LY3437943 is one of several engineered peptides studied for combined activity at the GLP-1, GIP and glucagon receptors, a research direction sometimes called the "multi-receptor incretin agonist" category. It sits alongside survodutide (BI 456906), mazdutide (IBI362, also designated LY3305677) and cotadutide (MEDI0382), three dual-receptor agonists studied in separate sponsor research programs. Each molecule was engineered from a different peptide backbone and has been examined in a distinct set of published preclinical and clinical studies. This article summarizes how the four compare on receptor target, structural scaffold and acylation chemistry, framed as study design and endpoints rather than as a ranking of outcomes.
| Compound | Receptor profile studied | Backbone / scaffold origin | Status in published literature |
|---|---|---|---|
| LY3437943 (LY3437943) | GLP-1, GIP and glucagon receptor triple agonist | GIP-derived sequence engineered for added GLP-1 and glucagon receptor affinity | Discovery paper, phase 1b dose-escalation trial, phase 2 and phase 3 trial literature |
| Survodutide (BI 456906) | GLP-1 and glucagon receptor dual agonist | Oxyntomodulin-derived peptide backbone, fatty-acid acylated | Discovery/preclinical pharmacology paper, phase 1 and phase 2 trials including liver-disease cohorts |
| Mazdutide (IBI362 / LY3305677) | GLP-1 and glucagon receptor dual agonist | Oxyntomodulin-derived backbone, fatty-acid acylated | Phase 1b and phase 2 trials in Chinese research cohorts, phase 3 trial protocol published |
| Cotadutide (MEDI0382) | GLP-1 and glucagon receptor dual agonist, GLP-1-biased in published pharmacology | Oxyntomodulin-derived peptide backbone, acylated for extended exposure | Phase 2a and phase 2 mechanistic trial literature; sponsor discontinued further clinical development |
Where does LY3437943 fit among these multi-receptor research peptides?
LY3437943 is the only one of the four engineered to engage all three receptors, GLP-1, GIP and glucagon, at once, built from a GIP receptor-selective backbone modified to add balanced GLP-1 and glucagon receptor agonism (Coskun et al., 2022). Survodutide, mazdutide and cotadutide are each dual agonists engineered for combined GLP-1 and glucagon receptor activity without the added GIP component. For the pharmacology behind LY3437943's own three-receptor engagement, see how LY3437943 engages GLP-1, GIP and glucagon receptors. A separate comparison against two single/dual-receptor incretin peptides already in wide research use is covered in LY3437943 vs LY3298176 vs NN9535, which this article does not repeat.
How do the receptor profiles differ among the three glucagon-receptor dual agonists?
Although survodutide, mazdutide and cotadutide are all described as GLP-1/glucagon dual agonists, the published pharmacology characterizes each with a different relative balance between the two receptors. The preclinical paper on survodutide describes an engagement profile selected for robust activity at both receptors in rodent assays (Zimmermann et al., 2022). Cotadutide's pharmacology has been described in the clinical literature as GLP-1-receptor-biased, with a reported in vitro potency ratio favoring GLP-1 over glucagon (Parker et al., 2020). Mazdutide's phase 1b and phase 2 publications describe a similar dual-receptor mechanism examined through metabolic and safety endpoints in Chinese research cohorts, without reporting an identical potency ratio to the other two (Ji et al., 2022; Ji et al., 2023). Researchers comparing across this group treat the specific receptor balance, not just the receptor list, as the variable that differentiates downstream signaling in cell-based assays.
How do the structural scaffolds compare: GIP-derived versus oxyntomodulin-derived backbones?
A key structural distinction in this group is the peptide backbone each molecule was built from. LY3437943's sequence derives from a GIP receptor-selective scaffold modified with substitutions intended to add GLP-1 and glucagon receptor affinity (Coskun et al., 2022). Survodutide, mazdutide and cotadutide instead trace their backbones to oxyntomodulin, a native peptide with some intrinsic GLP-1 and glucagon receptor activity, which each program then modified and acylated for stability and selectivity (Zimmermann et al., 2022; Ambery et al., 2018). This split, a GIP-derived scaffold for the triple agonist versus oxyntomodulin-derived scaffolds for the three dual agonists, is why the structure-activity literature treats LY3437943 as a distinct design rather than "cotadutide plus a GIP substitution."
What do acylation chemistry and the preclinical record show?
All four peptides are fatty-acid acylated, a modification that promotes albumin binding and extends circulating exposure relative to the unmodified native peptides each is derived from. The specific diacid chemistry and attachment site differ by molecule and are detailed in each compound's own discovery or pharmacokinetic publication rather than in this comparison. Preclinical depth also differs: the LY3437943 discovery paper combined receptor-activation assays, rodent pharmacology and an early clinical dataset in one publication (Coskun et al., 2022), and the survodutide paper similarly characterized receptor pharmacology and metabolic endpoints in diet-induced obese rodent models before any human data (Zimmermann et al., 2022). Mazdutide's and cotadutide's earliest published data instead begin at the clinical stage, with phase 1b dose-ranging studies reporting safety and pharmacodynamic measures directly in human research cohorts (Ji et al., 2022; Ambery et al., 2018). Readers working specifically with LY3437943's own structural and pharmacokinetic data should see what is LY3437943 rather than relying on cross-compound generalizations here.
What have the clinical trials measured, and why did cotadutide's program stop?
Mazdutide progressed from the phase 1b dataset to a published phase 2 randomized controlled trial measuring metabolic and body-composition endpoints in adults with overweight or obesity (Ji et al., 2022; Ji et al., 2023). Survodutide's clinical literature includes a phase 1 study in participants with cirrhosis measuring pharmacokinetics and tolerability in a population with altered hepatic clearance (Lawitz et al., 2024), reflecting a research interest in liver-disease populations distinct from the other three compounds. Cotadutide's record includes a phase 2a ascending-dose study (Ambery et al., 2018) and a mechanistic follow-up examining glucose-lowering pathways across dose cohorts (Parker et al., 2020), but the sponsor subsequently discontinued further clinical development; it is included here as a completed, closed research program rather than an active candidate.
Were there earlier triple-agonist research tool compounds before LY3437943?
Before any clinically developed triple agonist existed, pharmacology groups had already published proof-of-concept peptides combining GLP-1, GIP and glucagon receptor activity in a single molecule as research tools, used to establish that balanced tri-agonism was achievable in rodent metabolic models. LY3437943's discovery paper situates the molecule within this line of unimolecular multi-agonist design work, describing how the engineering approach used for earlier tool peptides was adapted to produce a candidate suitable for clinical-stage study (Coskun et al., 2022). Those early tool compounds are generally not sold or supplied as standardized research-grade material and are referenced here only for pharmacological context.
What does this comparison mean for a lab working primarily with LY3437943?
The practical value of this comparison is reading LY3437943's own published data in context rather than substituting another compound's findings for it. A triple-receptor design, a GIP-derived backbone and a specific acylation chemistry mean that results reported for survodutide, mazdutide or cotadutide should not be assumed to generalize to LY3437943, and the reverse is equally true. Lot-specific identity and purity data for research-grade LY3437943 are posted on our LY3437943 product page, the reference point for confirming what a given vial contains before it is used in any assay.
Frequently asked questions
Is survodutide the same molecule as LY3437943?
No. Survodutide (BI 456906) is a GLP-1/glucagon dual agonist built from an oxyntomodulin-derived backbone. LY3437943 (LY3437943) is a GLP-1/GIP/glucagon triple agonist built from a GIP-derived backbone. The two molecules are structurally distinct and are studied in separate research programs.
Is cotadutide still being studied in active clinical trials?
Published records show cotadutide (MEDI0382) completed phase 2a and phase 2 mechanistic trials, but its sponsor discontinued further clinical development. The published literature on cotadutide is a closed, completed dataset rather than an ongoing program.
What distinguishes mazdutide from the other dual agonists in this comparison?
Mazdutide (IBI362/LY3305677) has been studied primarily in Chinese research cohorts through phase 1b and phase 2 randomized trials, with a phase 3 trial protocol subsequently published. Its backbone and receptor profile parallel survodutide's and cotadutide's dual GLP-1/glucagon agonism, though the specific engineering and trial populations differ.
Why do survodutide, mazdutide and cotadutide share an oxyntomodulin-derived origin while LY3437943 does not?
Oxyntomodulin is a native peptide with intrinsic, if modest, activity at both the GLP-1 and glucagon receptors, which made it a logical starting scaffold for engineering a dual agonist. LY3437943's designers instead started from a GIP receptor-selective peptide and added GLP-1 and glucagon receptor affinity through additional substitutions, a different engineering route to a related pharmacological goal.
Are any of these four compounds approved for human use?
No. As described in the cited literature, all four are investigational molecules studied in preclinical and clinical research settings. None of them is an approved drug, and nothing in this article describes a protocol for use in any subject.
Where can a researcher read more about LY3437943's own structure and pharmacology specifically?
See what is LY3437943 for an overview of its design, and how LY3437943 engages GLP-1, GIP and glucagon receptors for the receptor-level pharmacology this comparison references.
References
- Coskun T, Urva S, Roell WC, 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. PubMed 35985340.
- Urva S, Coskun T, Loh MT, et al. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet. 2022;400(10366):1869-1881. PubMed 36354040.
- Zimmermann T, Thomas L, Baader-Pagler T, et al. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Mol Metab. 2022;66:101633. PubMed 36356832.
- Lawitz EJ, Fraessdorf M, Neff GW, et al. Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis. J Hepatol. 2024;81(5):837-846. PubMed 38857788.
- Ji L, Gao L, Jiang H, et al. Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. EClinicalMedicine. 2022;54:101691. PubMed 36247927.
- Ji L, Jiang H, Cheng Z, et al. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nat Commun. 2023;14(1):8289. PubMed 38092790.
- Ambery P, Parker VE, Stumvoll M, et al. MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. Lancet. 2018;391(10140):2607-2618. PubMed 29945727.
- Parker VER, Robertson D, Wang T, et al. Efficacy, Safety, and Mechanistic Insights of Cotadutide, a Dual Receptor Glucagon-Like Peptide-1 and Glucagon Agonist. J Clin Endocrinol Metab. 2020;105(3):dgz047. PubMed 31608926.
Research use only. Homegrown Peptides products are for laboratory research and are not for human or animal use. Nothing in this article is medical advice.
