Novel GLP-1/Glucagon Dual Agonist Protects Kidneys From Fibrosis and Lasts 2-3x Longer Than Semaglutide
A new GLP-1/glucagon co-agonist peptide called 1907-B had 2-3x longer half-life than semaglutide and outperformed it in protecting against kidney fibrosis in both diabetic and non-diabetic mouse models.
Quick Facts
What This Study Found
1907-B had 2-3x longer half-life than semaglutide in rats and monkeys, and outperformed semaglutide and glucagon individually in reducing kidney fibrosis in both diabetic (db/db) and non-diabetic (UUO) CKD models through dual GLP-1R/GCGR signaling.
Key Numbers
GLP-1R and GCGR expression was lower in CKD mouse kidneys and correlated with disease severity. Receptor knockdown worsened kidney injury in both db/db and UUO models.
How They Did This
GLP-1R/GCGR expression analysis in CKD kidneys. Receptor knockdown studies (genetic and pharmacological). Novel peptide design and characterization. Pharmacokinetic studies in rats and cynomolgus monkeys. Efficacy testing in db/db diabetic nephropathy and UUO kidney fibrosis models. Loss-of-function validation.
Why This Research Matters
CKD affects ~850 million people globally with limited treatment options. A dual agonist that protects kidneys in both diabetic and non-diabetic settings — and lasts longer than current GLP-1 drugs — could transform kidney disease treatment.
The Bigger Picture
While GLP-1 drugs are known to protect kidneys, this study demonstrates that dual GLP-1/glucagon activation provides superior protection. The finding that kidney disease itself reduces GLP-1R and GCGR expression explains why replacement therapy works and suggests a new paradigm: dual receptor activation as a comprehensive kidney-protective strategy.
What This Study Doesn't Tell Us
Mouse models of CKD may not fully replicate human disease. Glucagon receptor activation could theoretically raise blood sugar in non-diabetic patients, though this was not observed. Clinical pharmacokinetics and safety in humans need testing. Manufacturing an ultralong-acting dual agonist peptide may present challenges.
Questions This Raises
- ?Will 1907-B advance to human clinical trials for CKD?
- ?Does the ultralong half-life translate to less frequent dosing than current weekly GLP-1 drugs?
- ?Would dual agonism cause hyperglycemia through glucagon receptor activation in non-diabetic CKD patients?
Trust & Context
- Key Stat:
- 2-3x longer than semaglutide 1907-B dual agonist lasts significantly longer and outperforms semaglutide for kidney fibrosis protection in preclinical models
- Evidence Grade:
- Moderate evidence: comprehensive preclinical study with multiple animal models, genetic validation, and cross-species PK data, but no human clinical data.
- Study Age:
- Published in 2024 in Acta Pharmaceutica Sinica B. Represents a novel approach to kidney disease treatment.
- Original Title:
- Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis.
- Published In:
- Acta pharmaceutica Sinica. B, 14(3), 1283-1301 (2024)
- Authors:
- Zhao, Qian(2), Dong, Jiale, Liu, Han(2), Chen, Hui, Yu, Huan, Ye, Shuyin, Yu, Shuangjin, Li, Yu, Qiu, Longhui, Song, Nazi, Xu, Hongjiao, Liu, Qi, Luo, Zhiteng, Li, Yuyi, Wang, Rui, Chen, Guodong, Jiang, Xianxing
- Database ID:
- RPEP-09669
Evidence Hierarchy
Frequently Asked Questions
How is 1907-B different from semaglutide?
1907-B activates both GLP-1 and glucagon receptors (semaglutide only activates GLP-1), stays in the body 2-3 times longer, and showed superior kidney protection in animal studies. The dual activation appears to provide kidney benefits that neither receptor alone can achieve.
Could this help people with kidney disease?
The preclinical results are very promising — 1907-B protected kidneys in both diabetic and non-diabetic CKD models, outperforming the current best GLP-1 drug. However, human clinical trials are needed before it could become available as a treatment.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-09669APA
Zhao, Qian; Dong, Jiale; Liu, Han; Chen, Hui; Yu, Huan; Ye, Shuyin; Yu, Shuangjin; Li, Yu; Qiu, Longhui; Song, Nazi; Xu, Hongjiao; Liu, Qi; Luo, Zhiteng; Li, Yuyi; Wang, Rui; Chen, Guodong; Jiang, Xianxing. (2024). Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis.. Acta pharmaceutica Sinica. B, 14(3), 1283-1301. https://doi.org/10.1016/j.apsb.2023.11.020
MLA
Zhao, Qian, et al. "Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis.." Acta pharmaceutica Sinica. B, 2024. https://doi.org/10.1016/j.apsb.2023.11.020
RethinkPeptides
RethinkPeptides Research Database. "Design and discovery of a highly potent ultralong-acting GLP..." RPEP-09669. Retrieved from https://rethinkpeptides.com/research/zhao-2024-design-and-discovery-of
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.