Two-pronged type 2 diabetes (T2D) treatment is more effective when the medications are linked by a heat-sensitive tether rather than simply concurrently administered, according to a new study published in Science Advances.
T2D is a progressive disease in which tissue becomes resistant to insulin, meaning that the movement of sugar from the bloodstream into cells cannot be regulated. There are many treatment options for T2D, however, a single drug is usually not able to treat advanced cases. Additionally, medications tend to lose potency over time and often cause weight gain, which itself can promote insulin resistance and exacerbate the disease.
Researchers looked at the peptide-based drugs glucagon-like peptide-1 (GLP-1) and fibroblast growth factor 21 (FGF21) using a mice model. The drugs were linked using an elastin-like polypeptide (ELP) that is injected beneath the skin. The ELP slowly dissolves and releases the GLP-1 and FG21 over time.
The study found that the effects from the linked drugs last longer than 1 week with a single injection. The linked approach had several advantages, such as a single molecule being more predictable in how it moves through the body. It also reduced the medication burden by simplifying the treatment regime. The approval process is also significantly more straight forward than a mixture, according to the study.
"Linking the drugs to an ELP allows us to design a compound that is liquid at room temperature but forms a gel-like depot upon injection…The depot dissolves over the course of at least a week, slowly and regularly releasing drug to the system over time," Caslin Gilroy, PhD, postdoctoral scholar at the University of California, Berkeley, said in the press release.
GLP-1 is a short peptide, whereas FGF21 is a large folded protein, making the 2 drugs very different compounds. However, they both still worked well together when combined into 1 dose, which means this method can potentially be applied to therapies beyond diabetes, according to the study authors.
Tethering together type 2 diabetes drugs increases efficacy of combination therapy (Press Releae), Durhman, NC, August 26, 2020, ScienceDaily, Accessed September 2, 2020