What is GEP44? A GLP-1/PYY explainer

GEP44 is not a brand name and not an approved medicine. It is a laboratory code for an experimental peptide that fuses pieces of three molecules the body already makes: GLP-1, the GLP-1 receptor agonist exendin-4, and the gut hormone peptide YY3-36. A July 2026 review in Frontiers in Endocrinology lays out why researchers built it that way: the goal is a single molecule that pushes on GLP-1 receptors and peptide YY receptors at once, in the hope of matching the weight loss seen with drugs like tirzepatide and retatrutide while cutting the nausea and vomiting that make people quit those drugs^[1].

What GEP44 actually is

The molecule was first described by Milliken, Borner, Doyle and colleagues in the Journal of Medicinal Chemistry in 2021. It is a single, monomeric chimeric peptide, meaning it is one chain rather than two drugs mixed in a vial, built from a GLP-1 receptor agonist segment (based on exendin-4) fused to a peptide YY3-36 segment. That structure lets it act on the GLP-1 receptor and on multiple neuropeptide Y receptors, chiefly Y1 and Y2, in the same dose^[2]. Peptide YY is a hormone the gut releases after meals that signals fullness through the Y2 receptor, and pairing that signal with GLP-1 is the mechanistic bet behind the whole programme. Every result described below comes from rats, mice and a small carnivorous mammal called a musk shrew that pharmacologists use specifically because it can vomit, which most lab rodents cannot.

The preclinical numbers so far

In diet-induced obese rats, five daily doses of GEP44 produced measurable weight loss within days, and 28-day dosing at 50 nmol per kg produced body-weight reductions in the range of 12% to 16% depending on sex, a rodent-scale figure well short of the weight loss reported in human trials of retatrutide and tirzepatide, and not directly comparable to them^[1]. A separate line of work in diet-induced obese mice tested whether those effects depend on the GLP-1 receptor by repeating the experiment in mice bred without it. GEP44 lowered energy intake and body weight in normal mice at several doses, and that effect disappeared in the GLP-1-receptor knockout animals, which is the kind of control that tells researchers a drug is doing what its name says^[3]. On the glycaemic side, fasting blood glucose fell by roughly 11% in treated rats and by 30% to 35% in treated mice, and glucose tolerance testing showed a clearer improvement than the comparator drug exendin-4^[2].

Why the side-effect story is the actual pitch

Gastrointestinal side effects are the reason a meaningful share of patients stop GLP-1-class drugs, and the recent Phase 3 data for retatrutide put a number on it: trial discontinuations for adverse events ran as high as 11.3% on the top dose, driven mostly by nausea, diarrhoea and vomiting. The GEP44 case rests on the musk shrew emesis model, where the original 2021 paper reported vomiting in only one of eight shrews given GEP44 at two different doses, against vomiting in five of eight shrews given a low dose of exendin-4^[2]. The rats also showed no pica, the compulsive consumption of a non-food substance like kaolin clay that researchers use as a proxy for nausea in animals that cannot vomit or report feeling sick. Better tolerability in a handful of animal studies is a real finding, but it is a finding about animals, not a finding about the people who currently manage GI side effects on tirzepatide or watch for them ahead of any future retatrutide approval.

What this is not

GEP44 has not been given to a single human volunteer in a published clinical trial. The Frontiers review states plainly that no clinical trials have assessed its effect on food intake or blood glucose in patients^[1]. In April 2026, a small biotech, SureNano Science, announced plans to run FDA-pathway toxicology and pharmacology studies for GEP-44 as a step toward filing for Investigational New Drug status, with an eye toward a first-in-human trial application in Australia^[4]. That announcement describes planned studies, not a completed IND filing or an approved trial, and it carries the standard forward-looking-statement caveats that apply to any small public company describing work still ahead of it. Nothing about GEP44 is currently prescribable in the way tirzepatide is, regulated, or dosed in a way that translates to a human recommendation, and the animal doses reported in the papers above describe what researchers gave lab animals for research purposes, not a human treatment protocol.

Where this sits next to the drugs already on the market

Tirzepatide is an approved, prescribed dual GIP and GLP-1 agonist. Retatrutide is a triple agonist in late-stage human trials with a defined Phase 3 programme and a 2029 outcomes readout. GEP44 sits a full stage earlier than either: a mechanism with encouraging rodent and shrew data, and a company-stated intention to start the regulatory groundwork for human testing. Readers tracking the incretin field can follow the retatrutide regulation pages and the tirzepatide page for the compounds that already have a human safety record, and we will update this page if GEP44 files an actual IND or dosing begins in people.

This article is for educational and journalistic purposes only and does not constitute medical advice. GEP44 is an investigational compound with no marketing authorisation or approved use anywhere. PeptideMethods.com does not sell, distribute, or facilitate the sale of any peptide product, and no dosing information here is a recommendation for human use.