GLPwatch
Design of a novel long-acting dual GLP-1/GIP receptor agonist.
Bioorg Med Chem · 2024
Last updated 2026-05-28Researchers developed a new long-acting drug called D314 that targets both GLP-1 and GIP receptors, similar to tirzepatide. In mouse studies, D314 lowered blood sugar and reduced body weight as effectively as tirzepatide. In dogs, D314 had a half-life of about 78 hours, suggesting it could be given once a week in humans. The study suggests D314 may be a potential treatment for type 2 diabetes and obesity.
AI summary of the abstract below.
| Journal | Bioorg Med Chem, 2024 |
|---|---|
| Citations | 3 |
| Relative citation ratio | 0.65 |
| NIH percentile | 36 |
| Molecules | — |
| Conditions studied | Type 2 Diabetes, Obesity |
Abstract
Tirzepatide, the first approved dual GLP-1/GIP receptor agonist (RA), has achieved better clinical outcomes than other GLP-1RAs. However, it is an imbalanced dual GIP/GLP-1 RA, and it remains unclear whether the degree of imbalance is optimal. Here, we present a novel long-acting dual GLP-1/GIP RA that exhibits better activity than tirzepatide toward GLP-1R. A candidate conjugate, D314, identified via peptide design, synthesis, conjugation, and experimentation, was evaluated using chronic studies in db/db and diet induced obese (DIO) mice. D314 achieved favorable blood glucose and body weight-lowering effects, equal to those of tirzepatide. Its half-life in dogs (T: 78.3 ± 14.01 h) reveals its suitability for once-weekly administration in humans. This preclinical study suggests the potential role of D314 as an effective agent for treating T2DM and obesity.
Verbatim abstract via PubMed 38330849 ↗