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.
2-3x longer than semaglutide1907-B dual agonist lasts significantly longer and outperforms semaglutide for kidney fibrosis protection in preclinical models
What the researchers 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.
Why it 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 numbers in context
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 the study worked
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.
Who was studied
Diabetic (db/db) and non-diabetic (UUO) CKD mouse models
What this study cannot 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.
How to read the evidence
Moderate evidence: comprehensive preclinical study with multiple animal models, genetic validation, and cross-species PK data, but no human clinical data.
When this study was published
Published in 2024 in Acta Pharmaceutica Sinica B. Represents a novel approach to 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.
Questions still open
- 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?
Common questions
How is 1907-B different from semaglutide?
Could this help people with kidney disease?
Read the original research
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
Citation
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