Retatrutide vs Tirzepatide vs Cagrilintide: How the Receptor Profiles Compare.

Retatrutide, tirzepatide and cagrilintide are three research peptides that differ at the receptor level. Retatrutide (LY3437943) is a single peptide with agonist activity at the GIP, GLP-1 and glucagon receptors. Tirzepatide (LY3298176) is a dual GIP and GLP-1 receptor agonist. Cagrilintide (NNC0174-0833) is a long-acting amylin analog acting at the amylin and calcitonin receptors, a different receptor family entirely. Semaglutide, a single GLP-1 receptor agonist, is the reference point the field measures against. This article compares the three compounds on receptor pharmacology and the published trial record only. It does not discuss trial results, and every material referenced is sold for in vitro research use only.

What is retatrutide, and is GLP-3 RT retatrutide?

Retatrutide is the international nonproprietary name for LY3437943, a synthetic peptide developed by Eli Lilly that acts as an agonist at three receptors: the gastric inhibitory polypeptide receptor (GIPR, also written GIP receptor), the glucagon-like peptide 1 receptor (GLP-1R) and the glucagon receptor (GCGR). The discovery paper in Cell Metabolism describes it as a single peptide engineered to carry all three activities, with in vitro assays showing balanced GCGR and GLP-1R activity and comparatively greater GIPR activity (Coskun et al., 2022). Its pharmacokinetic profile was designed for once-weekly administration in trials. Because it targets three receptors rather than one or two, the literature calls it a triple agonist or triagonist. GLP-3 RT is the Next Level Labs catalog name for its retatrutide research vial, so yes, GLP-3 RT is retatrutide. The name is a catalog code, not a pharmacological class. The research-store vial is a synthetic peptide sold for laboratory use and is not the investigational pharmaceutical product.

What is tirzepatide?

Tirzepatide is LY3298176, also developed by Eli Lilly. It is a single peptide with agonist activity at two receptors, GIPR and GLP-1R, which is why the SURMOUNT-1 publication describes it as a GIP and GLP-1 receptor agonist (Jastreboff et al., 2022). Compared with semaglutide, which engages GLP-1R only, tirzepatide adds the GIP receptor. Compared with retatrutide, it lacks the glucagon receptor activity. That single receptor difference is the whole distinction between "dual" and "triple" in the naming. Tirzepatide is an FDA-approved prescription pharmaceutical; the tirzepatide research vial sold by Next Level Labs is a synthetic peptide for in vitro research and is not that product.

What is cagrilintide, and how is it different from a GLP-1 agonist?

Cagrilintide is NNC0174-0833, a long-acting amylin analog developed by Novo Nordisk (Lau et al., 2021; ClinicalTrials.gov NCT03856047). Amylin is a pancreatic peptide hormone in the calcitonin family, not the incretin family, so cagrilintide does not bind GLP-1R, GIPR or GCGR. Its receptors are the amylin receptors, which are formed when the calcitonin receptor (CTR) pairs with one of three receptor activity-modifying proteins (RAMP1, RAMP2 or RAMP3), giving the AMY1, AMY2 and AMY3 receptors (Hay et al., 2018). Preclinical receptor assays classify cagrilintide as a dual amylin and calcitonin receptor agonist, meaning it activates both the CTR/RAMP complexes and the calcitonin receptor on its own (Larsen et al., 2022). This is why "cagrilintide vs semaglutide" or "cagrilintide vs tirzepatide" is not a like-for-like comparison: the compounds engage separate receptor systems, which is also the rationale for studying cagrilintide co-administered with semaglutide as CagriSema. The cagrilintide research vial at Next Level Labs is a synthetic peptide for laboratory use.

How do the receptor profiles differ at the signaling level?

All of the receptors involved are class B G protein-coupled receptors, but they split into two families. GLP-1R, GIPR and GCGR belong to the secretin-like family: each is a stand-alone receptor that couples predominantly to Gs and raises intracellular cyclic AMP on agonist binding. Semaglutide engages one of them, tirzepatide two, and retatrutide all three. The amylin receptors belong to the calcitonin receptor family and are structurally different. The calcitonin receptor alone binds calcitonin; only when it heterodimerizes with a RAMP does the complex become an amylin receptor with amylin-preferring pharmacology, and the RAMP subtype determines which of AMY1, AMY2 or AMY3 is formed (Hay et al., 2018). Cagrilintide acts on those complexes and on the bare calcitonin receptor.

Three points follow from this. First, receptor count is not the same as receptor family: retatrutide's three targets sit in one family, while cagrilintide's targets sit in a second. Second, "balance" between receptors is a measured property, not a label. Coskun and colleagues reported retatrutide's relative activity at GCGR, GIPR and GLP-1R from in vitro assays, and Larsen and colleagues compared cagrilintide's CTR-versus-amylin-receptor balance against a calcitonin-derived analog. Third, because the incretin and amylin systems do not overlap, a GLP-1 receptor agonist and an amylin analog can be studied side by side without competing for the same binding site, which is the mechanistic premise of the CagriSema program.

What has been published on each compound?

Retatrutide has a preclinical and clinical proof-of-concept paper in Cell Metabolism (Coskun et al., 2022), a phase 1b trial in The Lancet designed to characterize pharmacokinetics and pharmacodynamics across ascending once-weekly administration levels over 12 weeks (Urva et al., 2022), and a phase 2 trial in the New England Journal of Medicine (Jastreboff et al., 2023; NCT04881760) designed to characterize the response to once-weekly administration against placebo over 48 weeks, with a prespecified anthropometric endpoint. Tirzepatide has completed phase 3; SURMOUNT-1 in the New England Journal of Medicine (Jastreboff et al., 2022; NCT04184622) was a 72-week placebo-controlled trial with a prespecified anthropometric endpoint. Cagrilintide has a phase 2 trial in The Lancet at 57 sites in ten countries, designed to characterize the response across multiple once-weekly administration levels against placebo and an active comparator (Lau et al., 2021; NCT03856047). The CagriSema combination reached phase 3 with REDEFINE 1 in the New England Journal of Medicine (Garvey et al., 2025). This article states only that these trials exist, their phase and what they were designed to measure; it does not report their results.

None of these compounds is approved for sale by a research store as a drug. Tirzepatide is an approved pharmaceutical, and retatrutide and cagrilintide are investigational, but in every case the research-store compound is a synthetic peptide for in vitro use and is not the pharmaceutical product.

How do retatrutide, tirzepatide and cagrilintide compare side by side?

Dimension	Retatrutide (GLP-3 RT)	Tirzepatide	Cagrilintide
Receptor targets	GIPR, GLP-1R and GCGR (triple agonist)	GIPR and GLP-1R (dual agonist)	Amylin receptors (CTR plus RAMP1, 2 or 3) and the calcitonin receptor
Peptide class	Single-peptide incretin and glucagon receptor triagonist	Single-peptide incretin dual agonist	Long-acting amylin analog
Code name and developer	LY3437943, Eli Lilly	LY3298176, Eli Lilly	NNC0174-0833, Novo Nordisk
Half-life class as published	Designed for once-weekly administration in trials	Designed for once-weekly administration in trials	Long-acting; designed for once-weekly administration in trials
Development status	Phase 2 published (NEJM 2023); phase 3 program registered	Phase 3 published (NEJM 2022); FDA-approved pharmaceutical	Phase 2 published alone (Lancet 2021); phase 3 published as CagriSema (NEJM 2025)
NLL product page	/products/glp-3-rt	/products/tirzepatide	/products/cagrilintide
What the NLL certificate reports	Identity by LC-MS, purity by HPLC	Identity by LC-MS, purity by HPLC	Identity by LC-MS, purity by HPLC

What does the certificate of analysis show?

Each Next Level Labs vial carries a lot number that maps to its own third-party certificate, published on the Lab Reports page before the compound is listed. The certificate reports two things relevant to this comparison: identity, confirmed by LC-MS mass spectrometry so the peptide in the vial matches the sequence on the label, and purity, measured by HPLC. According to the published COA ledger, the current retatrutide lot PS07-R310 was tested by ILS Laboratories at 99.52% purity, with the certificate dated August 11, 2026, and a second retatrutide lot, PS07-R320, tested at 99.20% by the same laboratory on the same date. The tirzepatide lot PS07-T210 was tested by ILS Laboratories at 99.72% purity, certificate dated August 11, 2026. Cagrilintide's report is published on /lab-reports without a figure in the ledger, so read the certificate itself rather than a summary. A certificate establishes what is in the vial; it says nothing about how a compound behaves at a receptor, which is why the two halves of this article are kept separate. For a walkthrough of the document itself, see how to read a peptide COA, and browse the full GLP-axis category on the GLP-axis research page.

Frequently asked questions

Is GLP-3 RT the same thing as retatrutide?

Yes. GLP-3 RT is the Next Level Labs catalog name for its retatrutide research vial. Retatrutide is the international nonproprietary name for LY3437943, the single-peptide agonist of the GIP, GLP-1 and glucagon receptors developed by Eli Lilly. The vial's lot number maps to a published certificate reporting identity by LC-MS and purity by HPLC. It is not the pharmaceutical product.

What makes retatrutide a triple agonist?

A single retatrutide peptide carries agonist activity at three receptors: the GIP receptor, the glucagon-like peptide 1 receptor and the glucagon receptor. Tirzepatide covers the first two, and semaglutide covers only the GLP-1 receptor. Adding glucagon receptor activity is the structural difference that earns retatrutide the triple agonist label in the published literature.

Is cagrilintide a GLP-1 receptor agonist?

No. Cagrilintide is a long-acting amylin analog. It acts on the amylin receptors, which are complexes of the calcitonin receptor with a receptor activity-modifying protein, and on the calcitonin receptor itself. Those belong to the calcitonin peptide family, not the incretin family, so cagrilintide does not bind the GLP-1, GIP or glucagon receptors that semaglutide, tirzepatide and retatrutide target.

How does cagrilintide compare with semaglutide or tirzepatide?

They are different receptor classes. Semaglutide is a single GLP-1 receptor agonist and tirzepatide is a dual GIP and GLP-1 receptor agonist, both in the incretin family. Cagrilintide is an amylin analog acting through calcitonin receptor and RAMP complexes. Because the receptor systems do not overlap, cagrilintide has been studied both alone and co-administered with semaglutide as CagriSema.

For in vitro research use only. Not for human consumption. Not evaluated by the FDA. Not intended to diagnose, treat, cure, or prevent any condition. This article summarizes published research and is not medical advice.