintide keeps those prolines, adds three more substitutions (N14E, V17R and Y37P) and carries a C20 diacid on a gamma-glutamic acid linker at its N-terminus (Cao et al., 2025).

Cagrilintide · 10mg

$79.99

Buy 3, get 1 FREE

Add to Cart

View product

The extra changes alter how the peptide behaves at the receptor. In a 2021 comparison across 25 pharmacological endpoints, pramlintide acted as an amylin-receptor-selective agonist, while cagrilintide (tested as AM833) was a nonselective agonist of the amylin and calcitonin receptors with a profile unlike any of the other peptides tested (Fletcher et al., 2021). This page compares the two molecules on identity, receptor pharmacology and solution chemistry, and maps each to the lab questions it suits.

This article is a scientific overview for laboratory researchers. The research-grade cagrilintide supplied by Prime Peptide Solutions is sold strictly for in-vitro laboratory research. It is not approved for human use and is not for human or animal consumption. Pramlintide is not sold here.

About Cagrilintide

Design. Cagrilintide came out of structure-activity work on a stable, lipidated amylin analogue; the challenge was amylin's high propensity to form amyloid fibrils (Kruse et al., 2021). On the pramlintide backbone, the N14E and V17R pair was added to counteract fibril formation, predicted to stabilize the N-terminal alpha-helix (residues 5-18) through an intramolecular salt bridge. Pro37 replaces the C-terminal tyrosine; in rat amylin that swap was well tolerated and raised affinity and activity at both the calcitonin receptor and the amylin receptors, in some cases with reduced selectivity between them (Cao et al., 2025).

Receptor pharmacology. Across binding, activation and receptor-regulation endpoints, cagrilintide had a profile unlike pramlintide, salmon calcitonin, rat amylin, human calcitonin or two lipidated research analogues (Fletcher et al., 2021). In receptor-specific assays it activated both amylin and calcitonin receptors, while the salmon-calcitonin-based dual agonist KBP-336 was more potent and biased toward the calcitonin receptor (Larsen et al., 2022). Functional assays showed non-selective Gs activation through the calcitonin receptor and AMY1 (Gu et al., 2026).

Structure. Cryo-EM structures with Gs-coupled AMY1, AMY2, AMY3 and calcitonin receptors show an amylin-like binding mode with distinct receptor dynamics (Cao et al., 2025). A second set of structures highlights Phe23 at the transmembrane bundle, the Glu14-Arg17 salt bridge and Pro37 contacting the receptor extracellular domain (Gu et al., 2026).

Analytics and tools. In-vitro metabolism models broke cagrilintide down from both termini, and validated LC-MS/MS methods cover the peptide and its products (Alhalabi et al., 2026). For rodent mode-of-action work, a tool analogue, 0839, shares 95% sequence homology and an identical acylation side chain (Gabery et al., 2025). Cagrilintide has been evaluated in phase 1 and phase 2 clinical trials (Cao et al., 2025); the clinical literature is outside the scope of this page.

About Pramlintide

Where the prolines come from. Synthetic-peptide work traced human amylin's fibril formation to positions 20-29, found Ala-Ile-Leu-Ser-Ser (25-29) strongly amyloidogenic, and showed that a proline-for-serine substitution at 28, as in several rodents, almost completely inhibits fibril formation (Westermark et al., 1990). Rat amylin carries prolines at 25, 28 and 29 (UniProt P12969), the same three positions substituted in pramlintide, a triple-proline analogue designed to address the solubility and amyloid characteristics of human amylin (da Silva et al., 2016).

Solution behaviour. The prolines did not make pramlintide fibril-proof. Ion mobility mass spectrometry showed it can assemble into multimers, and it formed amyloid fibrils in vitro in a pH-dependent process within a few hours (da Silva et al., 2016). An empirical-phase-diagram study found little defined structure in dilute solution, stability in its pH 4 formulation, and a tendency to aggregate at high concentration at pH 6 to 7.5 (Nonoyama et al., 2008). Zn(II) binds its Lys1 amine and His18 imidazole and bends the peptide; the initially soluble complex formed fibrillar, oligomeric aggregates after a lag of about 20 hours (Łoboda and Rowińska-Żyrek, 2017; Dudek et al., 2022).

Degradation chemistry. In a pH 4.0 pramlintide formulation stressed at 40 °C for 45 days, deamidation accounted for about 64% of thermal degradation, cyclic imides about 20% and backbone hydrolysis the rest, with six of eight possible deamidation sites affected (Hekman et al., 1999). Hydrolysis cut the chain at His18-Ser19 and Ser19-Ser20 (Hekman et al., 1998). A forced-degradation study found extensive degradation under hydrolytic, oxidative and thermal stress, minimal degradation under light, and separated the products by reversed-phase and strong-cation-exchange HPLC for LC-MS identification (Yuan et al., 2018).

Receptor pharmacology. In the 2021 seven-agonist comparison, pramlintide was the amylin-receptor-selective reference (Fletcher et al., 2021). A 2016 review notes that little was known about amylin's structure-function relationships, largely because of the native peptide's aggregation and solubility properties, and describes how that knowledge is aiding the design of more potent and stable amylin mimetics (Bower and Hay, 2016).

Which Fits the Research Question?

The two peptides share a backbone, so the choice turns on the four places where they differ and on what each literature covers.

• Amylin-receptor-selective activation: pramlintide is the selective reference in the 2021 comparison. Cagrilintide also activates the calcitonin receptor, so in a cell line that expresses the calcitonin receptor without a RAMP, the two are expected to read out differently.
• Combined amylin and calcitonin receptor activation: cagrilintide, with KBP-336 or salmon calcitonin as calcitonin-backbone comparators.
• Structural biology with a lipidated ligand: cagrilintide, which has published cryo-EM structures at all four of its targets.
• Aggregation and metal-binding chemistry: pramlintide has the larger published record: fibril kinetics, phase behaviour and zinc complexes.
• Degradation and analytical methods: pramlintide's heat-stress products are mapped residue by residue; for cagrilintide, published work covers in-vitro metabolism and LC-MS/MS detection.
• The effect of lipidation alone: neither pair member isolates it, because the peptides also differ at three residues. A matched non-lipidated control is needed.

Only cagrilintide is stocked here, as Cagrilintide (10mg vial). For cagrilintide beside a peptide from a different receptor family, see retatrutide vs cagrilintide. Handling guides: peptide storage and HPLC and mass spectrometry.