Research notes
Differences between dual and triple hormone receptor agonist designs in published studies
The two classes are close relatives. This page sets out where the published descriptions of LY3298176, a dual agonist, and LY3437943, a triple agonist, differ and where they do not. It is about molecular design and receptor set, not about effects or use.
The receptor set is the defining difference
A dual agonist in this class is described as acting at the GIP receptor and the GLP-1 receptor. A triple agonist adds the glucagon receptor. Everything else on this page is secondary to that: the classification in the literature is by which receptors the compound activates in cell-based assays, and a compound is placed in one class or the other on that basis alone.
Where the designs are alike
Both LY3298176 and LY3437943 are described in their primary papers as 39-residue single-chain peptides whose backbone is derived from the GIP sequence rather than from GLP-1 or glucagon. Both carry a fatty diacid side chain attached through a linker to a lysine residue, and both use aminoisobutyric acid substitutions, including at the position where the native incretins are cleaved by dipeptidyl peptidase-4. A reader comparing the two sequences finds most of the chain in common.
Where they differ
The residue substitutions that produce glucagon receptor activity in LY3437943 are the substantive difference, and the primary paper reports which positions were changed and the effect of each on potency at each receptor. Both compounds are described with a C20 fatty diacid side chain; the lysine it is attached to is given in each paper. The balance of potency across the receptors, reported as EC50 ratios, is a design target chosen during each programme and differs between the two.
Published studies of both compounds in humans exist and are cited on the product pages as work by others. Their findings concern investigational medicines, not the laboratory material sold here, and are not described on this site.
LY3298176 research peptide · LY3437943 research peptide
A note on naming
Glucagon is not an incretin. A triple agonist is therefore not a triple incretin agonist; the accurate phrase is a GIP, GLP-1 and glucagon receptor agonist, or a triple-hormone receptor agonist. The literature uses both.
Primary literature
Listed so a reader can go to the source. These papers describe the compounds as studied by others; they are not claims about any material sold here.
- Coskun T, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept Molecular Metabolism, 2018
- Coskun T, 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 Metabolism, 2022