Asthma Drug Shows Promise in Controlling Blood Glucose in Diabetes
Amlexanox may alter genes that improve blood glucose control in patients with type 2 diabetes.
Findings from a new clinical trial published by Cell Metabolism suggest that a repurposed asthma drug may be able to lower blood glucose levels among certain patients with type 2 diabetes.
The authors found that patients with a certain molecular signature responded to treatment with amlexanox, an anti-inflammatory drug that treats asthma.
“When we looked at the drug-treated group we saw a bimodal distribution, that is, there were some responders and some non-responders,” said lead researcher Alan Saltiel, PhD. “We didn’t understand why, so we did a molecular analysis from biopsies of fat cells we took from patients at the beginning and end of the study.”
While additional studies are needed, the investigators believe that the asthma drug could be used by certain patients with diabetes.
“In the responder group, the level of inflammation in fat was higher than in the non-responder group at the beginning of the study, indicating that there is something about inflammation that predisposes a person to respond,” Dr Saltiel said. “And, what was really amazing was that there were more than 1,100 gene changes that occurred exclusively in the responders.”
Amlexanox inhibits the IKKε and TBK1 enzymes. The team of researchers previously discovered that the enzymes are expressed in mice with obesity, resulting in a drop in calories burned. These findings caused the authors to screen more than 150,000 chemicals for inhibitors.
In mice studies, the investigators found that amlexanox treatment caused obese mice to lose weight. The therapy also increased the mice’s sensitivity to insulin, and improved diabetes symptoms and fatty liver disease, according to the study.
In humans, the investigators observed similar gene changes to mice treated with the drug. These genetic changes were found to reduce blood glucose levels.
The preliminary study included 6 patients to confirm the safety of amlexanox in patients with type 2 diabetes. It was followed by a clinical trial of 42 patients with obesity and type 2 diabetes who were randomized 1:1 to receive placebo or amlexanox for 3 months.
The authors measured blood glucose levels, insulin sensitivity, weight, and liver fat. They also biopsied fat cells from the patients’ abdomens at baseline and after treatment to track gene expression, according to the study.
“The most exciting part of this is that we have a new drug that has never been studied before,” Dr Saltiel said. “It’s a new mechanism for a diabetes and fatty liver drug. It’s promising, but there are a lot of questions that need to be answered still.”
The investigators found that one-third of patients responded to amlexanox and that patients with nonalcoholic fatty liver experienced disease improvements.
The team of researchers plan to conduct follow-up studies to determine which gene changes are the most important, which affect liver fat, which result in lower blood glucose levels, and more, according to the study. A new human clinical trial is currently being planned.
“We’re planning a new study to look at whether we can stratify patients who are likely to respond based on the degree of underlying inflammation,” Dr Saltiel concluded. “A second study will look at a combination with another drug that we think will be particularly effective."