GLPwatch
Design of Xenopus GLP-1-Based Long-Acting Dual GLP-1/Y<sub>2</sub> Receptor Agonists.
J Med Chem · 2022
Last updated 2026-05-28Researchers designed a new peptide that activates both GLP-1 and Y2 receptors, combining the effects of two drugs into one. In mice with obesity or type 2 diabetes, this dual agonist improved blood sugar control and reduced body weight more than single-receptor drugs. In mice with liver fat buildup, it also lowered harmful fat levels in the liver and reversed liver fat accumulation better than a GLP-1-only drug (liraglutide).
AI summary of the abstract below.
| Journal | J Med Chem, 2022 |
|---|---|
| Citations | 12 |
| Relative citation ratio | 1.11 |
| NIH percentile | 54 |
| Molecules | — |
| Conditions studied | Type 2 Diabetes, Obesity |
Abstract
GLP-1 receptor (GLP-1R) and neuropeptide Y receptor (YR) dual agonists have shown great potential to treat obesity and type 2 diabetes (T2DM). We developed a multitarget strategy to design monomeric agonists based on GLP-1 (xGLP-1) and PYY analogues with dual activation activities on GLP-1R and YR. A novel peptide, , was obtained via stepwise structure optimization and receptor screens. In / and diet-induced obesity (DIO) mice, produced greater effects on long-term glycemic control and body weight reduction than GLP-1R and YR monoagonist counterparts. Notably, in high-fat diet-induced nonalcoholic steatohepatitis (NASH) mice, treatment significantly reduced hepatic triglyceride and total cholesterol levels and reversed hepatic steatosis compared with GLP-1R monoagonist (liraglutide) treatment. Collectively, these data support the therapeutic potential of our GLP-1R/YR dual agonist as a novel antidiabetic, antiobesity, and antisteatotic agent.
Verbatim abstract via PubMed 36214844 ↗