A common rheumatoid arthritis treatment may be an effective new therapy for lowering blood glucose levels of patients with type-2 diabetes, according to a study published in the Journal of Endocrinology. The anti-inflammatory drug, lefluonamide, lowered blood glucose levels and reversed insulin resistance in mouse models of type 2 diabetes, which suggests that this therapy could be repurposed as an effective antidiabetic treatment, particularly suitable for patients with both diabetes and rheumatoid arthritis.
Rheumatoid arthritis, affecting approximately 1% of the worldwide population, is a chronic autoimmune condition that causes pain and swelling in the joints. The anti-inflammatory drug, lefluonamide, has long been approved to treat the condition and previous clinical studies have noted that patients taking the drug tended to have lower blood glucose levels and that obese patients lost weight. Type 2 diabetes is a growing health concern, affecting 1 in 11 adults worldwide, and is primarily caused by poor diet, obesity and an inactive lifestyle. In this metabolic disorder, cells do not respond to the hormone insulin, which causes patients to have high blood sugar levels that can lead to serious complications, including heart disease and kidney problems. In addition to controlling lifestyle factors, many patients require drug therapy to correct their blood glucose levels and prevent disease progression. Although previous findings indicated that lefluonamide may have desirable antidiabetic effects, the mechanisms behind these observations had never been fully investigated, nor had its effectiveness as an antidiabetic drug been tested.
In this study, Prof Xuilong Xu and colleagues, at the Institute of Comparative Medicine at Yangzhou University, investigated the effects of lefluonomide treatment on blood sugar levels of two different type 2 diabetes mouse models. In both models lefluonomide not only normalised blood glucose levels, but also caused cells to start responding to insulin again.
"We studied how lefluonomide works at a molecular level, and found that it targets a protein involved in desensitising the insulin receptor, which is responsible for instructing the cells to start absorbing sugar from the bloodstream", says Professor Xiulong Xu.
However, lefluonomide also acts on other molecular targets in the body. This suggests that more studies are needed to confirm that the anti-diabetic effects observed are solely caused by lefluonamide's effect on the insulin receptor, studied here. "We know some inflammatory factors can also desensitise the insulin receptor, and lefluonamide is an anti-inflammatory, so it may be that it controls blood sugar partly by its anti-inflammatory effect." Professor Xu adds.
The next step for Professor Xu's group is to conduct clinical trials to test if the antidiabetic effect of lefluonamide also occurs in humans as well as mice.