Cagrilintide vs Retatrutide: An Amylin Analog and a Triple Agonist Compared
Cagrilintide and Retatrutide are both long-acting, lipidated peptides of similar size, and both come up in metabolic research. They act on entirely different receptor families. Cagrilintide is an amylin analog that targets amylin and calcitonin receptors; Retatrutide is a single peptide built to activate the GIP, GLP-1 and glucagon receptors. This post compares their design, receptor pharmacology and lab characterization.
Research blog: general laboratory-science and literature context. Not medical advice. Sealed Peptides materials are for laboratory research use only, and are not for human or veterinary use.
Two different hormone families
Cagrilintide is built on amylin, a 37-residue peptide hormone co-secreted with insulin by pancreatic beta cells [1]. Native amylin is known for a strong tendency to form amyloid fibrils, which made it hard to develop; cagrilintide was designed as a stable, lipidated, long-acting analog to get around that [2].
Retatrutide (LY3437943) belongs to the incretin and glucagon family. It is one peptide designed to activate three receptors: the glucagon receptor (GCGR), the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R). In vitro it shows balanced GCGR and GLP-1R activity and stronger GIPR activity [3].
Structure at a glance
- Cagrilintide: modified amylin sequence with the conserved Cys2-Cys7 disulfide ring and a fatty-acid side chain for albumin binding; formula C194H312N54O59S2, listed molecular weight 4409 Da.
- Retatrutide: 39-residue peptide with non-coded residues such as Aib and a fatty diacid chain on a lysine side chain; formula C221H342N46O68, listed molecular weight 4731.3 Da.
- Telling them apart on paper: the two sulfur atoms in cagrilintide's formula come from its disulfide bridge. Retatrutide has no cysteine or methionine, so its formula has no sulfur at all.
Receptor pharmacology
Amylin receptors are not single proteins. They form when the calcitonin receptor pairs with one of three receptor activity-modifying proteins (RAMP1 to RAMP3), giving the AMY1, AMY2 and AMY3 subtypes [4]. Amylin analogs are therefore compared on both amylin receptor and calcitonin receptor activity, and structure-function reviews discuss how individual residues shift that balance [5].
Retatrutide works on class B GPCRs of a different family. Its glucagon-receptor component is the main thing that separates it from dual GIP/GLP-1 agonists such as Tirzepatide; reviews of glucagon agonism describe how that receptor is studied in energy-expenditure and liver-metabolism models [6]. Tirzepatide vs Retatrutide covers that comparison in detail.
Clinical development vs research material
Both molecules come from pharmaceutical programs and have been evaluated in clinical trials by their developers [7] [8]. Those regulated programs are separate from research-grade material. Nothing on this page concerns use in people; the Cagrilintide and Retatrutide research overviews summarize the published literature with citations.
Checking each one in the lab
At 4.4 to 4.7 kDa, both appear in electrospray mass spectra as a series of multiply charged ions, so the mass is reconstructed from several charge states. The roughly 322 Da difference between their listed masses makes them easy to tell apart.
Cagrilintide has an extra check: its intact disulfide. Reduction breaks the ring and adds about 2 Da; the disulfide and free thiol guide explains how that is tested. Both are lipidated, amphiphilic peptides, and amylin-derived sequences in particular have a history of fibril formation, so Aggregation and Solubility deserve attention; see the solubility and aggregation guide.
Handling notes
Both are supplied as Lyophilized powders and stored sealed and frozen. For solution arithmetic with each listed molecular weight, see the Cagrilintide and Retatrutide calculators, and the Retatrutide vial size post covers how vial mass changes the arithmetic.
Terms used in this guide
Related tools and guides
References
- Hay DL, Chen S, Lutz TA, Parkes DG, Roth JD. Amylin: Pharmacology, Physiology, and Clinical Potential. Pharmacol Rev. 2015;67(3):564-600. PMID 26071095 · DOI
- Kruse T, Hansen JL, Dahl K, Schäffer L, Sensfuss U, Poulsen C, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. J Med Chem. 2021;64(15):11183-11194. PMID 34288673 · DOI
- Coskun T, Urva S, Roell WC, Qu H, Loghin C, Moyers JS, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. 2022;34(9):1234-1247.e9. PMID 35985340 · DOI
- Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, et al. International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev. 2002;54(2):233-46. PMID 12037140 · DOI
- Bower RL, Hay DL. Amylin structure-function relationships and receptor pharmacology: implications for amylin mimetic drug development. Br J Pharmacol. 2016;173(12):1883-98. PMID 27061187 · DOI
- Winther JB, Holst JJ. Glucagon agonism in the treatment of metabolic diseases including type 2 diabetes mellitus and obesity. Diabetes Obes Metab. 2024;26(9):3501-3512. PMID 38853300 · DOI
- Lau DCW, Erichsen L, Francisco AM, Satylganova A, le Roux CW, McGowan B, et al. 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. Lancet. 2021;398(10317):2160-2172. PMID 34798060 · DOI
- Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. PMID 37366315 · DOI
Cited literature is provided for scientific context only. Many of these reviews concern proteins or pharmaceutical development; they are cited for general chemistry and do not describe or endorse any use of these products.
For laboratory research use only. Not for human or veterinary use. This post is general chemistry and literature context and does not describe or endorse any use of Sealed Peptides products.
