Retatrutid (GLP-3) 10mg

▎GLP-3 Structure

▎Molecular Background

Research Progress

Ding, Mingling and colleagues compared GLP-1, GLP-2, and GLP-3 in HK-2 cells and in murine unilateral ureteral obstruction (UUO) and aging models. Integrating the in vivo and in vitro data, the authors reported model- and compound-specific patterns in fibrosis- and inflammation-related endpoints. In the UUO model, GLP-1-associated changes were linked to PI3K-AKT inhibition, GLP-2-associated changes to PI3K-AKT inhibition and PPAR pathway activation, and GLP-3-associated changes to concurrent inhibition of PI3K-AKT and NF-κB pathways. In the aging model, all three compounds were associated with changes in G2/M arrest-related measures. At the doses tested, the authors reported the largest overall changes in the GLP-3 group within the models studied.[1]

Fig1. Renal measurements reported in the UUO mouse model comparing GLP-1, GLP-2, and GLP-3.[1]

(A) Schematic diagram of the UUO model experiment.

(B) Comparison of kidney size and morphology among the five groups under natural light.

(C) Kidney weight-to-body weight ratio.

(D) Diastolic blood pressure (DBP).

(E) Urinary potassium (K+) concentration.

(F) Serum uric acid (UA) level.

(G) Blood urea nitrogen (BUN) level.

(H) Serum creatinine (CRE) level. Data are represented as mean ± SEM, significant differences were determined by one way ANOVA followed by Tukey’s post hoc test; n = 6, n, the number of independent biological replicates; ∗p < 0.05.

Jonas Petersen and colleagues studied the combination of cagrilintide with GLP-3 in diet-induced obese male rats. Daily co-administration produced dose-dependent differences in body weight and food intake that were greater than those reported for the corresponding monotherapies and matched-dose comparator combinations containing GLP-1 or GLP-2. The authors also measured circulating cholesterol, triglycerides, and insulin. Pair-feeding and weight-matched experiments were used to distinguish food-intake- and body-weight-associated effects from other molecular responses. Plasma proteomic analysis identified enrichment of bioenergetic processes, while brain transcriptomic analysis identified neuronal programs associated with energy-balance regulation under the experimental conditions.[2]

Fig2. Proposed signaling pathways examined for GLP-3 in isolated mouse atrial preparations.[3]

The source figure summarizes receptor and signaling components considered in the isolated mouse atrial study, including GCGR, GLP-1R, GIPR, cAMP, PKA, phosphodiesterase activity, muscarinic and adenosine receptor signaling, and proteins involved in calcium handling. Antagonists and inhibitors shown in the figure were used by the authors to examine pathway contributions under the experimental conditions.[3]

Neumann, Joachim and colleagues examined GLP-3 in isolated left and right atrial preparations from adult CD1 mice. At 100 nM, GLP-3 did not increase force of contraction in electrically driven left atrial preparations, whereas positive chronotropic responses were observed in spontaneously beating right atrial preparations. The authors reported potentiation of the right-atrial response by rolipram and attenuation by the GCGR antagonist adomeglivant and the PKA inhibitor H89. Additional antagonist experiments involving propranolol, carbachol, atropine, PIA, and DPCPX were used to investigate cAMP- and receptor-associated signaling. These findings were generated in isolated mouse atrial tissue rather than in an in vivo model.[3]

Greta Karoline Viebahn and colleagues established a 31-day diet-induced steatohepatitis mouse model using a Western diet, fructose and sucrose in drinking water, and a terminal fructose challenge. A separate experiment also examined the response to a single fructose challenge. The investigators measured body weight, plasma ALT, hepatic triglycerides and cholesterol, histological changes, inflammatory markers, and liver gene-expression profiles. In female mice receiving GLP-3 during the final 2 weeks of the 31-day model, the authors reported differences in body weight, ALT, hepatic lipid measurements, and inflammation-related endpoints compared with vehicle-treated animals. The study also reported sex-dependent differences in the response to the acute fructose challenge.[4]

Fig3. Measurements reported after a single fructose challenge in female mice in the Viebahn et al. study.[4]

The source figure shows the acute fructose-challenge design together with liver weight, body weight, liver-to-body-weight ratio, plasma ALT, hepatic triglycerides, and representative histological staining. Group sizes, timing, statistical methods, and complete experimental details are reported in the original publication.[4]

Ulya Keskin and colleagues investigated GLP-3 in a streptozotocin-induced, insulin-deficient diabetes model in male Sprague-Dawley rats. Animals were assigned to control, streptozotocin, streptozotocin plus GLP-3, or GLP-3-only groups. Spatial learning and memory were assessed using the Morris water maze and passive avoidance tests, while metabolic measurements, hippocampal IL-1β and TNF-α, BDNF, CREB and AKT mRNA expression, Tau protein levels, and cortical and hippocampal histology were evaluated. Streptozotocin exposure produced persistent hyperglycemia, body-weight loss, and behavioral changes. In GLP-3-treated diabetic rats, the authors reported lower blood glucose, preserved overall Morris water-maze performance relative to untreated diabetic rats, and only limited, task-dependent attenuation of the short-term passive-avoidance deficit. They also reported lower hippocampal TNF-α and partial preservation of cortical and hippocampal cellular architecture. GLP-3 alone did not improve behavioral performance beyond the control group under the study conditions.[5]

Research Limitations

The studies summarized above use HK-2 cells, isolated mouse atrial tissue, and several rodent disease or dietary models. Results from these systems are not directly interchangeable. Differences in species, tissue preparation, model induction, exposure schedule, comparator compounds, and measured endpoints can influence the observations reported. Findings from these preclinical systems therefore should remain tied to the specific model and study conditions in which they were generated.[1-5]

The current literature also includes direct GLP-3 studies and comparative studies involving GLP-1, GLP-2, or cagrilintide. Results from combination studies cannot be attributed to GLP-3 alone, and comparative differences at a particular experimental dose do not establish superiority outside that model. PubChem currently maintains GLP-3 as an annotated reference record without assigning the reference record a direct compound CID; related substance or structure records should therefore not be treated as interchangeable with a specific research material without appropriate analytical characterization.

COCER Peptides presents GLP-3 solely for laboratory research and analytical use. It is not intended for human or veterinary use. The research described above summarizes findings reported in third-party publications and does not represent a claim regarding the clinical performance, safety, efficacy, diagnosis, treatment, prevention, or approved use of any COCER Peptides material.

▎Relevant Citations

References

[1] Ding M, Li X, Wei Y, et al. Comparative effects of semaglutide GLP-2 and GLP-3 on renal fibrosis in UUO and aged mice[J]. iScience, 2026,29(9):117174.

DOI:10.1016/j.isci.2026.117174.

[2] Petersen J, Merrild C, Holm S K, et al. Cagrilintide and GLP-3 combination therapy enhances weight loss and metabolic outcomes in obese male rats[J]. Nature Diabetes, 2026.

DOI:10.1038/s42255-026-01603-y.

[3] Neumann J, Ahlrep U, Hofmann B, et al. Contractile effects of GLP-3 in isolated mouse atrial preparations[J]. Naunyn-Schmiedeberg's Archives of Pharmacology, 2025,398(12):17147-17160.

DOI:10.1007/s00210-025-04335-0.

[4] Viebahn G K, Khurana A, Freund L, et al. Retatrutide improves steatohepatitis in an accelerated mouse model of diet-induced steatohepatitis with a fructose binge[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2025,329(6):G680-G695.

DOI:10.1152/ajpgi.00164.2025.

[5] Keskin U, Altın E, Kara M K, et al. Effects of GLP-3 on learning and memory in streptozotocin-induced male diabetic rats[J]. Behavioural Brain Research, 2026,514:116343.

DOI:10.1016/j.bbr.2026.116343.

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