Age Old Arthritis Drug may Lower Sugar Levels in Type 2 Diabetic patients

Highlights

• Leflunomide, a common anti-rheumatoid arthritis drug could be an effective new therapy for lowering blood glucose levels in patients with type-2 diabetes.
• Leflunomide has long been approved to treat rheumatoid arthritis.
• After taking the medication, leflunomide not only normalized blood glucose levels, but also caused cells to start responding to insulin again.

Leflunomide, a common anti-rheumatoid arthritis drug may help lower blood glucose levels in type 2 Diabetes patients, finds a new study. The findings of this study are published in the Journal of Endocrinology. The anti-inflammatory drug, Leflunomide, 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, Leflunomide, 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 Leflunomide 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 leflunomide treatment on blood sugar levels of two different type 2 diabetes mouse models. In both models, leflunomide not only normalized blood glucose levels, but also caused cells to start responding to insulin again.

"We studied how leflunomide works at a molecular level and found that it targets a protein involved in desensitizing the insulin receptor, which is responsible for instructing the cells to start absorbing sugar from the bloodstream", says Professor Xiulong Xu.

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However, leflunomide 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 Leflunomide's effect on the insulin receptor, studied here. "We know some inflammatory factors can also desensitize the insulin receptor, and Leflunomide 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 Leflunomide also occurs in humans as well as mice.

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Reference

1. Junhong Chen, Jing Sun, Michelle E Doscas, Jin Ye, Ashley J Williamson, Yanchun Li, Yi Li, Richard A Prinz, Xiulong Xu. Control of hyperglycemia in male mice by leflunomide: mechanisms of action, Journal of Endocrinology (2018).doi: 10.1530/JOE-17-0536

Source-Eurekalert