Researchers have found that a class of older antipsychotic drugs could be a promising new therapeutic option for people with Type 2 diabetes, helping fill a need among patients who aren’t able to take other currently available treatments.
“There is a growing need to find new therapies for Type 2 diabetes,” said John Ussher, professor in the Faculty of Pharmacy & Pharmaceutical Sciences, and lead author of the recent study published in the journal Diabetes.
As Ussher explained, the drug metformin is one of the most common therapeutics for Type 2 diabetes, but about 15 percent of patients aren’t able to take it. Another type of commonly used drug class (insulin secretagogues) to treat diabetes isn’t as effective for later-stage patients, who also need a different option.
“For the patients who can’t take metformin, patients with late-stage diabetes where their beta cells aren’t working as well, when you’re trying to find new therapies or new combination therapies as the disease progresses, it becomes more important to find new drug classes that target new mechanisms, so then you have more options to try and lower blood sugar in those individuals,” Ussher explained.
The mechanism Ussher and his team turned their attention to is succinyl CoA:3-ketoacid CoA transferase (SCOT), an enzyme involved in the body’s process of making energy from ketones. They used computer modelling to find drugs that could potentially interact with SCOT and landed on an older generation of antipsychotic drugs, a class called diphenylbutylpiperidines, or DPBP for short.
Ussher and his team had previously found that a specific drug within this class called pimozide could be repurposed to help treat diabetes, but they’ve since expanded their focus to see whether more of the DPBP class could also be useful for treating the disease.
“We’ve tested three drugs now, and they all interact with this enzyme,” said Ussher. “They all improve blood sugar control by preventing the muscle from burning ketones as a fuel source. We believe this SCOT inhibition is the reason these antipsychotics might actually have a second life for repurposing as an anti-diabetic agent. For us, the excitement is that it looks like the entire family of these compounds interacts with this protein and can improve blood sugar control in Type 2 diabetes,” he added.