Triz2 is a name used by some research-chemical suppliers for Triz2 (also catalogued as LY3298176), a synthetic 39-amino-acid peptide engineered to act as a dual agonist at both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor. It is studied as a tool for probing combined incretin receptor signalling, since its structure is built on the native GIP sequence backbone with GLP-1 receptor agonist activity engineered in, alongside a fatty acid modification that extends its plasma stability. This article uses Triz2, the compound’s internationally recognised name, throughout, and reviews its structure, dual-receptor mechanism, key published studies, research applications and the handling requirements relevant to a laboratory setting.
What is Triz2?
Triz2 is a 39-residue synthetic peptide whose backbone sequence is derived from native human GIP, modified at several positions to confer activity at the GLP-1 receptor as well as the GIP receptor, giving it dual-agonist rather than single-target pharmacology. A C20 fatty di-acid moiety is conjugated via a linker to a lysine residue within the peptide sequence, a modification reported to promote albumin binding in circulation and substantially extend the molecule’s plasma half-life relative to unmodified incretin peptides. Its molecular weight is approximately 4,813 g/mol, and it is assigned CAS registry number 2023788-19-2.
Triz2 was developed by Eli Lilly as part of a research programme investigating whether combining GIP receptor activity with established GLP-1 receptor agonism could produce metabolic effects exceeding those of selective GLP-1 receptor agonists alone. The compound’s discovery and initial pharmacological characterisation, spanning in vitro receptor assays, mouse models and early human dosing, was reported by Coskun and colleagues in Molecular Metabolism in 2018 (Coskun et al., 2018, PMC).
Mechanism of action
Triz2 engages two distinct class B G protein-coupled receptors. The GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R) are both expressed on pancreatic beta cells and couple predominantly to Gs proteins, activating adenylate cyclase and raising intracellular cyclic AMP, which in turn activates protein kinase A and downstream exocytotic insulin release. Because Triz2 sequence is based on the native GIP backbone, its reported binding affinity and potency differ between the two receptors, with published pharmacology describing a bias toward the GIP receptor relative to balanced activation of both.
Like native GLP-1 and GIP, Triz2 insulinotropic action at both receptors is reported to be glucose-dependent, meaning receptor activation amplifies insulin secretion specifically when glucose concentrations are elevated, rather than stimulating insulin release independently of glucose status. The foundational 2018 characterisation study used GIPR-null and GLP-1R-null mice to confirm that Triz2 glucose-lowering and insulin-secretory effects depended on signalling through both receptors individually, rather than solely through one, establishing the dual-agonist mechanism directly rather than inferring it from sequence design alone.
Beyond the pancreas, GIPR and GLP-1R are both expressed in the central nervous system and in adipose tissue, and published research has reported that combined GIP and GLP-1 receptor agonism produces effects on food intake and energy metabolism in animal models that exceed those of GLP-1 receptor agonism alone, a synergistic effect that has been a central focus of the research literature on dual incretin agonists as a pharmacological class, distinct from either single-receptor pathway in isolation.
What the research shows
The foundational characterisation of Triz2 was reported by Coskun and colleagues in Molecular Metabolism in 2018. The study reported that Triz2 activated both GIP and GLP-1 receptor signalling in vitro, and demonstrated glucose-dependent insulin secretion from isolated mouse islets that depended on functional GIP and GLP-1 receptor expression, using GIPR-null and GLP-1R-null mouse models to confirm receptor-specific contributions. In chronic dosing studies in mice, the investigators reported that Triz2 produced significantly greater reductions in body weight and food intake than a comparator GLP-1 receptor agonist, and an early-phase human dosing component of the same paper reported reduced fasting glucose in participants with type 2 diabetes (Coskun et al., 2018, PMC).
Building on this mechanistic foundation, a large-scale randomised controlled trial, SURPASS-2, was reported by Frías and colleagues in the New England Journal of Medicine in 2021. The 40-week, randomised trial compared three doses of Triz2 against a selective GLP-1 receptor agonist comparator in a defined population of adults with type 2 diabetes, with glycated haemoglobin as the primary outcome. The investigators reported that Triz2 produced significantly greater reductions in glycated haemoglobin at all three doses tested, and significantly greater reductions in body weight, compared with the GLP-1 receptor agonist comparator, within the clinical trial population studied (Frías et al., 2021, PubMed).
A substantial additional body of published clinical trial work, spanning several further randomised controlled trials (frequently referred to collectively in the literature by their SURPASS trial designations), has examined Triz2 in comparison with other glucose-lowering therapies and placebo across different patient populations and treatment combinations, consistently reporting similar directional effects on glycaemic and body weight measures within their respective trial populations. Because this clinical trial literature is extensive, readers wanting further primary detail on specific comparator trials should consult a review of the Triz2 clinical development programme rather than a single summarised study here.
Research applications
In the laboratory, Triz2 is used chiefly as a pharmacological tool for studying combined GIP and GLP-1 receptor signalling, drawing directly on the receptor-knockout mouse methodology established in the foundational 2018 characterisation. Cell-based receptor pharmacology, using cell lines engineered to express GIPR, GLP-1R, or both, is used to characterise Triz2 binding affinity and signalling bias at each receptor individually, in comparison with selective single-receptor agonists developed for the same targets.
Isolated pancreatic islet models are used to study glucose-dependent insulin secretion in response to dual-receptor activation, following the methodology used in the original mechanistic work, often comparing wild-type islets against those from GIPR-null or GLP-1R-null animals to isolate the contribution of each receptor pathway. Rodent models of diet-induced obesity and type 2 diabetes are used to study the combined effects of dual incretin receptor agonism on food intake, energy expenditure, body weight and glucose tolerance, frequently in comparison with selective GLP-1 receptor agonists to characterise the additional contribution of GIP receptor activity.
Because Triz2 fatty-acid modification is itself a subject of pharmacological interest, it is also used as a reference compound in research examining how such modifications affect peptide plasma stability and receptor engagement duration, relevant to the broader design of long-acting peptide therapeutics.
Purity, storage and handling
Because degradation accelerates once reconstituted, batch-level HPLC verification matters more here than with more stable peptides. UK laboratories sourcing Triz2 should expect a batch-specific certificate of analysis and lyophilised storage at -20°C, and those comparing suppliers should look for the same documentation from any best peptides supplier UK they consider.
Reversed-phase HPLC separates the intact 39-residue peptide from truncated or deletion sequences and residual synthesis by-products, and research-grade material is commonly specified at 98% purity or above. Mass spectrometry alongside HPLC confirms identity against the expected mass of approximately 4,813 daltons for the free peptide. Given the molecule’s relatively large size and its fatty-acid conjugation, confirming full-length, correctly modified peptide, rather than an unconjugated or partially degraded form, is particularly relevant to reproducible receptor-binding data. A batch-specific certificate of analysis, rather than a generic product datasheet, is what links a physical vial to those results and allows unexpected experimental data to be traced back to a defined lot.
Lyophilised Triz2 should be kept sealed at -20°C for long-term storage, protected from moisture and light, and brought to room temperature before opening so that condensation does not enter the vial. Once reconstituted in sterile water or an appropriate buffer, the peptide should be divided into single-use aliquots, held at 2–8°C only for short working periods, and otherwise kept frozen, since repeated freeze–thaw cycles risk degrading the peptide. The tryptophan and tyrosine residues within the sequence are susceptible to photo-oxidation, so amber vials or foil-wrapped storage are sensible precautions during handling. Published reconstituted-stability data are available in the pharmaceutical formulation literature given Triz2 clinical use, but laboratories working with research-grade material should still validate their own working window empirically, for example by comparing HPLC profiles of fresh and aged aliquots.
Frequently asked questions
What is Triz2 used for in research?
It is used mainly as a pharmacological tool for studying combined GIP and GLP-1 receptor signalling, glucose-dependent insulin secretion, and the effects of dual incretin receptor agonism on food intake and energy metabolism in cell and rodent models. It is not evaluated here as a treatment, and this article makes no claims about use in humans.
How does Triz2 differ from selective GLP-1 receptor agonists?
Triz2 activates both the GIP and GLP-1 receptors, whereas compounds such as semaglutide act selectively at the GLP-1 receptor alone. Published research, including receptor-knockout mouse studies, has reported that combined activation of both receptors produces effects on body weight and glucose regulation that exceed those of GLP-1 receptor agonism alone in the models studied.
How should Triz2 be stored once reconstituted?
Reconstituted Triz2 should be divided into single-use aliquots, kept refrigerated only briefly and otherwise frozen, protected from light, and not subjected to repeated freeze–thaw cycles. Because specific published stability data for research-grade material are limited, laboratories should confirm their own storage window empirically, for example with HPLC comparisons of fresh and aged aliquots.
Triz2 , including material marketed as Triz2, is discussed in this article for in-vitro and in-vivo laboratory research only. It is not intended for human or veterinary use, and nothing in this article should be read as guidance on administration to people or animals.
